Fluid Resuscitation and Fluid Resuscitation and Massive TransfusionMassive Transfusion

Dalhousie Critical Care Lecture Series

ICUOutline

Kinetics of fluid therapy Colloids vs Crystalloids What do we use?

Sepsis Trauma Peri-operative

Massive Transfusion Complications of Resuscitation Case Examples

ICUPhysiology

Total body water = 60% of body weight In a 70 kg man = 0.6 X 70 = 42L Distributed

Intracellular (425 ml/kg or 2/3) Extracellular (175 ml/kg or 1/3)

Extracellular

Plasma volume

Interstitial fluid

Transcellular fluid

Modified from Miller, 2000

ICU

The Extracellular Compartment

Divided into the interstitial and the intravascular

Low pressure in the intravascular is hypotension

Resuscitation of the intravascular space is what feeds the rest of the compartments Qv = Kf [(Pc – Pi) – δc(πc – πi)]

ICUWhat does it mean?

Net volume of fluid crossing capillary membrane

Reflection coefficient = membrane permeability

Ranges from 0 (completely permeable) to 1 (impermeable)

What you administer determines distribution

from T,J. Gan ASA refresher course 2003

ICUDistribution of Different Fluids

ICUColloids vs Crystalloids

Still no firm data either way SAFE study has clarified some

questions In burns colloids safe as soon as 6

hours

ICUSAFE Study

RCT enrolled 6997 patients requiring ICU admit Randomized to albumin/NS Outcomes at 28 days similar But trend toward ↑ mortality in albumin/head

trauma 460 patients Mortality higher in albumin group 33.2% vs. 20.4 saline

group Saline or Albumin for Fluid Resuscitation in Patients with

Traumatic Brain InjuryN Engl J Med 2007;357:874-84. And mortality with albumin/septic shock

N= 1218 patients Relative risk of death reduced in albumin group 0.87

p=0.06SAFE study investigators NEJM 2004;350:2247-2256.

ICUCrystalloids

Balanced = electrolyte solution similar to ECF and contains buffer

Example = LR or Normosol R Separate category = NS

ICUWhat’s in this stuff?

Ringers lactate Normal Saline Pentaspan Normosol R

ICU

Content

LR NS Normosol Pentaspan

Na+ 130 154 140 154

K+ 4.0 0 5.0 0

Cl- 109 154 98 154

pH 6.7 5.7 7.4 5.4

Buffer Lactate - Acetate/gluconate

-

osmo 273 308 295 326

ICUTiming of Resuscitation

A Cochrane review compared early vs delayed resuscitation.

Increased risk of dying in early group Should we keep the BP low in this

group? Goal-directed therapy see Rivers et

al

Kwan et al Cochrane Review 2003

ICUFluid in Sepsis Resuscitation

EGDT Strategy When?

• 1hr

• 6hr EGD

• How Much? • 1.5L more fluid

• Goal directed therapy reduced mortality by 17%!

ICUCrystalloids vs Colloids in Sepsis

Both seem to work equally in restoring hemodynamics

More volume required with crystalloids Lower reflection coefficient for colloids and

therefore more sustained hemodynamic effect as it tends to stay in the intravascular space

May “plug the holes” in vascular leak syndrome

Less interstitial edema

ICUCrystalloids vs Colloids in Sepsis

Nothing is free though: Colloids are more expensive Albumin is a pooled blood product May deposit where they are not wanted

Skin – pruritis Kidneys

osmotic damage to proximal tubules described in multiple settings

Clinically can be seen as decreased renal function in at risk populations

Schortgen F, Lacherade JC, Bruneel F, et al:Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: A multicentre randomised study. Lancet 2001; 357:911–916

ICU

…but no difference in need for renal replacement therapy

ICU

Summary of Resuscitation in Sepsis

Fluid is good Crystalloid resuscitation is safe Colloids look good but need a large

RCT to prove it The role of blood is still unknown

ICUTrauma

Conventional wisdom espoused by ATLS is 2L of crystalloids followed by PRBC to restoration of normal heart rate and BP

