Targeted Transfusion in Cardiac Surgery
NATHAEN WEITZEL MD A SSO CIATE PR O FE SSO R O F A NE ST HE SIOLOGY UNIVE RSITY O F CO LO R ADO SO M DENVER CO
Disclosures
• Nothing relevant to this subject
Roadmap:
• Outline the risks of anemia in cardiac surgical patients.
• Discuss whether transfusion changes the risk profile and improves the outcome of the anemic patient.
• Consider when and why to transfuse in cardiac surgical patients.
Anemia – What is the risk?
Anemia:
• World Health Organization defines as < 13 g / dL (men) / 12 g / dL (women).
• More than 50% of cardiac surgical patients are in this range.
• Anemia has long been associated with decreased outcomes with multiple observational trials demonstrating this.
Loor, G., et al.,The Journal of thoracic and cardiovascular surgery, 2012. 144(3):538-546. Bennett-Guerrero, E., et al.. JAMA, 2010. 304(14): p. 1568-75. Snyder-Ramos, S.A., et al., Transfusion, 2008. 48(7): p. 1284-99.
Known Risks:
The Journal of thoracic and cardiovascular surgery 2012;144:538-46
• Increased mortality • Increased ICU stay • Increased transfusion rates • Prolonged ventilation • Renal insufficiency • Stroke • Delirium
• 3003 patients identified for cardiac surgery who did not receive any blood products
• Univariate and multiple logistic regression analysis
Conclusions: Preoperative HCT and lowest HCT during CPB Independently associated with major
morbidity including respiratory failure, renal insufficiency, stroke and reoperation
Not independently associated with mortality Combined pre-op HCT <40 and CPB nadir HCT
<28 associate with highest morbidity rates.
So a low Hct is bad – just transfuse……
Transfusion Threshold
Koch CG, et,al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Ann Thorac Surg 2006;81:1650-7.
Koch, CG et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006;34:1608-16.
Mortality, Renal, Respiratory, Infection,
Cardiac, Neurologic
More Transfusion Studies: CPB
• Koch -2006 Ann Thoracic Surgery
• 7000 pts
• Worse functional status with tx
• Surgenor – 2006 Circulation
• 8000 pts. RBC and Anemia associated with 27% increase in risk of heart failure
• Murphy 2007 Circulation
• 8000 pts
• Propensity matched retrospective cohort study looking at both infectious outcomes and ischemic outcomes associated with transfusion
Decreased Functional status, More Heart
Failure, More infectious / ischemic
outcomes.
• 17 center, prospective randomized trial
• 2007 patients randomized
• Those with post-op (heart surgery) Hg < 9.0 randomized to liberal vs restrictive protocol
• Transfused at either 9.0 vs 7.5
All Cause Mortality at 90 days was
significant with OR 1.64 and p = 0.045. In
Favor of Liberal group!!!
• Cleveland Clinic – retrospective review spanning more than 90000 cardiac surgeries since 1983.
• Identified 322 Jehovah’s Witness patients with complete data
• Propensity matching carried out as well as unadjusted results.
Outcomes measured included: • Return to the operating room for bleeding • Renal failure, stroke • Atrial fibrillation, myocardial infarction • Sepsis, respiratory insufficiency • In-hospital death.
Witnesses had lower occurrence: • postoperative myocardial infarction, • prolonged ventilation, • additional operation for bleeding; • shorter intensive care unit and postoperative
lengths of stay
Survival: 5 yr 10 yr 15 yr 20 yr
Witness (%) 86 69 51 34
Non-Witness (%)
74 53 35 23
Nadir HCT: Summary of trials Observational and Randomized data for > 20K patients: • Nadir HCT ranging from 20-24% found
to be inflection point • Found to be associated with increased
mortality, stroke, AKI, prolonged ventilation, reoperation, infection
Loor et al. The Journal of thoracic and cardiovascular surgery 2012;144:538-46.
Loor et al. The Journal of thoracic and cardiovascular surgery 2012;144:538-46.
Conclusions …..
• Identified that Anemia is bad for you
• Identified that transfusions are probably bad for you
• Perhaps there are better guides to transfusion practice during cardiac surgery
• Lets consider Goal Directed Perfusion and its effect on transfusion practice
Annals of Thoracic Surgery 2005;80:2213-20
Acute Kidney Injury and DO2
Ranucci et al, Oxygen Delivery During Cardiopulmonary Bypass and Acute Renal Failure After Coronary Operations,Ann Thorac Surg 2005,; 80; 2213-2220
n=640
n=53
n= 113
n=242
0%
1%
2%
3%
4%
5%
6%
7%
High HCTHigh DO2
Low HCTHigh DO2
High HCTLow DO2
Low HCTLow DO2
Renal Replacement- Acute Renal Failure Occurrence (%) N =1048 pts
High DO2
Low DO2
< 270 mlO2/min/m2
Independent of whether you have a low
or high hematocrit
Low Oxygen Delivery more predictive of ARF
• The point where oxygen consumption becomes dependent on oxygen delivery
• Oxygen extraction increases
• Accumulation of oxygen debt
• Development of lactate
• Aerobic-anaerobic threshold
Standardized perfusion approach - Pump flow based on BSA
• Patients with same BSA, but very different physical characteristics may receive the same pump flow
• They might have different oxygen delivery (DO2) needs
Described by Galletti in 1962
[Galletti PM, Brecher GA. Heart –lung bypass, principles and
techniques of extracorporeal circulation. New York: Grune &
Stratton, 1962.
