IV FLUIDS IN INTENSIVE CARE

Vineel Bezawada MBBS MS.

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

BODY FLUIDS

In 1861,

Thomas Graham's investigations on diffusion

classified substances as crystalloids or colloids based on their ability to

diffuse through a parchment membrane.

Crystalloids passed readily through the membrane,

whereas colloids did not. ( Greek word - glue)

IV fluids are similarly classified based on their ability to pass through barriers separating body fluid compartments,

i.e intravascular and extravascular

(interstitial) fluid compartments

History

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.

CRYSTALLOIDS

adds 275 mL to the plasma volume

and 825 mL to the

interstitial volume

Note : the total volume expansion (1100 mL)

slightly greater than the infused volume.

This is the result of a fluid shift from the ICF to extracellular space,

because isotonic saline is actually hypertonic to the Plasma

infusion of 1 L of 0.9% Nacl

Dextgm/dl

Na K Cl Acet Lact NH4Cl

Ca Mg HPO4

Citr Mosm/lt

5%D

50 - - - - - - - - - - 278

0.9% NS

- 154 - 154 - - - - - - - 308

5%D,0.45% NS

50 77 - 77 - - - - - - - 432

DNS 50 154 - 154 - - - - - - - 586RL - 130 4 109 - 28 - 3 - - - 274Isolyte-G

50 63 17 150 - - 70 - - - - 580

Isolyte-M

50 40 35 40 20 - - - - 15 - 410

Isolyte-P

50 25 20 22 23 - - - - 3 3 368

Isolyte-E

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

CRYSTALLOIDS

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.

ISOTONIC SALINE(0.9% NaCl )

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.

Disadvantages

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.

LACTATED RINGER'S

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

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

Advantages

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.)

Disadvantages

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.

DEXTROSE SOLUTIONS (5%,10%,25%,50%)

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.

Disadvantages

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.

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)

Disadvantages

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.

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.

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

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,

20% albumin solution

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).

Complications

Safety of ALBUMIN

Design: Systematic review of randomised controlled trials comparing albumin or plasma protein fraction or crystalloid solution in critically ill patients

Subjects: 30 randomised controlled trials including 1419 randomised patients.

Main outcome measure: Mortality from all causes

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

Results:

For hypovolaemia the relative risk of death after albumin

administration was 1.46 (95% confidence interval 0.97 to 2.22)

for burns the relative risk was 2.40 (1.11 to 5.19) for hypoalbuminaemia it was 1.69 (1.07 to 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 17 critically ill patients treated with albumin there is one additional death.

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

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

No Increased mortality with Albumin

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

SAFE STUDY

Albumin is safe

Vincent et al, Morbidity in hospitalised patients receiving Albumin,

a metaanalysis of RCTs,

Crit.Care.Med,2004;32

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

Current Evidence

Hydroxyethyl starch preparations (HES)

Amylopectin - rapidly hydrolysed

- renally excreted

Hydroxyethyl groups: - @ C2&C6

metabolic

Degradation

Stored in RES.

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)

HES

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

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

HETASTARCH

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

Features

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

Disadvantages of HES

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

PE NTA ST ARC H

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)

Gelatins

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 )

THE DEXTRANS

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

Disadvantages

COMPOSITION OF COLLOIDSColloid Vol.

Effect(%)

Mol Wt (kDa)

Osm (mOsm/kg)

COP

pH Duration of action

(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 3.5-6.5

18-24

Gelofusine 80 22.6 274 40 7.2 2-3

Haemaccel 140 35 302 35 7.3 48

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

HEXTEND

RESUSCITATION COLLOID or CRYSTALLOID

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

CRYSTALLOID ORIGINS

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]

COLLOID PERFORMANCE

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.

EXPENSE

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

Comparative costs of parenteral fluids

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

EDEMA

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

SURVIVAL Benefit ?

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

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)

HYPERTONIC RESUSCITATIONEvidence ?

RESUSCITATION

in

SEPSIS

Intravascular volume depletion

Peripheral vasodilation with hypotension

Abnormal distribution of blood flow

SEPSIS Pathophysiology

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

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

Early Goal-Directed Therapy (EGDT)

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.

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.

choice of IVF crystalloid or colloid

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

Normal saline in SEPSIS

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 ?

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.

Normal saline induced hyperchloremia 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.

COLLOIDS 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.

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

for every 17 critically ill patients treated with albumin there is one additional death.

Albumin in sepsis

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

ALBUMIN in 21st Century

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.

Favorable Futere for Albumin? Suggestion of SAFE study

Intern Emerg Med. 2006;1(3):243-5.Human albumin solution for resuscitation and volume expansion in

critically ill patients. Meta analysisLiberati 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.

Can we use Albumin ?Recent Metaanalysis

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 resuscitate Patients in Septic shock

1 L N/S 15-20 minutes1 L Ringers 30 minutes

Start Norepinephrine if MAP < 70 mm Hg

1 L Hextend/Hespan 30-40 minutes1 L Ringers 30-40 minutes1 L Hextend/Hespan 30-40 minutesRingers lactate 200cc/hBolus 500cc Hextend/Hespan as required

Irwin and Rippe's Intensive Care Medicine, 6th Edition©2008

Suggested Fluid Resuscitation Algorithm for Hemodynamic Instability of

Severe Sepsis and Septic Shock

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.

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

Hypertonic saline (7.5%)

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.

Complications of massive transfusion of crystalloids or colloids

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

Damage Control Resuscitation

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.

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

Process of Damage Control Resuscitation

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.

rFVIIa in Hemorrhagic sock

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.

Optimal fluid in Hemorrhagic shock

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 µL, 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 µL, 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

◦ Hypotensive from blood loss (SBP <90 mm Hg) ◦ Have a base deficit >-6 ◦ Hypothermic ( <96°F) ◦ 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

Indications for 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.

Guidelines for administration of rFVIIa

Best IV Fluid for Rsuscitation in ICU

Optimal IV Fluids for SHOCK in ICU

HYPOVOLEMIA :

CRYSTALLOIDS

SEPSIS :

CRYSTALLOIDS & COLLOIDS

HEMORRHAGE :

CRYSTALLOIDS, FWB