Transcript Avoiding Allogeneic Transfusion: A Case Study

Comprehensive Patient
Blood Management
Avoiding Allogeneic Transfusion:
A Case Study in Patient Blood Management
Irwin Gross, M.D.
May, 2012
Disclosures
Irwin Gross, MD
• Medical Advisory Board, Strategic Healthcare Group
Learning Objectives
• Name the three pillars of patient blood management
• Name three adverse outcomes associated with transfusion
• List four tools that can be used in patient blood management
to limit the risk of transfusion
• Describe the role of parenteral iron in treating anemia
• Name two types of perioperative autologous blood collection
• List two relative contraindications to cell salvage
What is Patient Blood Management:
The Three Pillars
Optimize
erythropoieis
Minimize
bleeding &
blood loss
© Axel Hofmann/Shannon Farmer –
SHEF Meeting Perth August 2010
Harness &
optimize
physiologic
tolerance of
anemia
Anemia independently associated with increased:
• morbidity 5-75% incidence in
patients presenting
• hospital length
of stay
for elective surgery
• likelihood of transfusion
Shander 2004
Anemia
• mortality
Spahn DR. Anesthesiology 2010; 113(2) 1-14
Beattie WS, et al Anesthesiology 2009; 110(3) 574-81
Dunne JR, et al J Surg Res 2002; 102: 237-44
Shander A. Am J Med 2004; 116(7A) 58S-69S
Bleeding associated with increased
• Morbidity
• ICU and hospital length of stay
• Mortality Procedural
• Elective surgery ~0.1%
bood loss & Bleeding
• Subgroups:
• Vascularbleeding
5–8%
• Up to 20% with severe bleeding
• Major organ damage 30–40%
Causes
• On average 75 – 90% local surgical interruption or
vessel interruption
• 10–25% acquired or congenital coagulopathy
Shander A. Surgery 2007
RBC transfusion independently associated
in a dose-dependent relationship with
increased:
•Morbidity
•ICU and hospital length of
stay
•Mortality
Transfusion
Beattie WA, et al Anesthesiology 2009
Murphy GJ, et al Circulation 2007
Salim A, et al J Am Coll Surg 2008
Bernard AC, et al J Am Coll Surg 2008
Hearnshaw SA, et al Aliment Pharmacol Ther 2010
Blair SD, et al Br J Surg 1986
Impact of Transfusion on Patient Outcomes
Author (year)
Koch et al (2005)
Murphy et al (2007)
Surgenor et al (2009)
Pedersen et al (2009)
Nikolsky et al (2009)
van Straten et al (2010)
D’Ayala et al (2010)
O’Keeffe et al (2010)
Veenith et al (2010)
Population
Cardiac surgery
n
Impact of Blood Transfusion
11,963 - Higher postop mortality rate
- Higher postop morbidity rate (RF, prolonged
ventilatory support, serious infection, cardiac
complications, & neurologic events)
Cardiac surgery
8,598 - Higher mortality rate
- More ischemic complications
- More infectious complications
Cardiac surgery
3,254 - Decreased survival after cardiac surgery
Total hip
4,508 - Higher mortality rate
replacement
- More pneumonia
PCI after MI
2,060 - Higher 30-day and 1-year mortality rate
Cardiac surgery
10,435 - Worse early survival
Lower extremity
300
- More postop adverse events
amputation
- Longer ICU/hospital stay
Lower extremity
8,799 - Higher mortality rate
revascularization
- More pulmonary complications
- More infectious complications
Elderly undergoing 874
- Higher mortality rate
cardiac surgery
- Longer ICU/hospital stay
Physiologic Impact of Red Cell Transfusion
Author
(year)
Population
Babineau et Postoperative
al (1992)
Silverman et Septic shock 21–88 yrs
al (1992)
Marik et al Septic adults
(1993)
Lorente et al Septic adults
(1993)
Gramm et al Septic shock 46 ± 3 yrs
(1996)
Casutt et al Postoperative 32–81 yrs
(1999)
Fernandes et Septic shock 18–80 yrs
al (2001)
Walsh et al Euvolemic anemic critically ill
(2004)
patients
Suttner et al Volume-res mechanically
(2004)
ventilated patients
Mazza et al SIRS/Sepsis
(2005)
n
Blood
Transfused
↑Hb
↑DO2
↑VO2 ↓Lactate
31
328 ± 9 mL
Yes
Yes
No
No
21
2 units
Yes
Yes
No
No
23
3 units
Yes
Yes
No
No
16
2 units
Yes
Yes
No
?
