Transfusion talk for GIM 2013 - University of Colorado Denver
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Transcript Transfusion talk for GIM 2013 - University of Colorado Denver
•
Anemia, Oxygen Delivery
– Physiology
– Clinical evidence for RBCs
– Sepsis, CAD/ACS, Trauma
•
Coagulopathy
– Physiology
– Clinical evidence for FFP use
– Liver disease
•
Thrombocytopenia
– Evidence-based use of Platelets
– Uremia
Translate what you learn today to our trainees and
change the transfusion culture in Colorado
Help practitioners/educators:
Develop a framework for performing risk/benefit
analysis for each transfusion decision
To understand the clinical and physiologic
evidence behind those decisions
To challenge dogmatic transfusion practices
based on new evidence
Risk
Febrile transfusion reactions
Allergic reaction
Anaphylaxis
HIV
Hepatitis B
Terrible T’s
TRIM
TRALI
TACO
Incidence
<1 in 100
2-3 in 100
2 in 100,000
1 in 2,000,000
1 in 150,000
TRIM (transfusion-related immunomodulation)
Reduce rejection (kidney transplants 1960s)
Increased incidence of nosocomial bacterial infections
Marik; CCM, 2008
Transfusion
TRALI
Other
12%
Trauma
7%
Pneumonia
35%
Aspiration
11%
NonPulmonary
Sepsis
35%
-6
hours
0
13% of all transfused MICU patients
Mortality-8-9%
Differentiating TACO and TRALI
BNP
Hypertension vs. Hypotension
Leukopenia or fever (TRALI)
Diurese to low pulmonary venous pressures
Trial of diuresis Hypoperfusion TRALI
Trial of diuresis Resolution TACO
RBC (acquisition cost) ~$200 per unit
RBC (total cost) ~$1400-$2400 per unit
Higher if you factor in care for probable
complications
▪ TRALI (8% incidence in ICU)
▪ Nosocomial infection (10% increase per unit)
Transfusion
TRALI
Other
12%
Trauma
7%
Pneumonia
35%
Aspiration
11%
NonPulmonary
Sepsis
35%
-6
hours
0
Red Blood
Cell Transfusion
1) Physiologic
2) Hard outcome
3) Symptom?
Transfusion reactions
TRALI
TACO (hydrostatic edema)
TRIM (nosocomial infection)
Cost ($ and Human)
76YM w/ HTN, CAD (Hx MI) admitted to the ICU with
pneumonia severe sepsis
Quickly improved with IVF (5L), oxygen, antibiotics
overnight- transferred to floor
BP- 110/50 (140/90), HR 110, Temp-100.8
SPO2 90% on 4LNCO2
Lactate-4.8 2.8, Hgb 9.67.6, Creatinine 1.81.4 (0.8)
BP- 110/50 (140/90)
HR 110, Temp-100.8
1) Physiologic
SPO2 90% on 4LNCO2
2) Hard outcome
3) Symptom?
Lactate-4.8 2.8
Creatinine- 1.81.4 (0.8)
Transfusion reactions
TRALI
TACO (hydrostatic edema)
TRIM (post-transfusion
infection)
Cost ($ and Human)
Hgb 9.27.6
Physiologic benefit RBCs
SPO2 x Hgb x CO (SV x HR)
Hgb=3.5
Heart rate (beats/min) = 116 - 4.0 x Hgb (g/dL)
Zimmerman; Critical Care Med, 2004
1st case- Epi Q’s re: anemia and transfusion
Need hospital transfusion numbers
2nd case: Sepsis: APACHE II<20, 52YM,
increase O2 delivery?, Improve outcome
benefit? When?
Harm?
Leukoreduction?
3rd case: Post-op knee 55YM: AF w/ RVR,
known CAD, improve myocardial O2 delivery?
rehab potential? ADLs?
4th case: NSTEMI (HCT 25), AF w/ RVR, No
EKG changes, transitions to STEMI
Age of blood?
