Transcript CTx - SHAC QA

Anesthesia for Cardiac Surgery
Jonathan Parmet M.D.
Society Hill Anesthesia Consultants
Case Discussion
• 52 year old morbidly obese female
scheduled for CABG
• she has normal ventricular function
• she has 100% LAD occlusion not amenable
to coronary stenting
• Has a history of NIDDM, and HTN
Case Discussion
• What anesthetic monitors ?
– PA catheter?
• Should the patient be fast tracked ?
• What are the anesthetic considerations?
– Push for extubation on the table?
Overview
• Anesthetic monitoring
– PA catheter
– Transesophageal echocardiography
– Cerebral oximetry
• Anesthetic for Patients with CAD requiring
cardiopulmonary bypass
• Pharmacologic agents administered
• Fast track
Open Heart history
Philadelphia’s role
• 1948-Boston/ Philadelphia- Dwight Harken/
Charles Bailey- beating heart mitral
commisurotomy
• 1952- Minnesota- Lillehel/Lewis- Hypothermia
(based on work by Bigelow)- open heart withclamping venous inflow to heart• 1953- Philadelphia-Gibbons- TJH first successful
use of CPB with oxygenator
• 1955- Mayo clinic- bubble oxygenator
Monitors
• Large bore IV- 18-16 gauge
• Invasive arterial monitoring right radial,
brachial, or femoral
• Pulmonary arterial catheter – mixed
venous, continuous cardiac output
• Trans-esophageal echocardiography
• Cerebral Oximetry
• Bis
Pulmonary Arterial Catheter
• Used for cardiac filling pressures, tissue
perfusion (mixed venous sat), cardiac
output
• Outcome studies do not support the use of a
PA catheter
– Connors ( JAMA 1996) – increased morbidity
in ICU patients with PA catheters vs no PA
cath
– Schwann Anesth Analg. 2011 Nov;113(5):994-1002.
Lack of effectiveness of the pulmonary artery
catheter in cardiac surgery.
Anesth Analg. 2011 Nov;113(5):994-1002
Anesth Analg. 2011 Nov;113(5):994-1002
Study Assertions
• Increased morbidity in patients with PA
catheter
• Increased use of inotropes in PA group
• Increased fluid administration in PA group
• PA catheter not confer any beneficial effect
in the CABG population – might be harmful
?
Anesth Analg. 2011 Nov;113(5):994-1002
Limitations
• Data collection > 10 years old
– How applicable to patients today
• Variations in institution use from 1-99%
• Medications not included in propensity
matching– beta blockers and statins, anti
hypertensives, aprotinin (?)
• Despite propensity matching Bias that
patients with severe disease received
catheters
• TEE patients not included
How do PA catheters increase
morbidity?
• Complications of insertion, arrhythmias,
pulmonary hemorrhage, infection- not
reported
• 3% increase in fluid 200 ml, 7% increase in
fluid balance 200 ml, 8% increase use of
inotropes
• Increased morbidity due to
misinterpretation of information
Anesth Analg. 2011 Nov;113(5):994-1002
Benefits of Transesophageal
Echocardiography
Monitor LV function
Assess intravascular volume status
Assess myocardial ischemia/ dysfunction
Valve function
Intracardiac defects
Aortic pathology
Unexplained cardiovascular deterioration
Detect new wall motin abnormalities
Guidelines for Perioperative Transesophageal EchocardiographyAn
Updated Report by the American Society of Anesthesiologists and the
Society of Cardiovascular Anesthesiologists Task Force.
Anesthesiology:May 2010 - Volume 112 - Issue 5 - pp 1084-1096
Transesophageal Echo in Myocardial
revascularization: Influence on intraoperative
decsion making. Leung A&A 1996
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75 cases
584 interventions
TEE single most guide in 17%
TEE guided fluid therapy in 30%
Vasopressor guide in 3%
Not an outcome study- Does not define
patients do better with TEE monitoring
Intraoperative Echocardiography is indicated in
High-risk coronary artery bypass grafting.Ann
thoracic Surg. Savage 1997
• 82 high risk CABG patients
• 33% one major surgical intervention based
on echo
• 51% one major anesthetic/hemodynamic
change
• No improved outcomes with TEE
– 3 patients detected severe atherosclerosis of
Aorta off pump
– 6 patients alternative cannulation sites
– 16 patients undiagnosed valve disease
The role of intraoperative transesophageal
echocardiography in patients having CABG.
Ann Thorac Surg 2004 Qaddoura
• New prebypass findings in 10%
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PFO in 22- 7 closed
Sig MR, TR, AR 12- repair in 5
AV (lambl’s) 2- AV explored
Aortic Atheroma 5- op cab
• Surgical plan altered in 3.4%
• New Postbypass in 3.2%
– New mr 3 – repair 2
– Depressed LVF 6- IABP placed- 5
Case Discussion
• 57 year old male for redo-CABG. h/o
IDDM, hyperlipidemia, obese
• 10 hour surgical procedure/ 3 hour pump
time/ 2 hour cross clamp
• Post-op – called to see patient for occipital
alopecia
• 3 years later complains of inability to
concentrate and perform his tasks as an
accountant
• Files law suite for having received head
trauma during surgical procedure
Neurologic changes associated
with Cardiopulmonary bypass
• 3-5 % of CPB suffer perioperative stroke
• 30-50% of CPB suffer neuro-cognitive
dysfunction
– The incidence varies with the type of neuro
psychological testing
Adverse Cerebral Outcomes after Coronary
Bypass Surgery NEJM 1996 McSPI
• N= 2108
• Type I- Stoke stupor
• Type II- deterioration in intellectual
function, memory deficit
• 3.1% type I, 6.1% type II
• 21% type I died vs 10% type II
• Incidence increased in patients > 70 yrs
NEJM 1996
Factors Associated with Adverse
Neurologic Outcome
• Advanced Age
• History of previous neurologic event
• Low flow (Cerebral saturation measure of
oxygen extraction
• Hypertension
• DM
• Atherosclerotic Disease
• Open chamber procedures
• Use of Cardiopulmonary Bypass
Etiology of Adverse Neurologic
outcome
• Embolic
– Microemboli (CPB)
– Macroemboli ( aortic manipulation Aortic cross
clamp and cannulation )
• Hypoperfusion
– Carotid Stenosis (increased incidence in DM)
– Microvascular stenosis (increased incidence in
females and DM)
Strategies to minimize emboli/ factors affecting
cerebral blood flow
• Minimize aortic manipulation
– Single clamp technique
– Off pump CABG (OpCAB)
• Maintain cerebral blood flow
– Maintain higher perfusion pressure
– Blood gas measurement
• Decrease CMO2– Temperature (80’s-90’s hypothermia 24 degrees)
late 90’s til now moderate hypothermia during
cpb
– Anesthetic agents (propofol, Ca channel blockers
Does cardiopulmonary bypass contribute
to neurologic dysfunction?
