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Fluid Resuscitation and Fluid Resuscitation and Massive TransfusionMassive Transfusion
Dalhousie Critical Care Lecture Series
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ICUOutline
Kinetics of fluid therapy Colloids vs Crystalloids What do we use?
Sepsis Trauma Peri-operative
Massive Transfusion Complications of Resuscitation Case Examples
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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
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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)]
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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
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ICUDistribution of Different Fluids
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ICUColloids vs Crystalloids
Still no firm data either way SAFE study has clarified some
questions In burns colloids safe as soon as 6
hours
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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.
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ICUCrystalloids
Balanced = electrolyte solution similar to ECF and contains buffer
Example = LR or Normosol R Separate category = NS
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ICUWhat’s in this stuff?
Ringers lactate Normal Saline Pentaspan Normosol R
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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
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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
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ICUFluid in Sepsis Resuscitation
EGDT Strategy When?
• 1hr
• 6hr EGD
• How Much? • 1.5L more fluid
• Goal directed therapy reduced mortality by 17%!
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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
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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
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ICU
…but no difference in need for renal replacement therapy
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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
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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
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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
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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.
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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
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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.
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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
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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 #.
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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!
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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
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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 !
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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
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ICU
Blood Component Therapy
Whole blood is not available in Canada except Autologous Donation
Options include:1. pRBC2. Plasma3. Cryoprecipitate4. Platelets5. Factor VIIa
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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
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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
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ICUThrombocytopeniaThrombocytopenia
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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
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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)
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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)
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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
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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
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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
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ICU
Complications of Blood Transfusion
Infectious Immunologic Fluid overload/pulmonary edema Transfusion reactions TRALI
(transfusion related acute lung injury)
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ICUTransfusion ReactionsTransfusion Reactions
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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
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ICUInfection
Hepatitis B,C etc HIV West Nile Virus CMV Bacterial
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ICU
Infection Risk (blood Infection Risk (blood products)products)
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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!
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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
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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?
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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
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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
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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
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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