Everything else is extrapolation from these studies
Do summary slide here of key points (with pictures)
Incidence: X% at 3 days
Mechanisms (non-bleeding)
Loss (phlebotomy)
▪ Sepsis; X% total hgb drop
Suppression (TNF, IL-1, IL-6)
▪ ↓ Epo + Epo receptor
▪ Induce apoptosis of erythroblasts
▪ Decreased availability of Iron
Destruction-RES system
Dilution
Epidemiology of Transfusion in the
Critically Ill
Napolitano; Critical Care, 2004
PROPENSITY MATCHED
30 DAY MORTALITY
Adj 30d Mort: 1.65, p< 0.001
ABC Study Outcomes (Europe)
Difference in Mortality by Number of Units Transfused.
Vincent, J. L. et al. JAMA 2002;288:1499-1507
Copyright restrictions may apply.
ABC Study Outcomes
Survival Analysis by Transfusion Status Among Propensity-Matched Patients.
28-day mortality
23% vs. 17%, p=0.05
Vincent, J. L. et al. JAMA 2002;288:1499-1507
Copyright restrictions may apply.
Transfusion
TRALI
Other
12%
Trauma
7%
Pneumonia
35%
Aspiration
11%
NonPulmonary
Sepsis
35%
-6
hours
0
Multicenter RCT, Canada, n=838
Hgb 7 vs. 10
Who: non-bleeding, CAD (600 ex)
Ischemic heart disease (n=257)
Outcomes
30d Mortality 18% vs. 23%, p=.10
Hospital Mort 22% vs. 28%,p=.05
Subgroups
APACHE II < 20
(9% vs 16%, p=.03)
Age < 55
(5.7% vs. 13%, p=.02)
Hebert; NEJM, 1999
Complications
▪ ARDS or pulmonary edema
(8% vs. 14%, p<.01)
▪ MI (0.7% vs 2.9%), p=.02
Multicenter RCT, US/Canada, n=2016
Hgb 7 vs. 10
Who: age> 50, Hip repair
Clinical evidence/RF Heart disease
Hgb <10 w/in 3d surgery
Outcomes
60d mort/10 ft: 35% vs. 35%, p=.90
MI/UA/Death: No difference
Discharge Location
Functional outcomes (Fatigue, ADL)
Notes
2 units. vs. 0 units
1.3 g/dL difference nadir hgb
Carson, NEJM, 2012
Complications
▪ No differences in 20+
transfusion outcomes
DO2 = CO x (SPO2 x hgb)
Oxygen kinetics?
Will ↑RBCs ↑O2 utilization
Assumptions: transfused RBCs
▪ Don’t alter the flow (CO)
▪ No alteration inO2 kinetics
↑DO2 ≠ ↑VO2
1) delivery dependent hypoxia
2) microvascular delivery
3) 0xygen kinetics maintained
Transfused RBCs :
Greedy
Flow, O2 kinetics
Fragile
Autoregulation, plugging
Sticky
adhesionshunting
microvesicles
16 pt- Septic Shock and hgb <10g/dl
1) Dobutamine 10mcg 800cc RBCs (3 units)
2) 800cc RBCs (3 units) Dobutamine 10mcg
DO2 (jncreases in both scenarios)
Dobutamine 48.5 (± 6.9)
PRBCs 21.3 (± 4.3)
VO2 increased only with Dobutamine
21.7 (Dobutamine) vs. 2.2 (PRBCs)
Conclusion: In septic patients with delivery (DO2) dependent
decreases in VO2, RBC transfusion does not improve VO2.
Lorente; Critical Care Med, 1993
Zimmerman; Critical Care Med, 2004
The storage lesion (average US age=17 days)
↓deformability, ↑ fragility
Loss of antioxidantsHgbMethemoglobin
Lose 2,3 DPG (7-14 days), ATP, NO
WBC may accelerate storage lesion
▪ ↑ IL-1, IL-8, TNF, bioactive lipids, HLA-ag
Epidemiology (all RBCs>14d)
↑ PNA, infxn, MOF, LOS in TRAUMA
↑ Morbidity/Mortality in Cardiac Surgery
▪ 2 RCTs ongoing (10/14d vs. 21)
Interventional Studies (MICU)
Physiologic outcomes with inconsistent results
ABLE (Age of Blood Evaluation) ICU Patients
▪ n=2510, 25 centers Canadian, double blind RCT
▪ Vent >48 hours, ICU, request for 1 RBC unit
▪ Fresh (<7d) vs. standard (15-20d)
▪ 90day mortality (power 25%20%)
Epidemiology
▪ Association with TRALI, infection, mortality
Universal leukoreduction- 2005 in US
No outcome benefit before and after studies
No benefit in recent RCTs (Trauma/Med/Surg)
Mortality, Infection, TRALI
Except CABG less post-op infection
Should we switch back to non-leukoreduced
blood?