• Based on “fictional” patient of 175 cm, 70 Kg, 1.84 BSA, basal VO2 of 240 ml/min.
• Ranked as: • High-2.4l/min/m2
• Medium-1.8 l/min/m2
• Low 1.1 l/min/m2
How do you define adequate perfusion?
G OA L
• 2.2 to 2.6 l/min/m2 adjusted for temperature
• Mean arterial pressure > 50 mmHg
• SvO2 > 65%
• Lactate < 2 mmol/l
PR O B L E M
• Does not account for changes in hemoglobin
• Regional dysoxia not reflected in global SvO2 measurements
• Delayed perfusion response to lactate monitoring
Goal Directed Perfusion (GDP)
• Oxygen delivery (DO2i) > 262 mL/min/m2
• 65 % reduction in acute kidney injury
• Oxygen delivery to carbon dioxide production index
• DO2i / VCO2i
• > 5.3 = 40% reduction in AKI
• Measure of global oxygen delivery to metabolic rate
DO2 DO2i/VCO
2i HCT
Why is renal function a good marker of perfusion adequacy?
• Renal oxygen extraction rate low (10%) therefore very sensitive to oxygen delivery mismatch
ExpCO2 x Gas Flow
(Cardiac Index) x (Hgb) x 13.4
DO2
VCO2
VO2
OXYGEN DERIVED VARIABLES (DO2i and VO2i)
ALONG WITH
CARBON DIOXIDE PRODUCTION VARIABLES
(VCO2i)
ARE THE BEST PARAMETERS TO MEASURE THE
METABOLIC RESPONSE DURING CPB
DO2i > 280 mL/min/m2
DO2i/VCO2i > 5.0
Sorin CONNECT™
UCH : Started investigating GDP in 2012, 100% use July 2014
How do we use GDP information PA R A ME T ER
• Oxygen Delivery Index
(DO2i) • Manage hemoglobin flow
• Oxygen Consumption (VO2)
• Carbon Dioxide Production
Index (VCO2i)
• DO2i / VCO2i ratio *
G OA L S/ INT E R ACTIO NS
• > 270 ml/min/m2 • Depends on DO2i /VCO2i
• Global metabolic rate • Anesthesia level • Oxygenator management
• Result of aerobic/anaerobic metabolism
• Oxygen delivery adequate to support current metabolic demand • > 5.0
Lessons Learned @ UCH
• Oxygen delivery and end organ function
• PRBC transfusion science
GDP and AKI
• July all type AKI rate = 25%
• March all type AKI rate = 8.1 %
• Nadir DO2i
• July = 247 mlO2/min/m2
• March = 289 ml O2/min/m2 0
5
10
15
20
25
0
50
100
150
200
250
300
350
JUL AUG SEP OCT NOV DEC JAN FEB MAR
ml O
2/m
in/m
2
Oxygen Delivery and AKI
nadir DO2 Mean DO2 nadir DO2/VCO2
AKI Rate Linear (nadir DO2) Linear (AKI Rate)
Does every transfusion improve tissue respiration?
69 (5.7)
75 (5.3)
79 (3.6)
75 (1.7)
Efficacious Non-Efficacious
SvO2 Response to Transfusion
Pre SvO2 Post SvO2
p < 0.001
p = NS 44.4
(23.3)
0.82 (13.9)
Efficacious Non-Efficacious
Change in Oxygen Extraction Ratio (EO2)
delta EO2
p < 0.001
0
5
10
15
20
25
30
35
40
45
50
Control GDP Control tx GDP tx
%
New AKI %
p < 0.001
Low DO2i Avoidance is critical
• If you avoid the low oxygen delivery state, even with a PRBC transfusion the AKI rate is significantly reduced
• PRBC transfusion on CPB should be based on:
• High oxygen extraction
• Inability to increase DO2i with flow
• Low DO2i / VCO2i ratio
• Continuous surgical loss of hemoglobin
• Challenges all the PRBC and low hematocrit outcome data
Effect of Goal Directed Perfusion (GDP) on PRBC Transfusion during CPB
• Baseline PRBC Transfusion Rate
• 46%
• Volume mean 2.8 units
• End of December 2014 PRBC Rate
• 20%
• Volume mean 0.6 units/patient
• 50% reduction in frequency of PRBC
• 77% reduction in volume of PRBC units
0
5
10
15
20
25
30
35
40
45
50
2013 Q3 2013 Q4 2014 Q1 2014 Q2 2014 Q3 2014 Q4
PRBC Utilization Rate
• Low oxygen delivery to carbon dioxide production ratio (nadir DO2i / VCO2i ) < 5 is more predictive of global oxygen demand mismatch than nadir DO2i or SvO2 alone.
• The DO2i / VCO2i ratio should be considered when selecting an appropriate flow rate for each patient.
• Early detection of low oxygen delivery reduces the incidence of AKI
• Average time below DO2i < 270 in all patient groups with AKI was 37 minutes
• Continuous monitoring of ALL GDP parameters is important
• Most at risk
• Female, low pre-bypass intraoperative hemoglobin, reduced circulating blood volume
GDP: Take Home Points
Concluding thoughts: Anemia
• Complex – multifactorial issue
• Likely has implications on mortality and morbidity
• Being more specific in identifying disease specific needs for transfusion critical.
• Discussion???
Thanks!
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