• Ann thorac Surg 2003
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N= 52, 29 opCAB, 23 onCPB
TCD, CMRI, Neuropsych testing
opCAB less emboli than on CPB
No difference cognitive decline 3 months after
surgery
Cognitive and Cardiac outcomes 5 years
after off pump vs on pump CABG
• JAMA 2007
– 231 low risk CABG (123 opCAB, 117 onCPB)
– Measure Cognitive status after 5 years
– 62/123 (50.4%) opCAB, 59/117 (50.4%) on
CPB cognitive decline
In low-risk CABG patients, avoiding the use of CPB had no
effect on 5 year cognitive decline
Is it aging?
• A 25-30% cognitive impairment has been
demonstrated in the older major vascular,
orthopedic, and thoracic surgical
populations Lancet 1996
• What is the effect of bypass versus the
effect of aging?
Cerebral oximetry
• Monitor for cerebral ischemia
– Near Infrared- 70% venous/ 30% arterial
• 3-5 % of CPB patients suffer perioperative
stroke
• There is patient to patient baseline
variability
Cerebral Oximetry
Lower baseline levels associated with
increased patient morbidity and mortality
( Murkin Anesth & analg 2007, Heringlake
Anesthesiology 2011)
Indirect measure of tissue perfusion not just
cerebral perfusion
Murkin. Anesth & Analgesia 2007
Murkin. Anesth & Analgesia 2007
Murkin. Anesth & Analgesia 2007
Murkin. Anesth & Analgesia 2007
Interventions
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Check head insure in neutral position
PaCO2< 35 Increased to > 40mmHg
If MAP < 50 increased > 60
If CVP > 10
If cardiac index < 2.0 (CPB) increased > 2.5
Persistent decrease Increase FIO2/ pulsitile
pressure/ propofol 50-100/ transfuse if hct <
20%
Preoperative Cerebral Oxygen Saturation
and Clinical Outcomes in Cardiac
Surgery
Anesthesiology:January 2011 - Volume 114 - Issue 1 - pp 58-69
Cerebral Desaturation Algorithm
• Increase FIO2 to 100%
• Assess head and cannula position
• If PaCO2 < 40 mmhg increase to > 40
mmhg
• Increase MAP > 60 mmhg
• If Hct < 20 % consider transfusion of PRBC
• Increase anesthetic depth
Case Presentation
• 57 yr old female for CABG/ Mitral valve
annuloplasty
• A-line/ large bore IV/ PA catheter/ TEE/
Cerebral Oximeter
• Induction of anesthesia- 100% oxygen,
sevoflurane/ 250-500 microgms fentanyl/ 14 mg midazolam/ 10 mg vecuronium
Anesthesia objectives for patients
undergoing cardiopulmonary bypass
• Anesthesia
– Analgesia
• Narcotic (fentanyl 10-20 micrograms/kg)
• Amnesia (midazolam- 1- 5 mg)
• Inhalation agents ( desflurane, sevoflurane,
isoflurane)
– Muscle relaxation
• Long acting Nondepolarizing muscle relaxant
pancuronium ( no longer available)
Intermediate acting nondepolarizing muscle relaxant
Principles of Anesthetic: Major
Determinants of Myocardial Oxygen
Consumption
• Heart rate
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Increases in heart rate
increase contractility
Increase oxygen consumption
Decrease myocardial oxygen supply
• Contractility
• Wall tension
– Law of Laplace
Ischemic preconditioning
- Cath lab- PTCA- human observation of ischemic
preconditioning
– 1st balloon inflation ST-segment elevation with chest
pain
– 2nd balloon inflation- reduction in ST-segment with
decreased chest pain
– A small period of sub-lethal ischemia prior to a prolong
period of ischemia induces a complex series of
reactions which reduces myocardial injury
• adenosine and bradykinin activate G-proteins in the
myocyte pathways in turn activates complex cascade
(open KATP channels, protein kinase C, (-) guanine
nucleotide, ROS) - Tanaka K. Mechanisms of
cardioprotection by volatile anesthesthics. Anesthesiology
2004, 100:707-21
Effects of sulfonylureas on
Ischemic preconditioning
Ischemic Preconditioning
The Inhalational Anesthetics
• Sevoflurane
– Most data on sevoflurane
• Isoflurane
– Kersten JS. Isoflurane mimics ischemic preconditioning via
activation of KATP channels. Anesthesiology 1997;87:1182-90
• Desflurane
No study favor one volatile agent over another. Maintain
volatile anesthetic throughout the procedure
De Hert SG. Effects of propofol, desflurane, and sevoflurane
On recovery of myocardial function after coronary surgery.
Anesthesiology.2003;99:314-23
De Hert SG. Effects of propofol,, and sevoflurane
On recovery of myocardial function after coronary surgery.
Anesthesiology.2003;99:314-23
Myocardial damage prevented by volatile anesthetics
Journal cardiothoracic and Vascular Anesthesia 2006
Glucose control for Cardiac
Surgery
• Maintain tight glucose control
• Blood sugars < 180 mg/dl
• If > bolus between 2-3 units regular (short
acting) insulin
• CPB associated w/ increase in blood
glucose
Blood glucose control in patients
undergoing cardiac surgery
• Elevated blood glucose levels in patients with
myocardial infarctions have a 30% worse outcome
• Elevated blood glucose implicated in worsening
the severity of stroke
• The society of thoracic surgeons guideline series:
Blood glucose management during adult cardiac
surgery 2009
• Higher glucose levels during and after cardiac
surgery independent predictor of mortality
Case Discussion
• 51 year old male for CABG. Severe 3 vessel
disease. History of increased cholesterol
• Intraoperative sugars prior to CPB normal
• Sugars on CPB increase to 200 gm/dl
• Should the blood sugar be treated?