19
2 units
Yes
No
No
?
67
368 ± 10 mL
Yes
Yes
No
?
10
1 units
Yes
No
No
No
22
2 units
Yes
?
?
No
51
1 or 2 units vs.
100% FIO2
1–3 units
Yes
Yes
No
?
Yes
?
?
No
29
What are “Transfusion Alternatives”?
•
•
•
•
•
Optimize hemodynamics and oxygenation
Physiologic tolerance of anemia
Use of erythropoietic stimulating agents
Use of intravenous iron
Minimizing blood loss
– Manage coagulopathy
– Anti-fibrinolytics
– Perioperative cell collection and reinfusion
Our Patient
• A 68 year old retired immunology professor
requires revision of a prior right hip
arthroplasty due to aseptic loosening with
severe instability and functional limitation
• Past medical history is significant for
rheumatoid arthritis and Type 1 vWD
• Patient underwent a recent hemicolectomy
for T1N0M0 (Stage 1) colon cancer at
another hospital without a blood
management program
Our Patient
• The patient is referred to an
orthopedic surgeon
• A total hip arthroplasty is planned
• The patient, having read the article
summarized on the next slide, requests
that transfusion of allogeneic blood be
avoided unless surgical bleeding is life
threatening
Influence of Transfusion on Colorectal
Cancer Recurrence
• Cochrane meta-analysis involving
12,127 patients
• Evaluated role of transfusion in
colorectal cancer recurrence
• Overall OR for recurrence was 1.41
(95% CI 1.20-1.67) in transfused
patients
Amato, A, et al. Cochrane Database System Rev
2006;(1): CD005033
Reasons to Avoid Transfusion
• Transfusion is associated with:
–
–
–
–
Increased perioperative infections
Increased length of stay
Increased short term mortality
Transfusion reactions, some life
threatening
– Increased incidence of cancer
recurrence and decreased disease-free
and long term survival
Pre-operative Screening for Anemia
• The patient should be screened for
anemia -he is undergoing surgery with
significant blood loss
– CBC
– If CBC shows anemia (< 13 g/dL) then
additional lab tests required
• Iron, iron binding capacity, ferritin, Vitamin
B12, creatinine, reticulocyte count
• Folate if MCV > 100 fl
Scheduling
• The ideal window to evaluate a patient for
pre-operative anemia is 21-30 days before
surgery
– Medicare will not pay for lab studies > 30 days
• If commercial insurance or known history of anemia
or co-morbidity associated with anemia, screen
sooner (more time to treat anemia is better)
– Treatment of chronic anemia with iron, EPO or
both requires (at least) 3-4 weeks
– The clinical condition may require the case to be
scheduled sooner (unstable cardiac disease;
cancer diagnosis)
Scheduling
• If procedure is truly elective, and
anemia cannot be managed in the
available time, surgery should be
deferred
• Occasional patients will need referral to
specialist: hematologist,
gastroenterologist, etc.