more economical
CAD/ACS
Myocardium oxygen extraction ratio- 55-70%
CAD or ACS flow limited
Do RBCs increase DO2 myocardial VO2?
Transfused RBCs
NO sink, ↓ ATP, reduce microvascular flow
Hypercoaguable, ↑platelet aggregation
↓worsening oxygen kinetics
24,112 patients from 3 ACS (NSTEMI) trials
10% (2401) transfused
Adjusted for 50+ co-morbidities and time from
admission
Grouped by nadir HCT; 20-25%, 25-30%, >30%
Adj. probability of death at 30d w/transfusion
Rao; JAMA, 2004
39, 922 pts, ACS (NSTEMI and STEMI)
STEMI- Improved outcomes when transfused
up to Hgb≥ 12 g/dL
NSTEMI- Worse outcomes when transfused
at any Hgb level!!
Registry: ACS patients: Worse CV outcome
and death with transfusion down to hgb < 9
g/dL (equivalent below 9 g/dL)
Sabatine; Circulation, 2005
Singla; Am J Card, 2007
TRICC-(357 -CV disease), (257-IHD)
Hgb-7 vs 10 g/dL
No difference in 30 day mortality (0.3%)
FOCUS- 2016 CAD or RF for CAD, Age>50
Hgb-7 vs 10 g/dL
No difference in mortality or functional
outcomes
STEMI Up to Hct 30% if active ischemia?
NSTEMI Up to Hct 20-25% if active ischemia??
CAD (no active ischemia) hgb 7mg/dL (FOCUS)
Alternatives to increase supply and reduce demand
Reverse or avoid inadequate
tissue oxygenation due to
inadequate delivery
Transfusion reactions
TRALI
TACO (hydrostatic edema)
TRIM (nosocomial infection)
Cost ($ and Human)
Risk
Febrile transfusion reactions
Allergic reaction
Anaphylaxis
HIV
Hepatitis B
Terrible T’s
TRIM
TRALI
TACO
Incidence
<1 in 100
2-3 in 100
2 in 100,000
1 in 2,000,000
1 in 150,000
TRIM (transfusion-related immunomodulation)
Reduce rejection (kidney transplants 1960s)
Increased incidence of nosocomial bacterial infections
Marik; CCM, 2008
Within 6 hours
ALI Dx criteria
1) Acute
2) Bilateral infiltrates
3) Hypoxemia
4) Not hydrostatic
edema (TACO)
Associated most commonly with platelets and plasma
Mortality 30-50% in ICU patients
Antibody mediated (Anti-HLA I or II, Anti-neutrophil)
Non immune mediated
Common-5-8% MICU pts transfused (29% bleeding liver disease)
Massive transfusion studies
No analysis of FFP
Recent ALI association studies have identified FFP as an
independent risk factor (9 studies)
Ruptured AAA repair(1) , MICU (3), trauma (2) mechanically ventilated
(2), Sepsis (1)
No association of RBCs and ALI when adjust for FFP
FFP/Plts most common causative agents TRALI in critically ill
MICU TRALI incidence:
5-8% transfused pts
Mortality- 41-53%
Benson, ICM, 2010
Vlaar, CCM, 2010
Gajic O, TRALI in the
Critically ill, AJRCCM
2007
Benson, ICM, 2010
Silliman C,
Blood 2003
Wallis JP,
Transfusion 2003
13% of all transfused MICU patients
Mortality-8-9%
Differentiating TACO and TRALI
BNP
Hypertension vs. Hypotension
Leukopenia or fever (TRALI)
Diurese to low pulmonary venous pressures
Trial of diuresis Hypoperfusion TRALI
Trial of diuresis Resolution TACO
RBC (acquisition cost) ~$200 per unit
RBC (total cost) ~$1400-$2400 per unit
Higher if factor in care for probable complications
▪ TRALI (8% incidence in ICU)
▪ Nosocomial infection (10% increase per unit)
Reverse or Avoid
inadequate tissue
oxygenation due to
inadequate delivery
Transfusion reactions
TRALI
TACO (hydrostatic edema)
Infection (TRIM)
Cost ($ and Human)
Special Populations:
CAD/ACS
Sepsis
Trauma
All blood products associated with morbidity and
mortality in dose-dependent manner
TRALI
Infection
MOF
Ratio debate: FFP:PRBC:Plts
Bleeding control?