• What if the sugar was 145?
Deleterious effects of
hyperglycemia
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Increases myocardial infarction size in dogs
Inhibits ischemic preconditioning
Amplifies reperfusion injury
Produces coronary endothelial dysfunction
facilitating myocardial ischemia
• Inhibits neutrophils
• Positive effects of Insulin
– Decrease free fatty acids and decreases free
radical formation
• Fish – 200 patients undergoing coronary
artery bypass grafting (2003)
– Postop glucose > 250 mg/dl => 10 fold increase
in complications
• Gandhi- 400- retrospective cardiac surgeryelevated blood glucose independent
predictor of poor outcome (2005)
Intensive Insulin Therapy in Critically Ill
Patients N Engl J Med 2001; 345:1359-1367
Van de Berghe
• Prospective randomized to intensive
treatment (bs- < 110 mg/dl) conservative
treatment (bs- 180-200 mg/dl)
• Pt population 59% CABG, 27% Valve, 14%
combined procedure
• 39% intensive hypo, 6% hypo
• The key point is Blood glucose control not
occur intraoperatively, only on admission to
the unit
Intensive Insulin Therapy in Critically Ill
Patients N Engl J Med 2001; 345:1359-1367
Continuous insulin infusion reduces mortality in
patients with diabetes undergoing coronary artery
bypass grafting. J thorac Card Surg 2003;125:100721 Funary
• CABG- n=3554
• 1987-1991 subcut insulin (n=942)
• 1991-2001 Continuous infusion
– 1991 to 1998 target sugar- 150-200 mg/dl
– 1999- 2001 sugar 125-175 mg/dl
– 2001- sugar 100-150
Funary J thoracic and Cardiovascular Surgery
2003
• Overall mortality 388/ 3554 =2.8%
• Mortality in Sub Cut =4.5% 40/942
• Mortality in Continuous infusion = 1.6%
– P<0.05
• Conclusion: improved blood sugar control
improve overall mortality
– ? Which blood glucose range
No Caption Found
Furnary, A. P. et al.; J Thorac Cardiovasc Surg 2003;125:1007-1021
Copyright ©2003 The American Association for Thoracic Surgery
Tight Glycemic control in diabetic coronary
artery bypass graft patients improves
perioperative outcomes. Lazar Circulation
2004
• N= 141 patients
• Randomized to tight control GIK solution
– Target blood glucose 125-200 mg/dl
• Subcuntaneous Injections
– Blood glucose < 250 mg/dl
• GIK started before CPB, but discontinued
on CPB- restart with Aortic unclamped
• Continued 12 hrs postop
Figure 4. Cardiac index.
Lazar H L et al. Circulation 2004;109:1497-1502
Copyright © American Heart Association
Poor intraoperative blood glucose control associated
with a worsened hospital outcome after cardiac
surgery in diabetic patients. Anesthesiology 2005
• N= 200
• Maintain intraop blood glucose 150<to
<200 mg/dl
• Insulin infusion started intraop
• Postop maintain blood glucose < 140 mg/dl
• 71 patients had intraop insulin infusion
• 35 patients uncontrolled sugars
Poor intraoperative blood glucose control is
associated with a worsened hospital outcome after
cardiac surgery in diabetic patients. Ouattara
Anesthesiology 2005;103:677-8
Intensive versus convention glucose management in
the critically ill. The Nice-sugar investigation. NEJM
2009
• N= 6104
N= 3050 conventional N= 3012 intensive
• 206 of the intensive rx group had severe
hypoglycemia
• 15 in the conventional group had severe
hypoglycemia
• 27% intensive group died *
• 24.9% conventional group died *
• Intensive glucose control
– 81-108 gm/dl
• Conventional glucose control
< 180 gm/dl
Non surgical population- different treatment protocol- high incidence
Of hypoglycemia in intensive group
Conclusions
• Elevated blood glucose preop is associated
with poor outcomes postop
• Intraoperative insulin infusions reduce
mortality in the postoperative period
(perhaps)
• During CPB insulin administration if Blood
glucose > 140
• Continue infusion in the postoperative
period
Blood Conservation in Cardiac
Surgery
• Case conference November 2, 2012
Case Presentation
• 76 year old male for CABG (1 bypass) and
mitral valve repair. He has Aortic
insufficiency ( mild to moderate). He
appears frail. Pre op platelet count is 100K
• Undergoes 1 vessel bypass/ Mitral valve
repair. After chest closure chest tube
drainage at 300 for one hour. No thrombus
in the chest tube
• Second Hour 200 cc of chest tube drainage
Case
• Transfused 5-7 units PRBC, 12 units FFP,
18 units Platelets, cryo, Recombinant Factor
VII (90 ug/kg)
• Lowest intraoperative Hgb 6 gm/dl
• After 4 hours chest tube drainage decrease
• TEE no evidence of tamponade
• 2 days postoperative chest X-ray reveals
ARDS
• Aggressive diuresis chest X-ray resolves
• Does packed red blood cell transfusion
affect patient outcome independently?
• Does the number of packed red blood cells
administered affect patient outcome?
• Does blood component therapy affect
patient outcome?
ASA refresher course 2012
Background
• 30% of patients post cardiopulmonary
bypass develop microvascular bleeding
• 10% of hospital transfusions are allocated to
patients cardiac surgical patients
• 34%-50% of CABG patients are transfused
• However significant risk is associated with
allogenic red blood transfusions
Transfusion in Coronary Artery Bypass
Grafting is Associated with Reduced LongTerm Survival Ann Thorac Surg
2006;81:1650-1657
• N= 10,289 isolated CABG patients
• 1995-2002
• 49% of patients received PRBC
– Est 5,041 transfused
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9.8 % Platelets
2.8% FFP
0.5% Cryo
2,067 deaths
Koch. Transfusion and long-term
survival. Ann Thorac Surg 2006;81;1650
Koch. Ann Thorac Surg 2006;81:1650-7
Conclusion
• Perioperative PRBC transfusion is
associated with adverse long-term sequela
in isolated CABG. Attention should be
directed toward blood conservation
methods and a more judicious use of
PRBC.