Our Patient
• Surgery is scheduled to take place in 24 days. Lab
results are as follows:
–
–
–
–
–
–
Iron:
Total iron binding:
% Saturation:
Ferritin
Hemoglobin
Reticulocyte count
20 ug/dL (28-170)
250 ug/dL (261-478)
8%
(15-45)
600 ng/mL (45-500)
10.1 g/dL (14-17)
25 Th/uL (22-98)
Our Patient
• Diagnoses
– Iron deficiency anemia (blood loss from
recent chronic lower GI blood loss and colon
surgery treated with enteral iron sulfate)
• Enteric iron is ineffective when there is
inflammation, e.g. rheumatoid arthritis
– Anemia of Inflammation (functional iron
deficiency – patient has rheumatoid arthritis)
• Recommended Rx
– Intravenous iron
– Consider erythropoietin
Anemia Management: Intravenous Iron / EPO
• “Standard” regimen for perioperative anemia;
hemoglobin between 10-13 g/dL; non-vascular,
non-cardiac surgery
– 40,000 units of erythropoietin on days 21, 14,
and 7 pre-op, and on day of surgery
• Patient must have transferrin saturation > 20%
and ferritin > 100 ng/ml to be reimbursed by
Medicare
– 200 mg I.V. iron sucrose with each EPO dose
– 1 mg folate, p.o., daily
– 500 mg Vitamin C, twice daily
Should We Use EPO and Iron or Iron Alone?
• Reasons to use EPO:
– Patient has only 24 days till surgery with Hgb of 10.1
g/dl
– EPO improves rate of response to iron
– Rheumatoid arthritis may result in decreased
endogenous EPO production
• Reasons not to use EPO
– Increased VTE risk
– Some data suggests shortened survival and time to
recurrence in some malignancies with EPO
– But, transfusion is associated with shortened survival
and time to recurrence in malignancy and increased
perisurgical mortality
JAMA. 2008;299 (8): 914-924
Anesthesiology. 2009 Mar; 1 10(3):547-81
Our Patient
• After discussion of the risks and
benefits of EPO (informed consent),
the patient consents to the use of
EPO
– Orders are written for three doses
of EPO between now and surgery, by
subcutaneous injection (600
units/kg)
– A fourth dose of EPO will be given on
post-op day one if hemoglobin is less
than 8.0 g/dL
– Goal: lowest dose to avoid
transfusion
Iron Administration
• Intravenous iron should always be given
during a course of treatment with EPO unless
iron saturation is > 35% or ferritin > 1,000
ng/ml
• Three “classes” of IV iron available in U.S.
–
–
–
–
Minimal cross reactivity re: reactions
Iron sucrose and iron gluconate
Ferumoxytol (paramagnetic nanoparticle)
Iron dextrans
• Fewer ADE’s with low molecular weight iron
dextran than high molecular weight iron dextran)
David H et al Oncologist 12:231-242, 2007
J Am Soc Nephrol 18: 975-984, 2007
Iron Sucrose vs. Iron Dextran vs. Ferumoxytol
• Iron sucrose
– Most appropriate for serial encounters or
total dose of 300 mg or less
– Comes in 100 mg vials
– Maximum dose we use is 300 mg in 100 ml
saline over 60 minutes
– Lowest rate of serious adverse drug reactions
– Characteristics and use of iron gluconate are
similar
Iron Sucrose vs. Iron Dextran vs. Ferumoxytol
• Low molecular weight iron dextran
– Best option for total dose iron replacement
(TDI)
– Use when single encounter and iron required
exceeds 300 - 500 mg
– Requires administration of test dose
– Remaining dose given over 1 – 2.5 hours, up
to 1,500 mg
– Low incidence of A.D.E.’s (3.3 / million doses)
– I recommend against high molecular weight
iron dextran
Iron Sucrose vs. Iron Dextran vs. Ferumoxytol
• Ferumoxytol
– Can administer 510 mg of iron in 17
seconds (30 mg/sec)
– No test dose required
– Least experience, but seems to have a
good safety profile
– Higher drug cost than other options
What about Enteric Iron?
Hepcidin, Inflammation and Iron Metabolism
J Am Soc Nephrol
18: 394-400, 2007
Contraindications to Iron
• Theoretical concern in infection /
sepsis – some bacteria use iron as a
growth factor
• But remember, transfused blood
provides iron in the form of heme
• Immunomodulation increases risk
of infection
S. aureus and Iron-regulated Surface Determinant
(IsdB) .
