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!