• With increased units of PRBC there was an
increase in patient mortality
Criticism
• Observational study
– Not randomized
– No indication of transfusion trigger
– Blood transfusions could be the cause or just a
marker of patients that were sicker and had a
tendency to bleed
• Included in analysis greater than 2 PRBC
The Association of perioperative red blood cell
transfusions and decreased long term survival after
cardiac surgery. A&A 2009. 1741-46 Surgenor
• Northern New England Cardiac disease
group
– 8 medical centers
• 9,079 CABG 2001 to 2004
• 36% of patients PRBC 1-2 units
• Risk factors for transfusion
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Increasing age
Anemia
Female (decreased BMI)
Co-morbid disease
Figure 1. Adjusted survival by red blood cell use.
Surgenor S D et al. Anesth Analg 2009;108:1741-1746
©2009 by Lippincott Williams & Wilkins
Conclusion
• “ For anesthesiologists and cardiac
surgeons, transfusion of just 1 or 2 units is
often viewed as minor and routine decision”
– That decision places patients at significant risk
• Exposure of 1 to 2 units of PRBCs was
associated with a 16% increased hazard of
decreased survival after cardiac surgery
Why?
• Shelf life of PRBC = 42 days
• 20-40% of PRBC > 28 days
• Could prolonged storage time be associated
with increased morbidity and mortality?
– In Cardiac patients increased risk of death,
renal dysfunction ,respiratory dysfunction and
ICU
– PRBC greater than 28 Days undergo
conformational changes
Stored PRBC changes
• Post operative infectious process
– Inhibition of immune system (non leukocyte
washed)
Damage of the microcirculation from
transfused Packed RBCs that have abnormal
morphology
Long term inhibition of the recipients immune
function
Stimulation of the inflammatory response
Duration of Red-Cell Storage and
Complications after Cardiac Surgery. N
Engl J Med 2008; 358:1229-1239. Koch
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2872 CABG 14 day PRBC from 1998-2006
3130 CABG >14 days (old blood)
Mean storage for 14 day blood- 11 days
Mean storage for old blood- 20 days
Duration of Red-Cell Storage and Complications
after Cardiac Surgery. N Engl J Med 2008;
358:1229-1239
• PRBCs stored greater than 14 days had
increased risk of perioperative complications
and reduced short term and long term
survival
Respiratory failure, septicemia, renal failure,
and multisystem organ failure.
Duration of Red-Cell Storage and
Complications after Cardiac Surgery. N Engl
J Med 2008; 358:1229-1239
Duration of Red-Cell Storage and
Complications after Cardiac Surgery. N Engl
J Med 2008; 358:1229-1239
Duration of Red-Cell Storage and
Complications after Cardiac Surgery. N Engl
J Med 2008; 358:1229-1239
• Greater in hospital mortality
– 2.8% vs 1.7% older vs newer
• More likely develop renal failure
– 2.7% vs 1.6 % older vs newer
• Septicemia
– 4.0% vs 2..8% older vs newer
• Multisystem organ failure
– 0.7% vs 0.2%
Reasons for increased morbidity and
mortality
• Conformational changes decreases PRBC
viability
• Decreased deformability results in
impairing microvascular flow
• Decrease 2-3 DPG - decrease oxygen
delivery
• Increased adhessiveness and aggregabilty
• Decreased nitric oxide and accumulation of
proinflammatory substances
Questions
• How can we reduce blood transfusions?
– Blood conservation strategies
• Does component transfusion carry the same
risk?
– Platelets
– Fresh frozen plasma
– Cryo
Coagulation and Cardiopulmonary
Bypass
Case Presentation
• 50 year old male for redosternotomy along
with revision aortic root replacement. He
has severe aortic insufficiency
• Receives 300 units / kg of Heparin with
targeted ACT > 400
• Duration of Cardiopulmonary Bypass =
4hrs
• Off CPB 1:100 reversal of protamin
• ACT returns to baseline
Case Presentation
• No thrombus is formed and the patient
demonstrates diffuse microvascular
bleeding
• Receives empiric 4 units of FFP / 2 (6)
packs of platelets- continues to bleed
• Receives cryoprecipitate
• Receives Recombinant Factor VII (45
ug/kg)
• Receives Prothrombin Concentrate (45
units/kg)
Overview
• Coagulation Cascade
– Classic Coagulation Cascade
– Current Depiction of In vivo clot formation
• Cardiopulmonary Bypass and effect on the
Coagulation Cascade
• Anticoagulation for Cardiopulmonary
bypass (measure of anticoagulation)
• Reversal of anticoagulation
– Measure of reversal of anticoagulation
Coagulation Cascade
• Classic coagulation Cascade
Intrinsic Pathway
Extrinsic Pathway
• 2 phase Model of Coagulation
– Initiation Phase
– Propagation Phase
Waterfall / cascade model of
Coagulation
Utility of Classic Cascade
Not an adequate representation of in vivo
events
• Dovetail with coagulation tests: prothrombin time (PT, extrinsic) and activated
partial thromboplastin time (aPTT intrinsic)
• Also helps explain factor deficiencies
(hemophilia) and effect of anticoagulants
(coumadin, heparin) with respect to
coagulation tests
Question
• Can you have a normal ACT with an
abnormal PT and Normal PTT ? i.e. defect
in extrinsic pathway
• Can you have a normal ACT with
abnormal PTT and normal PT ? i.e. defect
in intrinsic pathway
Waterfall / Coag Cascade
• Intrinsic or contact pathway has no role
in early events in clotting in vivo.
• The end result of the intrinsic and extrinsic
pathways: prothrombin cleaved to thrombin
=> fibrinogen to fibrin.