Lowy FD. N Engl J Med 2011;364:1987-1990.
Our Patient
• With each EPO dose, we decide to
give our patient 200 mg of I.V. iron
sucrose (600 mg total)
• Additional iron will be given post-op
based on post-op hemoglobin
– Approximately 500 mg iron required
to replace depleted stores
– Need additional 150 mg for each
g/dL decrease in hemoglobin below
13 g/dL
Our Patient
• On the day of admission, our
patient has a hemoglobin of
12.8 g/dL and an elevated
reticulocyte count
• The patient signs informed
consent for transfusion only if
needed to prevent death from
severe hemorrhage
Intraoperative Management – Day of Surgery
• Acute normovolemic hemodilution
(ANH)
• Intraoperative autologous blood
collection and re-adminstration
(“cell salvage”)
• DDAVP
• Anti-fibrinolytics (e.g. tranexamic
acid
• Meticulous surgical hemostasis
Acute Normovolemic Hemodilution
• Conservation of red cell mass by
decreasing hematocrit of shed blood
• Fresh whole blood, with intact
platelets and clotting factors, available
at end of case for transfusion
• Studies show reduced blood loss in
joint arthroplasty, spine surgery,
cardiac, hepatic resection, major colon
operations, and radical cystectomy
Acute Normovolemic Hemodilution – How Is It Done
• Replace volume with crystalloid or
colloid
– We generally use HES (tetrastarch)
• Usually requires 10 minutes / unit
• Proper labeling
• Blood typically remains at room
temperature in O.R. prior to reinfusion
• Generally re-administered in reverse
order of collection
– most hemodiluted given first
– unit with most clotting factors last
Our Patient
• We anticipate the possibility of 2
liters of blood loss
– Based on the professor’s body
weight and hemoglobin, up to four
units might be collected before
surgery; we collect two
– Replaced with 1,000 ml of
hydroxyethyl starch
• We use tetrastarch
– His hemoglobin at the start of the
procedure would be 10.0 g/dL
Intraoperative Cell Salvage
• Indicated when significant blood loss is
anticipated (may be as little as 250 ml in
a small patient with anemia)
• Full set-up when significant blood loss is
likely
• Collection only set-up when significant
blood loss is possible
• Salvage efficiency is technique
dependent
– Low suction pressure
– Eliminate skimming
– Wash sponges
Intraoperative Cell Salvage
• Relative contraindications
– Bacterial contamination
– Some foreign material (antibiotics, topical
hemostatic agents, methyl methacrylate)
– Malignancy
• Most contraindications can be addressed
through a combination of increased wash
volume and filtration
– Two suctions, one for waste
– Leukocyte reduction filter for bacteria and
tumor cells
– Irradiation for tumor?
Blood Salvage and Cancer Surgery:
Meta-analysis
Conclusion:
IBS is not inferior to
traditional intraoperative
allogeneic transfusion with
regard to increased cancer
recurrence or development
of metastasis
Waters et al, Transfusion doi: 10.1111/j.1537-2995.2011.03555.x
Our Patient
• We decide to set up the Cell Saver in
anticipation of significant blood loss.
• If the patient was having surgery for
tumor, a leukocyte reduction filter
would be used
• Waste suction will be used to clear
field if topical hemostatic agents
used
Pharmacologic Agents to Limit Blood Loss
• Desmopressin (DDAVP,
Stimate)
– Releases von Willebrand’s
factor from endothelial
cells and increases factor
VIII levels
– 0.3 mcg/kg in 50 mL over
15-30 minutes
– Can be repeated several
times
– Minimal evidence of
efficacy in reducing surgical
blood loss except in vWD
Pharmacologic Agents to Limit Blood Loss
• Antifibrinolytic agents
– Amicar
– Tranexamic Acid
• Inhibits clot lysis
• 10-30 mg/kg loading dose,
followed by 1-2 mg/kg/hr
• Decrease dose for renal
insufficiency
• Good evidence base: 30%
reduction in blood loss in
major orthopedic cases
including multilevel spine and
TJA
Br J Anaesth 2004; 93:842-58
Pharmacologic and Other Agents to Limit
Blood Loss
• Topical hemostatic agents
– Fibrin glue (thrombin and
fibrinogen concentrate)
– Mechanical hemostatic agents
(collagen, cellulose, gelatins, etc.)