Coagulopathy?
TRICC approach (hgb=7) safe and effective postresuscitation
Most hospital have a protocol
RBCs:FFP~2:1
General measures:
Ionized Calcium > 0.9 mmol/L
pH >7.10
Temperature > 34 degrees
Plug hole in vessel!!
Pressure on hole (allow time for clotting)
Change pressure gradient in vessel
▪ Embolization, lower driving pressure (hypotensive
resuscitation)
1.0
1.5
2.0
Reduce Bleeding
Transfusion
complications
3.0
1) Thoracentesis and elevated INR
(Coumadin)? LP?
Go over pre-procedure prophylaxis data
2) Liver disease paracentesis
GI bleed (elevated INR)
Dose (use of vit K), what if bleeding
3) Really (18) High INR on Coumadin
Head bleed, Factor VIIa?
5) Uremia procedure- what to do?
6) PNA, malignancy- Plts 20k
1.5
3.0
Prevent Bleeding?
Stop Bleeding?
Transfusion
complications
Gajic; Critical Care Med, 2006
If Bleeding and Coagulopathy
2010 AABB guidelines: consider FFP for:
Yes:
▪ Massive transfusion < 1:3 ratio (moderate/low grade)
▪ Coumadin induced ICH (very low grade)
Neutral
▪ Surgery/Trauma (no massive transfusion) (very low)
NO
▪ Coumadin high INR No ICH (very low)
▪ All non-bleeding situations (silent on liver disease)
Central lines
Arterial Lines
Thoracentesis
Liver disease
Paracentesis
Percutaneous/Transjugular liver biopsy
Prior to banding for nonbleeding varices
Dental extraction (use DDAVP)
The INR=1.5 story
Prothrombin time > 1.5 x upper limit normal:
▪ safe to perform surgery with normal hemostasis
ISI developed to standardize tissue factor
ISI in most labs was 1
1:1 relationship btw PT > 1.5 x ULM and INR=1.5
Now back calculation yield an INR-1.8-2.2
▪ normal hemostasis
Transfusing Platelets
44% of ICU patients thrombocytopenia
Transfusion Triggers:
No bleeding RF: <10k; bleeding RF???: <20k
Large vessel Bleeding: 50k -60k
Diffuse microvascular bleeding: 100k
Pre-procedural prophylaxis: 50k; Surgical
prophylaxis: 100k
Measure plts 1 hour after to evaluate for
consumption/destruction
Main risk TRALI (highest of all blood products)
Mechanism:
Altered GP1B, ↓IIb/IIIa receptors (adhesion/aggregation)
Dysfunctional vWF, Less functional factor VIII
Plts↑ PGI2 levels, ↓plt TxA2, ADP
Effects uremic toxins/anemia
Treatment: (BUN does not correlate)
Dialysis
**Desmopressin (48h) , *Cryoprecipitate (1 h onset)
EPO/Transfuse to HCT=30
Estrogen (0.6mg/kg IV QD x 5d)
134 trauma patients randomized to Novo
VIIa after 6 units of blood in 4 hours
ARDS 16% vs. 4%, p= .03
Boffard KD, J Trauma 2005