• However thrombus formation is a much
more dynamic process involving platelet
activation and adhesion, interacting with
coagulation factors,VonWillebrand factor,
Ca++
Basics of Coagulation
• Platelets are bound to sites of injury, they
serve both to localize and to accelerate the
soluble coagulation process i.e. activate
factors
• Thrombin generated during the initiation
phase potently Activates Platelets
2 Phase Model of Coagulation
Initiation phase
Platelets+Tissue Factor + VIIa+ = Extrinsic Xase=> Xa and
IXa
Factor Va-XaCa++(prothrombinase) +
platelets=>
small amounts of thrombin
IIa cleaves VIII + V + IX =>
intrinsic Xase=> 30 increase in
thrombin generation
• AS a result of the intrinsic Xase- Explosive
thrombin generation results and produces
enough fibrin to stabilize clot formation
Initiation Phase
• TF-VIIa (extrinsic Xase)=> Catalyzes X to
Xa => which complexes on the platelet with
factor Va small amounts of thrombin
• Thrombin then initiates the propagation
phase which ends in explosive generation
of thrombin and fibrin gel
• Most lab tests only address the initiation
phase
Propagation Phase
• Thrombin generated in the initiation phase
potently activates platelets along with
cleaving factors VIIIa, and Va
• Prior to this Factor VIII complexed with
VWF is released and activated to complex
with factor IX forming an enzymatic
complex (intrinsic Xase) which generates
Xa
• 50 fold increase in thrombin production
• Factor XI further amplifies the reaction
Clot Architecture
• Amplification of thrombin generation
permits the formation of fibrin clot
• Clots vary in fibrin thickness
• Paradoxically thicker clots have more
permeability between fibrin strands making
them more susceptable to lysis
• Thin clots develop a more occlusive
network
Clot Architecture
• High thrombin clots have tighter crosslinking and are more resistant to lysis
• Low thrombin clots have less cross linking
and are susceptable to lysis
• High fibrin concentrations also more
resistant to lysis
• Low fibrin concentrations more susceptable
to lysis
Conclusion
• Disruption of the endothelium (EC) => TF
initiates the coagulation system along with
platelet activation/adhesion which forms a
platelet plug and starts the process of clot
• End pathway prothrombin- thrombin (II)
Fibrinogen- fibrin (I)
• Fibrin strands cross link to form clot
Review
• Initiation Phase
– Extrinsic Xase- TF- VII- plt=> Xa =>IXaVa=> IIa
• Propagation Phase
– Intrinsic Xase- VIII-IX=> Xa=> Va=> Iia
– Prothrombinase Xa+Va=>explosive thrombin
• In order to form thrombus need platelets for
activation of coagulation factors
Normal hemostasis. 1, Initial plug formation begins with von Willebrand factor (VWF) binding
to collagen in the wound and platelets (plt) adhering to VWF. 2, Coagulation is initiated by
small amounts of active factor VII (FVIIa) in blood binding to the expo...
Sniecinski R M , Chandler W L Anesth Analg
2011;113:1319-1333
©2011 by Lippincott Williams & Wilkins
Arterial Clot vs Venous Clot
• Arterial thrombus formation relies heavily
on acute platelet plugging
– Anticoagulants for arterial thrombus attack
platelet function- ADP
inhibitors/phosphatidylserine ( clopidorel,
ticagrolar), GP IIa/IIIb inhibitors
• Venous thrombus formation relies heavily
on thrombin generation (Coumadin, heparin
pradaxa)
Platelets 3 A’s
• Activation and formation of platelet /
platelet bonds
• Adhesion to endothelium
• Aggregation
Platelets
Platelets must activate and adhere to the
injured vessel nearly instantaneously
• platelet–coagulation factor interactions
culminate fibrin formation
• Most potent platelet activator?
Protease Activated Receptor-1
PAR-1
Platelets
• Platelet Activation
– Shape change-Change in shape from
Sphere to disc to finger like projections
– Exposure and activation of GPIb and GP
IIb/IIIa permit binding of fibrinogen and
platelet adhesion to the exposed vessel
wall
– Dense granules (ADP, TA-2 and
Serotonin) and alpha granules (growth
factor, PF-4 and fibrinogen, VWF)
migrate to center and then periphery
Dense Granule Release
• ADP- potent stimulant to attract other
platelets for aggregation
• Thromboxane-A2- platelet attraction and
also vasoconstriction
• Serotonin- platelet attraction and
vasoconstriction
Platelet Activation major goals
• recruitment of additional platelets
• vasoconstriction of smaller arteries to slow
bleeding (Thromboxane, serotonin)
• local release of ligands to stabilize platelet–
platelet matrix
• localization and acceleration of platelet
associated fibrin formation
• protection of clot from fibrinolysis
Adhesion and Activation
Platelet Adhesion under shear
stress
Platelet Adhesion
– VwF affinity to GPIba slows the platelet
down and has the platelet change from
sphere to disc.
– At same time platelet activated and
GPIIb/IIIa changes and binds to VWF
– Platelet covers endothelium
Platelet Aggregation
• Release of alpha and dense granules
contents
– ADP, Ca++, serotonin, thromboxane A2
• Recruits other platelet
• GPIIb/IIIa change and permit growth of
platelet plug
Platelet Aggregation
• platelet–ligand–platelet matrix in which
fibrinogen or vWf serves as the bridging
ligand
• GPIIb/IIIa is the most abundant
glycoprotein on the platelet surface
• activated platelets provide specific receptors
for factors VII, VIII, Xa, IXa, and Va
Factor XIII
• Factor XIIIa stimulated by thrombin
• bind to fibrin and stabilizes fibrin and cross
links with fibrin to stabilize clot
• Binds antiplasmin to prevent clot lysis
• Clot less likely to be dissolve
Endogenous Anticoagulants
• Directed at inhibiting Platelets
– Arterial circulation
• Directed at inhibiting thrombin
– Venous circulation
Endogenous anticoagulants
Arterial
• Endothelial Cell surface carries a net
negative surface charge
• nitric oxide and prostacylin (PGI2) inhibit
platelet clot (adhesion and aggregation)
• Healthy endothelial cells also synthesize
ADPase (inhibits Platelet aggregation)
Endogenous Anticoagulants
venous
• Endothelial cells synthesize an endogenous
heparin congener, heparan sulfate works
