Transcript Massive blood transfusion

Massive blood transfusion
Mohammad Faranoush ,MD
Associate Professor
Rasool Akram Medical Center
All bleeding eventually stops
Epidemiology of Massive Transfusion
• Massive transfusion accounts for 3-5% of civilian
and 8-10% of military trauma, but has a 30-60%
mortality
• Uncontrolled hemorrhage = most common cause of
preventable early death
• Resuscitation with crystalloids/colloids or
plasma-poor red cell concentrates causes
dilutional coagulopathy
• Conducting a massive transfusion is a COMPLEX
medical procedure
• Health care professionals and hospitals remain ill-prepared
for such an event
INTRODUCTION
• Massive transfusion, defined as the replacement by
transfusion of more than 50 percent of a patient's blood
volume in 12 to 24 hours, may be associated with a
number of hemostatic and metabolic complications
• Massive transfusion involves the selection of the
appropriate amounts and types of blood components to
be administered, and requires consideration of a
number of issues including volume status, tissue
oxygenation, management of bleeding and coagulation
abnormalities, as well as changes in ionized calcium,
potassium, and acid-base balance.
What is a “Massive Transfusion”
• Replacement of one blood mass, or 10 units
of RBCs in a 24 hour period
• Dynamic Definitions
• Transfusion of ≥4 PRBC units with 1 hour when
ongoing need is foreseeable
• Replacement of 50% of the total blood volume within 34 hours
Challenges inherent to the
management of severe bleeding
• Complex medical scenarios
• High mortality
• Consistently identified weaknesses
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Poor planning
Poor communication
Infrequent laboratory monitoring
Significant delay in ordering/administering plasma
Failure to prevent hypothermia & low use of fluid
warmers
• Early reliance on cryoprecipitate and rescue medications
Massive Transfusion Protocols
• Purpose of an MTP:
• To improve relevant clinical outcomes
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Formalization of an institutional plan or SOP
Facilitate/protocolize communication
Ensure frequent laboratory monitoring
Reduce delay in ordering and administering blood
products
• Deliver a reasonable ratio of plasma to red blood cells
(FP:RBC)
Are Massive Transfusion Protocols
Evidence-informed?
• Riskinet al, 2009
– Mortality rate -45% before MTP implemented-19% postimplementation
– Improved communication
– Better systems flow and optimize blood product availability
Protocol
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Code Omega
Physician order sheet
Hourly blood work
1:1:1 ratio of RBC:FP:PLT
Dedicated porters for blood and coag testing
2 minute INR/aPTT spin time
Tranexamic acid incorporated (CRASH-2 trial)
No routine administration of cryoprecipitate
Factor VIIa
Termination?
Evaluation?
RED CELL AND VOLUME REPLACEMENT
• Correction of the deficit in blood volume with
crystalloid volume expanders will generally
maintain hemodynamic stability, while
transfusion of red cells is used to improve and
maintain tissue oxygenation
• Each unit of packed cells contains approximately
200 mL of red cells and, in an adult, will raise the
hematocrit by roughly 3 to 4 percentage points
unless there is continued bleeding.
Cont’
• At rest, oxygen delivery is normally four times
oxygen consumption, indicating the presence of
an enormous reserve.
• Thus, if intravascular volume is maintained
during bleeding and cardiovascular status is not
impaired, oxygen delivery will theoretically be
adequate until the hematocrit (packed cell
volume) falls below 10 percent.
• This is because adequate cardiac output plus
increased oxygen extraction can compensate for
the decrease in arterial oxygen content.
Cont’
• Oxygen release by transfused red cells is
diminished compared with normal red cells.
Storage reduces 2,3-bisphosphoglycerate (2,3BPG) levels, leading to a leftward shift of the
oxyhemoglobin dissociation curve.
• This abnormality, however, has not been shown to
be clinically important as the transfused red cells
regenerate 2,3-BPG to normal levels within six to
24 hours after transfusion.
Cont’
• These above considerations, however,
represent the optimal clinical response to
massive blood loss.
• An approach to the use of crystalloid and red
cell transfusions in adult patients suffering
from shock due to loss of circulating blood
volume secondary to hemorrhage is presented
separately
ALTERATIONS IN THE COAGULATION SYSTEM
• A patient being massively transfused may
present with preexisting coagulopathy because
of activation of coagulation secondary to tissue
trauma, prolonged hypoxia, hypothermia,
massive head injury, or muscle damage
DIC
• Such coagulopathy (eg, disseminated
intravascular coagulation) may be suspected in
these patients when there is microvascular
oozing, prolongation of the PT and aPTT in
excess of that expected by dilution, together
with significant thrombocytopenia, low
fibrinogen levels, and increased levels of Ddimer
Transfusion
• Even if coagulopathy does not exist and
coagulation parameters are normal before blood is
replaced, coagulation abnormalities may be
induced by the dilutional effects of blood
replacement on coagulation proteins and the
platelet count
• This occurs because packed red cell transfusions
are devoid of plasma and platelets, which are
removed immediately after collection.