Controversies Type of crystalloid Permissive hypotension Hypertonic crystalloids Colloids

ICU

Blood loss (mL)Blood loss (mL) > 750> 750 750 - 1500750 - 1500 1500 - 20001500 - 2000 > 2000> 2000

Blood loss (% Blood loss (% total)total)

> 15%> 15% 15 - 30%15 - 30% 30 - 40%30 - 40% > 40%> 40%

Pulse ratePulse rate < 100< 100 > 100> 100 > 120> 120 > 140> 140

Blood pressureBlood pressure NormalNormal NormalNormal ↓↓ ↓↓

Pulse pressurePulse pressure Normal or Normal or ↑↑ ↓↓ ↓↓ ↓↓

OrthostasisOrthostasis AbsentAbsent MinimalMinimal MarkedMarked MarkedMarked

Capillary refillCapillary refill NormalNormal DelayedDelayed DelayedDelayed DelayedDelayed

Resp rateResp rate 14 - 2014 - 20 20 - 3020 - 30 30 - 4030 - 40 > 34> 34

UO (mL/hr)UO (mL/hr) > 30> 30 20 - 3020 - 30 5 - 155 - 15 < 5< 5

CNS mental CNS mental statusstatus

Slight anxietySlight anxiety Mild anxietyMild anxiety Anxious/Anxious/confusedconfused

Confused/Confused/lethargiclethargic

CI (L/min)CI (L/min) ↓ ↓ 0-10%0-10% ↓↓ 20-50%20-50% ↓↓ 50-75%50-75% ↓↓ >75%>75%

Class I ClassII Class III Class I ClassII Class III Class IVClass IV

Clinical Correlates of HemorrhageClinical Correlates of Hemorrhage

American College of Surgeons, 1989

ICUHypertonic SalineHypertonic Saline

250 mL of 7.5% saline = 2-3 L of 0.9% saline

Has been evaluated with 8 RCT Improved rates of survival in 7, but

only statistical significance only achieved in 1

Meta-analysis demonstrated improved survival rates, especially in head trauma (38% versus 27%)

Wade CE, Kramer GC, Grady JJ, et al. Efficacy of hypertonic 7.5% saline and6%dextran-70 in treating trauma: a meta-analysis of controlled clinical studies. Surgery 1997;122:609–16.

ICU

Summary of Resuscitation in Trauma

In the absence of traumatic brain injury permissive hypotension with BP>80, good pulses and alert patient is reasonable prior to definitive surgical management

Ringers lactate is the recommended crystalloid Hypertonic saline may be the way to go but is not

yet the standard of care Blood is still the best

O negative immediately available Type specific in ~10 minutes Cross and Type ~ 60 minutes

ICU

Summary of Resuscitation in Trauma

Transfusion of blood components in the setting of hypotension and ongoing bleeding should be empiric and not wait for coagulopathy to develop. Especially in the setting of massive transfusion (~10u PRBC)

FFP:PRBC should be around 1:1 Platlets may be targeted to counts, but are

generally needed after 10u PRBC. If greater than 6 units of blood have been given

with evidence of microvascular bleeding consider coagulation adjuncts such as VIIa.

ICUPeri-op Fluids

How much is too much? Recent study in Annals of Surgery Two groups of patients undergoing colon

surgery:1. Third space loss replaced (standard)2. Third space loss not replaced

(restricted) Group 2 less CV/RESP/Wound

complications

Brandstrup, B etal Ann Surg 2003; 238:641-648

ICUPeri-op Fluids

Review of recent study by Kabon Anesthes. Analg. 2005 showed no reduction in infection with liberal fluid administration.

Venn in 2002 found vigorous hydration hospital stay and # of post-op complications in Femur #.

ICUType and Screen

Blood is ABO-Rh typed & screened for common antibodies

99.8% chance of compatibility for type 99.94% with antibody screen 99.95% with crossmatch Many institutions do not X-match blood Type specific blood available < 10 minutes!