via antithrombin III => X, IX, XI,II
• Activated protein C (APC) cleaves factors
IXa and VIIIa, thereby down regulating
thrombin formation (also anti inflammation)
• Tissue factor pathway inhibitor (TFPI)
cleaves Tf-VII
Tissue Plasminogen Activator
• Thrombin, and Xa stimulate release of t-PA
– Cleaves plasminogen to plasmin
– Release of fibrin split products (D-dimer)
– Effect of TPA blunted by plasminogen
activator inhibitor
• Also Thrombin Activator Fibrinolysis
Inhibitor (plasmin or thrombin for stimulus)
Fibrinolysis
Summary
• Denuding the endothelium results in release
of tissue factor which activates factor VII
platelets and thrombin (initiation Phase or
the extrinsic pathway)
• Denuding the endothelium results in
cleaving serine protease and activation of
platelets, XII which stimulates the intrinsic
pathway
• Both pathways result in thrombin then
cleaving fibrinogen to fibrin
CPB: Upsetting the balance
• Heparin
– Paralysis of the coagulation cascade by heparin
•
•
•
•
•
•
Hemodilution
Hypothermia
Coagulation cascade
Platelet defect
Complement system
Leukocyte Activation (inflammatory
Response)
Heparin
• Variability on its effect from patient to
patient (as measured by the Act)
• Stimulates ATIII (1,000 fold)
– Inhibits II, Xa, IX, XI
• Inhibits Platelets (direct, indirect)
– VWF effect on GP1b receptors
– No effect on GP IIb/IIIa
• Bound to protein and sequestered into the
endothelial cells – mechanism of heparin
rebound
Hemodilution
• Pump Prime- 1 to 2 L of crystalloid
• Hematocrit decrease from 40 to 25%
• Coagulation factors decrease 60-70%
– Factors II, V, fall significantly and factor II
correlate with post op bleeding
• With increased duration of CPB factors
decrease further due to activation on CPB
Changes in Coag factors before
and after bypass
Fall in thrombin potential and
increased chest tube drainage
Hypothermia
• 100 decrease in temperature results in 50%
inhibition of enzymatic activity
• 33-37 nonsignificant reduction in
coagulation enzyme activity below 33 sig
• Temperature of 320C inhibits platelet
activation and aggregation by thrombin
• Fibrinolysis not inhibited by <330 C
Activation of
Coagulation Cascade
• CPB induces contact activation
• Auto cleave Factor XII =>preKallikrein
=> Kinins ( bradykinin)
– Intrinsic coagulation cascade=> thrombin and
fibrin and EC => TPA
• TF initiator of clottting (dominant source of
clotting factor activation)
• Intense thrombin and fibrin generation over
the first 5 min despite maximal
heparinization (ACT > 480)
• 5 minutes of CPB thrombin and fibrin levels
increase 20 fold
• Soluble Thrombin/Fibrin not circulate in
blood- thrombin/fibrin measured is non
hemostatic
• Total fibrin reduced on bypass (heparin)
• After reperfusion increase in thrombin/ and
fibrin increase
CPB
Platelet dysfunction
• CPB decreases plt count beyond amount
attributed to hemodilution
• CPB-induced functional platelet defects
may produce bleeding that requires platelet
transfusion despite seemingly adequate
platelet counts
• CPB activates platelets, (release of the
contents of internal granules alpha and
dense)
Post CPB Platelet dysfunction
• Blunted response to stimulation (in vitro)
• Higher concentrations of thrombin, ADP,
and collagen needed to activate and
aggregate
• CPB activates plts- release of dense and
alpha granules
• Platelets adhere to exposed endothelium,
CPB circuit binding to fibrinogen
• Net result- Spent platelets or dysfunctional
platelets
Platelets
• Binding of Platelets to fibrin through the
GPIIb/IIIa can tear the receptor through
sheer forces
• Results in dysfunctional platelets
• Protease activated receptor (par-1) cleaved
• Use of Lysine or Kallekrien inhibitors
preserve Par-1 and preserve GP1b receptors
(decrease platelet activation)
Platelets
• Young platelets exhibit more robust
response to activation
• Older platelets less of a response
• CPB demonstrates older platelets
• Conclusion – set up post bypass platelet
dysfunction
CPB Stimulates Fibrinolysis
• Increase release of TPA with bypass due to
EC cell (animal models) stimulation
• Stimulus for TPA release XII, HMWK,
bradykinin, TF, thrombin
• 10-100 increase in plasmin production with
CPB
– Plasmin antiplatelet effects (platelet activation)
• Fibrin formation=> fibrin degradation
(result of cpb)
• Plasmin also cause platelet GPIb, GP
IIb/IIIa to internalize
Complement Activation
• Increase markers of complement activation
associated with increased perioperative
blood loss
• Administration of protamine induces
complement surge
• Complement also stimulates inflammatory
cascade, leukocytes, platelets, and ECs
Inflammatory Response
• Leukocytes bind and are activated by the
CPB tubing => TF
• Leukocytes and TF found in shed blood
• Decrease Protein C activation=> thrombin
formation
• Inflammatory response procoagulant
CPB effect on Coagulation
Monitoring anticoagulation
J Parmet
Team Leader
Cardiac Anesthesiology
Pennsylvania Hospital
Case Presentation
• 51 yr old male for coronary artery
revascularization
• h/o cocaine use and abuse
• h/o v fib arrest with successful resucitation
• Not cooled allowed to awake
• Neurologically intact, strange affect
Case presentation
• Smooth induction/ intubation/ invasive line
placement
• During swan patient require supplemental
muscle relaxation
• Continued high requirement for muscle
relaxation
• Difficulties ventilating Carbon dioxide
Case Presentation
• Propofol infusion started/ continued
increased muscle relaxation/ pt temperature
not decreasing
• Heparinized with 300 units/ kg => ACT
=380
• Do you want to initiate Cardiopulmonary
bypass?
Case Presentation
• Give another 10K heparin
• Want to initiate bypass?
• Repeat ACT after cooling?
Case presentation
•
•
•
•
•
•
Decided give 10K of heparin
Repeat ACT 340 sec
What now?
More Heparin?
Thaw FFP?
Cancel case? Get HIT work up? Measure
antithrombin III levels?
Questions?
•
•
•
•
What ACT for CPB?
Where does this number come from?
Why do we use the ACT?
Are there other options?
Monitoring Anticoagulation for CPB Effects of heparin? Or heparin levels ?