Coagulopathy
• Some patients who suffer massive trauma may
present upon arrival at a trauma center with a
coagulopathy of trauma which is not due to DIC
or dilutional coagulopathy.
• This coagulopathy is caused by widespread tissue
injury/trauma and associated physiologic changes
(ie, acidosis, hypothermia, consumption of
coagulant proteins, and fibrinolysis) combined
with extensive blood loss and dilutional effects of
fluid replacement therapy
Effects of acidosis and hypothermia
• Both acidosis and hypothermia interfere with
the normal functioning of the coagulation
system
Acidosis
• Acidosis (ie, excess protons) specifically
interferes with the assembly of coagulation
factor complexes involving calcium and
negatively-charged phospholipids. As an
example, the activity of the factor
Xa/Va/prothrombinase complex is reduced by
50, 70, and 90 percent at a pH of 7.2, 7.0, and
6.8, respectively.
Hypothermia
• Hypothermia reduces the enzymatic activity of
plasma coagulation proteins, but has a greater
effect by preventing the activation of platelets
via traction on the glycoprotein Ib/IX/V
complex by von Willebrand factor. In tests of
shear-dependent platelet activation, this
pathway stops functioning in 50 percent of
individuals at 30º C, and is markedly
diminished in most of the rest.
Coagulation proteins
• The replacement of blood loss with red cells and a
crystalloid volume expander will result in gradual dilution
of plasma clotting proteins, leading to prolongation of the
prothrombin time (PT) and the activated partial
thromboplastin time (aPTT).
• In an adult, there will be an approximate 10 percent
decrease in the concentration of clotting proteins for each
500 mL of blood loss that is replaced.
• Additional bleeding based solely on dilution can occur
when the level of coagulation proteins falls to 25 percent of
normal.
• This usually requires 8 to 10 units of red cells in an adult.
Monitoring
• Thus, the PT, aPTT, and fibrinogen should be
monitored in patients receiving massive blood
transfusions of this magnitude.
• Two units of fresh frozen plasma (FFP) should be
given if the values exceed 1.5 times control.
• Each unit (in an adult) will increase the clotting
protein levels by 10 percent.
• Cryoprecipitate or, when available, virusinactivated fibrinogen concentrate, may be used
when fibrinogen levels are critically low (ie, <100
mg/dL)
Platelet count
• A similar dilutional effect on the platelet concentration
can be seen with massive transfusion
• In an adult, each 10 to 12 units of transfused red cells
can produce a 50 percent fall in the platelet count; thus,
significant thrombocytopenia can be seen after 10 to 20
units of blood, with platelet counts below
50,000/microL.
• For replacement therapy in this setting, six units of
whole blood derived platelets or one apheresis
concentrate should be given to an adult; each unit
should increase the platelet count by 5000 to
10,000/microL.
Monitoring recommendations
• In the massively transfused patient, assumptions
about possible dilutional effects should be
confirmed by measurement of the PT, aPTT, and
platelet count after the administration of every
five to seven units of red cells.
• Replacement therapy should not be based upon
any formula (eg, one unit of fresh frozen plasma
(FFP) for every four units of red cells), except
perhaps in patients with severe trauma
FFP, platelets, and red cells in trauma patients
• While replacement therapy with plasma,
platelets, and red cells should not generally be
based upon any set formula, results from a
number of observational studies suggest that
patients with severe trauma, massive blood
replacement, and coagulopathy have improved
survival when the ratio of transfused FFP
(units) to transfused platelets (units) to red
cells (units) approaches 1:1:1
COMPLICATIONS OF CITRATE INFUSION
• Large amounts of citrate are given with
massive blood transfusion, since blood is
anticoagulated with sodium citrate and citric
acid
• Metabolic alkalosis and a decline in the plasma
free calcium concentration are the two
potential complications of citrate infusion and
accumulation.
Metabolic alkalosis
• The pH of a unit of blood at the time of
collection is 7.10 when measured at 37ºC (7.6
at 1 to 6ºC) due to citric acid present in the
anticoagulant/preservative in the collection
bag.