ICUBlood Product Availability

6 units type 0 pRBC in ER Give Rh- blood to women of reproductive

age Type specific blood 5 to 10 minutes Plasma 45 minutes Cryoprecipitate, platelets in 10 minutes

ICU

Estimated Blood Volume (EBV)

65 to 70 ml/kg In 70 kg man total blood volume

= 5L Remember in 50 kg female 50 X 0.7 = 3.5L !

ICUMassive Transfusion

No strict definition Accepted = transfusion of > 1 blood

volume Recall our 70 kg patient EBV = 5 L lost or 10-12 units pRBC

transfused

ICU

Blood Component Therapy

Whole blood is not available in Canada except Autologous Donation

Options include:1. pRBC2. Plasma3. Cryoprecipitate4. Platelets5. Factor VIIa

ICUPacked Cells

Hematocrit 0.70 Volume = 300 ml NS, LR, Normosol, Plasma

acceptable diluents Stored in CPDA /ADsol at QEII

(citrate phosphate dextrose adenine) citrate binds calcium

All pRBC in Canada leukocyte reduced

ICUPlatelets

Indicated when platelet count < 75,000 SITUATION SPECIFIC…!

One unit should increase platelet count by 10,000 Order: 1 bag=4 “old” units Ensure proper filter used for transfusion

Transfusion time important

Rarely required < 15 units pRBC …??? High risk of TRALI

ICUThrombocytopeniaThrombocytopenia

ICUPlasma

Rich in coagulation factors EXCEPT factor V and VIII WHY?

Fibrinogen content low in plasma Available in 500 ml aliquots

1L = 4 units 10% increase CF 30 to 45 minutes to process and thaw After 5 units pRBC consider 1:1

plasma and pRBC

ICUActivated factor VII

Derived from hamster kidney cell line Binds exposed tissue factor

generates small amt. of thrombin activates platelets amplifies thrombin production

Very expensive No evidence that improves outcome

(too early in use)

ICUActivated Factor VII

Good review in Critical Care Medicine 2005 33:883-890

Factor VIIa now used in liver disease/Tx, decreases # of packed cells transfused

Surgery prostatectomy eliminated pRBC in treatment group (60% of placebo were transfused)

Trauma RCT underway (QEII part of study)

ICUCryoprecipitate

Rich in factor VIII, fibrinogen (I), XIII, vWF Comes in “units” usually 8 at a time for the replacement of fibrinogen, vWF

treatment of uremic bleeding in appropriate circumstances,

treatment and prevention of severe factor XIII deficiency.

DIC MASSIVE TRANSFUSION

ICU

Complications of Crystalloid Fluid Resuscitation

Hypothermia calcium, magnesium (Dilutional) Coagulopathy

Dilutional Consumptive Hypothermia Hypocalcemia

Acidosis non-anion gap MA Confusion with anion gap MA

Edema

ICU

Complications of Colloid Resuscitation

Fluid overload Coagulopathy

Dilutional and direct factor VIIIR:Ag and VIIIR:RCo theoretically after 2L

probably overstated

Platelet aggregation problems

ICU

Complications of Blood Transfusion

Infectious Immunologic Fluid overload/pulmonary edema Transfusion reactions TRALI

(transfusion related acute lung injury)

ICUTransfusion ReactionsTransfusion Reactions

ICUTRALI

Noncardiogenic pulmonary edema Immune reaction between donor

WBC and recipient plasma Onset 1-2 hours post transfusion RX ETT and diuresis Recovery in 96 hours Second leading cause of death in

transfusion

Miller et al. Miller’s Anesthesia 2005

ICUInfection

Hepatitis B,C etc HIV West Nile Virus CMV Bacterial

ICU

Infection Risk (blood Infection Risk (blood products)products)

ICUInfection Risk (US 2006)

HIV 1/2.1 million HCV 1/1.9 million HBV 1/220,000

Don’t forget others- bacterial, syphilis, CJD

ICUImmunologic

Immunomodulation and downregulation are important

Occurs at many levels Affects both T and B cell activity Improves transplant graft survival but