• PT- prothrombin time
• PTT- activated partial thromboplastin time
Prothrombin time
•
•
•
•
TF added tests factors- VII, X, V, II, I
TF + Factor => robust response
Vitamin K dependant factors (II,VII, IX , X)
Variability in thromboplastin potency
=>INR
• Excessive amounts of heparin will alter the
prothrombin time
Partial Thromboplastin time
• Thromboplastin + phospholipid (Cephalin
kaolin)
• TF absent
• Intrinsic pathway
• Not as robust a response (takes longer for
fibrin to form thrombus)
• Measure of Heparin effect- II, X, IX , XI
• One advantage to selecting the ACT to
monitor anticoagulation during cardiac
surgery is that other clotting time methods
(e.g., activated partial throm- boplastin
time, thrombin time) become either incoagulable (infinite) or highly variable at
heparin concentrations below those usually
required for safe CPB(10,13-15).
Thrombin Time
• Plasma + thrombin => fibrin (10 sec)
• Factors which affect
– Heparin
– Fibrinogen
– Fibrinogen degradation products
Activated clotting time
• Point of care test introduced by Casthely in
1966
• 1975 Bull – heparin monitoring protocol
ACT for cpb*
• 2 cc of whole blood withdrawn from arterial
circulation
• Mixed- with activator (celite or kaolin) in
test tube with magnet
• Tube 370c and rotates
• Clot holds magnet away from detector =>
end of test ( nl- 80-? sec)
Activated clotting time
• Celite
– More sensitive to heparin (higher ACT)
– More sensitive to hypothermia (higher ACT)
– Aprotinin artificially prolongs ACT
• Kaolin
– More resistant to heparin
– Not prolonged by aprotinin
– Binds aprotinin
Anticoagulation Protocols for
Cardiopulmonary Bypass
• How much Heparin should we give for
CPB?
• How do we know to give more heparin CPB
?
• Should we measure heparin effect or serum
concentration?
Factors affecting the Activated
Clotting Time
•
•
•
•
Heparin
Hypothermia
Hemodilution
Thrombocytopenia
– <20,000
– Severe Platelet inhibitors > 50%
– GP IIb/IIIa inhibitors alone no, with yes
• Protamine
– Gross protamine excess
Bull. Heparin therapy during
extracorporeal circulation. 1975 J Thor
Card Surg
Bull 1975 J thorac Card Surg
• Looked at 6 heparin dosing protocols
• Measured ACT’s
• Found a 3 fold patient variation with
heparin dosing
• Found in 4 of the dosing protocols ACTS
non therapeutic (<300)
• Defined therapeutic range 300< TR<600
Bull. 1975 J thorac Card surg
• Suggested ACT > 480 before initiating CPB
• Provide safety margin over an Act of 300
sec
• “ it appears many practitioners assume a
needed ACT > 480 for cpb and that number
represents minimum safe level ( not
scientifically validated)”
Case Presentation
• 48 yr old obese male for CABG
• Weight = 122 kg
• Calculated heparin dose= 36.6 K units
heparin
• ACT= 380
• What to do?
Case
•
•
•
•
•
•
•
Given 15 K of heparin
Repeat ACT = 410
Vein not ready patient temperature 35.3
Repeat ACT= 340
What to do?
How much heparin is to much?
Should we accept an ACT below 400 s?
Gravlee G. Variability of the activated
clotting time. Anesth Analg 1988:,67
469-72
•
•
•
•
•
46 pts undergoing CPB
Duplicate act
Baseline, 5 min post hep, 5 min post prot
Beef lung heparin- 300 unit/kg
Protamine administered by protamine
titration test
Variability Activated clotting
time
Gravlee and Rogers Anesth & analg 1988
Variability of ACT. A&A 1988
Variability of ACT. A&A 1988
ACT variability
• Once prolonged beyond 300 seconds, one
should not expect ACT to produce pinpoint
accuracy in determining heparin or protamine doses.
• Maintaining ACT values over 400
seconds during CPB probably constitutes
safe anticoagulation.
Metz and Keats. Low activated coagulation
time during cpb does not increase bleeding. J
thorac & Cardiovasc surg 1990
• 193 patients
• Heparin single dose 300 units /kg (porcine)
• Random ACT measurement, and heparin
levels
• Measured clot in CPB circuit chest tube
drainage
• Protamine reversal 1.5 mg/100 units of
heparin
Metz. J thorac Cardiovasc surg 1990
Metz Annal Thorac Surg
Metz. 1990
• Ave pump time = 59 min
• 51 patients Act < 400 , 4 <300
• Patients with low ACT values not bleed
more than those with higher values
• Heparin level decreased markedly during
CPB (2-4 u/ml) did not correlate with ACT
• Conclusion: No need to measure ACT for 1
hour of CPB
J thoracic Cardio 1990
• Gravlee- found maintaining higher CPB
heparin concentrations better suppressed
plasma coagulation but predisposed to
increased postoperative blood loss
• Measure fibrinopeptide a
Studies
• Gravlee. Variability of the activated
coagulation time. A&A
• Metz. . Low activated coagulation time
during cpb does not increase bleeding. J
thorac & Cardiovasc surg 1990
• Gravlee. Heparin Management protocol
for CPB influences heparin rebound but
not bleeding.Anesthesiology 1992
Studies
• Increased accuracy and precision of heparin
and protamine dosing reduces blood loss
and transfusion patients undergoing primary
cardiac operations. Jobes 1995
• Heparin and protamine titration do not
improve hemostasis in cardiac surgical
patients Can Journal 1998 Shore lesserson
Studies
• The Impact of heparin concentration and
activated clotting time monitoring on blood
conservation. Despotis J thorac Surgery
1995
•
•
•
•
Gravlee. Heparin Management protocol for
CPB influences heparin rebound but not
bleeding. Anesthesiology 1992
63 patients
Randomized- 200 units/kg bovine heparin,
additional heparin to achieve ACT > 400
sec (Group A) N=30
Or 400 units/kg to maintain heparin level of
> 4 units/ml (group H) N=33
Both groups same protamine neutralization
protocol
Heparin Management protocols for
cardiopulmonary bypass influences heparin
rebound but not bleeding
• Heparin dose group A 28,000
– Prot 193
• Heparin dose group H 57,000 (prot 256)
• 8 and 24 post no difference in chest tube
drainage
• Group H > incidence in hep rebound, rx
aggressive
• Antithrombin III levels lower in group H
• Small dose vs large dose no diff in blood
Gravlee. Heparin protocols
Solid line= Group A
Dotted line= Group H
Increased accuracy and precision of heparin
and protamine dosing reduces blood loss and
transfusion in patients undergoing primary
cardiac operations. Jobes 1995
• N= 52
• Control group (24)- heparin 300 units/kg
(porcine)- protamine 1 mg/100 units of
heparin (pump heparin not included)
• Test group(22)- heparin dose = 3(480ACT)/ (HRT-ACT) X EBV
– Protamine 0.02(ACT status-ACTbase)/
(ACTstatus-PRT) X EBV
Jobes. J thoracic Ccardiovasc 1995
Jobes. 1995
Heparin and protamine titration do not improve
hemostasis in cardiac surgical patients Can Journal
1998 Shore Lesserson
• 4 groups-
Results
Results
Why the difference?