• The pH then falls 0.1 pH unit/week due to the
production of lactic and pyruvic acids by the
red cells.
Acidosis
• Acidosis does not develop in a massively
bleeding patient even if "acidic" blood is
infused as long as tissue perfusion is restored
and maintained.
Metabolic alkalosis
• In this setting, the metabolism of each mmol of citrate
generates three meq of bicarbonate (for a total of 23
meq of bicarbonate in each unit of blood).
• As a result, metabolic alkalosis can occur if the renal
ischemia or underlying renal disease prevents the
excess bicarbonate from being excreted in the urine.
This may be accompanied by hypokalemia as
potassium moves into cells in exchange for hydrogen
ions that move out of the cells to minimize the degree
of extracellular alkalosis
Free hypocalcemia
• Citrate binding of ionized calcium can lead to
a clinically significant fall in the plasma free
calcium concentration.
• This change can lead to paresthesias and/or
cardiac arrhythmias in some patients
Recommendations for citrate infusion
• The maximum citrate infusion rate should be
0.02 mmol/kg per minute (since this represents
the maximum rate of citrate metabolism) and
the citrate concentration in whole blood is 15
mmol/L (0.015 mmol/mL).
Maximum citrate infusion rate
• Maximum citrate infusion rate (mmol/kg per
min)
= (mmol citrate per mL of blood x mL of
blood infused per min) ÷ wt (kg)
• mL of blood infused per
min = (0.02 ÷ 0.015) x wt
(kg) = 1.33 x wt (kg)
Maximum citrate infusion rate
• For a 50 kg recipient with normal hepatic
function and perfusion, the maximum rate of
blood transfusion to avoid citrate toxicity is
66.5 mL/min, which is equal to 8.9 units of
whole blood per hour (450 mL per unit) and
33.3 units of red cells per hour (approximately
120 mL per unit).
Hypocalcemia
• Thus, significant hypocalcemia should not
develop in this setting except under extreme
circumstances.
• However, the risk is substantially greater in a
patient with either preexisting liver disease or
ischemia-induced hepatic dysfunction.
• In such patients, the plasma ionized calcium
concentration should be monitored and calcium
replaced with either calcium chloride or calcium
gluconate if ionized hypocalcemia develops
Calcium Gluconate
• If 10 percent calcium gluconate is used, 10 to
20 mL should be given intravenously (into
another vein) for each 500 mL of blood
infused.
• If 10 percent calcium chloride is used, only
two to five mL per 500 mL of blood should be
given.
Cont’
• Calcium chloride may be preferable to calcium
gluconate in the presence of abnormal liver
function, since citrate metabolism is decreased,
resulting in slower release of ionized calcium
• Care must be taken to avoid administering too
much calcium and inducing hypercalcemia,
ideally by monitoring the ionized calcium
concentration
PREVENTION OF HYPOTHERMIA
• Rapid transfusion of multiple units of chilled
blood may reduce the core temperature
abruptly and can lead to cardiac arrhythmias
• Thus, during massive transfusion, a
commercial blood warmer should be used to
warm blood toward body temperature during
infusion.
PREVENTION OF HYPERKALEMIA
• Plasma potassium levels in stored blood increase
by approximately one meq/L per day due to
passive leakage of potassium out of red cells.
• This potassium is not actively transported back
into the red cells because membrane Na-KATPase activity is inhibited at 1 to 6ºC.
• The potassium concentration peaks at about 30
meq/L in whole blood and 90 meq/L in packed
red cells
potassium concentration
• The effect of blood transfusion on the plasma
potassium concentration can be appreciated
from a few simple calculations. Loss of one
unit (500 mL) of blood through bleeding
results in the loss of 1.5 meq of potassium
(five meq/L x 0.3 L of plasma); transfusion of
one unit of whole blood or red cells should
provide approximately 10 meq of potassium,
leading to a net gain of 8.5 meq.
Excess potassium
• Does not usually lead to a significant rise in the
plasma potassium concentration due to movement
into the cells, urinary excretion, and dilution
• Infants and patients with renal impairment may
develop hyperkalemia. In these patients, the
following steps can be used to minimize the risk
of hyperkalemia:
• Select only red cells collected less than five days
prior to transfusion.
• Any unit of red cells can be washed immediately
before infusion to remove extracellular potassium
SUMMARY AND RECOMMENDATIONS
• The management of the patient who is being
massively transfused requires careful and
ongoing consideration of a number of complex
physiological relationships.
• The primary concern is correction of ischemia
which can be accomplished at the outset by
aggressive volume expansion to maintain
perfusion pressure as blood is being readied
for infusion
Thank You