– Active hemostatic agents
• Bovine or human thrombin
• Gelatin plus thrombin
• Synthetic glues
• Saline-cooled radiofrequency
“cautery”
Our Patient
• Surgeon plans to use topical hemostatic
agents as needed
• This patient has a history of mild type 1
vWD
– Plan to administer 30 mcg of DDAVP 15
minutes before surgery
• Will administer 20 mg/kg of tranexamic
acid just before the start of surgery and
begin an infusion of 2 mg/kg/hr
– Will discontinue infusion when surgery is
completed
• Some surgeons use TXA topically
Day of Surgery
• Both the femoral and
acetabular component
require revision
• Unexpected surgical
bleeding is
encountered
Intraoperative Course
• Four cell “salvage” runs return a
total of 1,075 ml of processed
blood with an average hematocrit
of 55% (equivalent to about 3 units
from the blood bank)
• The two ANH units are returned
toward the end of surgery
Post-op Day One
• The patient’s post-op hemoglobin is
7.9 g/dL and our patient has been
extubated
• He is hemodynamically stable
• As planned, a fourth dose of
erythropoietin is administered
• The surgeon initiates the “minimum
blood volume” phlebotomy protocol
to minimize blood lost for diagnostic
testing
Strategies for Reducing Phlebotomy Blood
Loss
• Eliminate “extra tubes”
• Eliminate under and over draws
• Individual nurse and phlebotomist
education
• Selection of testing equipment
with low requisite sample volume
• Increased point-of-care testing
• Reduce unnecessary testing
• Reduced tube size
• Selective use of microtainers
Highly Conservative Phlebotomy
• Using a highly conservative
protocol, median phlebotomyassociated blood loss (PBL) in
the ICU was reduced 80% (40 ml
vs. 8 ml)
• Mean drop in hemoglobin in ICU
decreased from 2 gm/dl to 1.2
gm/dl
Harber CR. Anesthesia and Intensive Care 34:4, 2006
If on post-op day one…
•
•
•
•
Our patient’s hemoglobin is 6.7 g/dL
His reticulocyte percentage is 7.8%
His iron saturation is 13%
He is walking 15 feet with assistance, but
becomes short of breath and feels tired
What would you do?
Post-op Iron Therapy
• Post-op inflammatory response
creates functional iron deficiency
due to increased hepcidin (our
patient also has RA)
– Labs show decreased transferrin
saturation (% saturation) below
20%
• Oral iron salts (e.g. ferrous
sulfate) are poorly absorbed and
prolong post-op ileus
Our Patient
• We decide to administer 900 mg of
low molecular weight iron dextran
based on the patient’s IBW of 70 kg
and hemoglobin deficit of 6 g/dL
• Daily folate, 1 mg for one month
• Daily Vitamin C for one month
• Patient is discharged home on postop day 2 with a hemoglobin of 8.1
g/dL
• One month after surgery, the
patient is recovering nicely with a
hemoglobin is 11.9 g/dL
Patient Blood Management:
The Three Pillars
Optimize
• Pre-op anemia
screening
erythro• ESAs
poieis
• Intravenous
Iron
• ANH
• Cell Salvage
• DDAVP
• Minimize
TXA
•bleeding
Topical
&
hemostatics
loss
• blood
Meticulous
surgical
hemostasis
• Minimize
phlebotomy
© Axel Hofmann/Shannon Farmer –
SHEF Meeting Perth August 2010
Harness &
• Optimize
optimize
hemodynamics
•physiologic
Optimize
oxygenation
tolerance
of
• Low hemoglobin
threshold
for
anemia
transfusion