↑ metastases inpatients with cancer

ICUFluid in the Critically Ill

After restoration of normal hemodynamics many patients in the ICU require large amounts of ongoing fluid support

The crystalloid vs colloid debate persists in this population

TRICC trial SAFE trial

ICUTransfusion Trigger

Bernard et al TRICC trial Only applies to patients < 65 y.o. In ICU setting Excludes patients with acute

coronary syndrome (ACS) ? Application in trauma/resuscitation

ICUTRICC Trial

838 critically ill patients with euvolemia randomized to transfusion trigger of 70 or 100

Same 30-day mortaIity Improved mortality in restrictive strategy

for some subgroups patients <55 APACHE<20

ICUAlbumin Replacement

In critically ill patients with albumin <30 randomized to replacement vs no replacement ie not as volume resuscitation

Albumin level was higher in the treatment arm (31 vs 22)

Organ function in respiratory, cardiovascular and central nervous system improved more in the albumin group after 7 days p=0.026

ICUARDS

Fluid strategies in ARDS are different b/c there are overt drawbacks to over resuscitation

RCT of restrictive fluid strategy improves mortality 25.% vs 28.4%

Comparison of Two Fluid-Management Strategies in Acute Lung Injury N Engl J Med 2006;354:2564-75.

25% Albumin plus lasix vs lasix alone improves oxygenation in ARDS patients

A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury Crit Care Med 2005 Vol. 33, No. 8

ICUHow Much Fluid to Give?

Most agree the danger lies in under resuscitation during initial resuscitation

15% of intravascular volume can be loss without changes in HR, BP, CO but splanchnic volume is reduced by 40%

Patients with abnormal gut perfusion do worse than those who have normal measurements

Mythen MG, Webb AR: Intra-operative gut mucosal hypoperfusion is associated with increased post-operative complications and cost. Intensive Care Med 20:99 - 104, 1994

ICU Acute Pancreatitis

Massive third space loss Distributive hemodynamics 2° to

SIRS Major mortality (50%) from ARF

requiring dialysis Once patient adequately

resuscitated with volume then consider vasopressors

ICUPancreatitis

Consider resuscitation with LR or Normosol if urine output present

NS also adequate if large volumes (>4 to 5 L) avoided

Ensure adequate Hb (i.e. > 70) Beware the secondary compartment

syndrome from resuscitation!

ICUHow Much Fluid?

During the initial resuscitation it is more straightforward

Restoration of normal blood pressure and heart rate

Markers of end organ perfusion Consciousness Skin color Urine output Lactate, ScVO2

ICUHow Much Fluid?

It gets more confusing when the patient becomes “wet” from vascular leak syndrome.

Although they may look like this…they may still be intravascularly deplete

How can you tell if the patient would still benefit from fluid?

ICUHow Much Fluid?

JVP, CVP, PAW do not predict fluid responsiveness

Osman D, Ridel C, Ray P, et al. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med 2007;35:64–68.

Family of curves: depending on ventricular function changes the meaning of an absolute number

ICUHow Much Fluid?

Much written about changes in arterial waveform during respiratory cycle Spontaneous vs positive pressure

ventilation Low versus high volume ventilation Lung compliance Changes in BP versus slope of the curve

But as always, the best solution is also the most ridiculously simple

ICUHow Much Fluid?

Response to intrinsic fluid bolus by raising the legs

Monnet X, Rienzo M, Osman D, et al. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med 2006; 34:1402–1407.

Boulain T, Achard JM, Teboul JL, et al. Changes in BP induced by passive leg raising predict response to fluid loading in critically ill patients. Chest 2002; 121:1245–1252.

Changes in aortic blood flow with 450

leg elevation was equivalent to that seen with a 500ml crystalloid fluid challenge

ICUSummary

There are pros and cons of crystalloids and colloids

Choice of one over the other is based upon the patient’s physiology

Determination of a patient’s fluid status can be difficult and we often overestimate the intravascular volume

Amount of fluid and fluid choice has an important impact on patient outcome