• Initial heparin dose by Jobes not reported
• Transfusion triggers by Jobes not reported
nor standardized by protocol
• Different protamine management strategies
between the 2 groups
• No mention of the duration of
cardiopulmonry bypass
The Impact of heparin concentration and
activated clotting time monitoring on blood
conservation. Despotis J thoracic Surgery
1995
• N= 254
• Control= heparin (porcine) 250 units/kg
additional 5k to achieve ACT > 480s.
– Protamine 0.8 mg/100 units heparin
• Hepcon ACT= protamine titration method
– Additional heparin if ACT< 480s
– Protamine dose based on heparin concentration
Despotis et al
Despotis et al
ACT and Heparin concentrations
Despotis Results
Conclusions
• Patient variability exists with respect to
ACT response when given heparin
• Empiric 300 units per kg appears as
common practice in cardiac operating
rooms
• Achieving ACT >400 sec for CPB is
acceptable
Conclusions
• Studies investigating heparin concentration
vary in conclusions
• Differences in methodology as well as
duration of CPB remain important
• Lack of standardization for transfusion of
PRBC and of blood products may also
contribute to different conclusions reached
Conclusions
• A discordance exists between ACT measure
and serum heparin concentrations
• This discordance may contribute
microvascular bleeding 2ndary to using to
high a protamine reversal
• This discordance is exacerbating as the
duration of CPB increases
References
• Anticoagulation Monitoring during cardiac
surgery. Anesthesiology 1999 91:1122-51
• Gravlee. Cardiopulmonary bypass
principles and practice. Anticogulation for
cardiopulmonary bypass
• Heparin sensitivity and Resistance:
Management during cardiopulmonary
bypass. Anesth Analg 2013:116:1210-22
Heparin Pharmacology
• Polysaccharide contained in mast cells
– Acid, negative charge
• Unfractionated (beef lung vs porcine
mucosa)
– low molecular weight
– high molecular weight (1k-50K da)
• High molecular weight attraction for anti
thrombin III-thrombin complex- heparin
cofactor II
• Low molecular weight (< 6K) heparin bind
preferentially factor X no effect on anti
thrombin III
Thrombin inhibition -simultaneous binding of
heparin antithrombin III and thrombin
Must contain critical pentasaccharide sequence/ length 18oligosaccharide
Other affects of Heparin on
coagulation
• Heparin may induce fibrinolysis => activate
tissue plasminogen activator also releases
TFPI
• Heparin affects platelet function
–
–
–
–
Suppresses alpha granule release
Increase platelet factor - 4 release
Gp IIb / IIIa
Gp Ib/ IIa
Heparin
• Only 1 in 3 heparins have critical sequence
to bind to the antithrombin III complex
• Heparin also produces release of tissue
factor pathway inhibitor and affects the
extrinsic coagulation system (high dose)
• Possible initiation of the fibrinolytic
pathway
Heparin dosing
Bolus 2 mg/ kg heparin ( Bull )- heparin
response test
150 units / kg – 400 units / kg
- 150 u/kg for heparin bound circuit
- 200 u/kg with additional bolus
- 300 u/kg
Measure an ACT if > 300 s , if > 400 s, if >
480s
Heparin Pharmicokinetics
• Elimination half life varies with heparin
dose (50 % eliminated by renal excretion)
– 100 units => 60 min
– 400 units => 150 min
• Substantial variability in heparin
anticoagulant responsiveness- wide range of
heparin dose response (patient specific)
Heparin Resistance
• Despite adequate dosing of heparin the
ACT does not increase to the prescribed
institutional value to initiate (safely)
cardiopulmonary bypass
• The presumptive mechanism is
Antithrombin III deficiency (possible VIII)
• Acquired liver disease, malnutrition,
nephrotic syndrome, and heparin infusions
• Decrease antithrombin III levels
Heparin resistance
• The incidence of heparin resistance is
higher in patients with low anti-thrombin III
levels.
• ? Supplementation with AT III fails to
increase the ACT to target levels in all
patients (some other mechanism)
• Heparin anti III complex cleared by the
reticuloendothelial system
• Nicholson=> no diference in AT III levels
• Heparin responsiveness is measured by
ACT and just may be decreased in
patients receiving preop heparin
infusions
• Heparin resistance may be
demonstrated by a decrease
responsiveness in the ACT
Anticoagulation in patients undergoing
cardiac surgery on heparin infusions. Anesth
Analg 2000
• Patients receiving heparin H (n= 33) vs
patients not receiving heparin REF (n=32)
• Measured ACT and high dose thrombin
time
• ACT values increased less in the H group
• HiTT values did not differ between groups
• Thrombin/antithrombin III complex and
fibrin monomer not differ
Heparin Resistance
• > 600 units /kg with ACT no increase > 400
sec.
– Case reports as large as 1200 units/kg
– Larger doses associated with increased heparin
rebound
• RX–
–
–
–
More heparin
FFP
Antithrombin III concentrate
Accept lower ACT
Use of FFP
• Using FFP to prolong the ACT is based
upon case reports
• 2 units of FFP increase AT III levels to 500
iu
• Aviden demonstrated 2 units FFP not
increase heparin responsiveness in majority
of patients
Anti thrombin III concentrate
• No study demonstrate a reduction in
bleeding
• Anti thrombin III concentrate increases the
ACT in heparin resistant patients
• 500 iu-1000 iu
Scenarios
Conclusions
• HMW vs LMW anti thrombin III
complexes Factor X vs II
• Dosing affects elimination half life
• Hep resistance rxed with FFP no scientific
basis
• Hep resistance rxed with antithrombin III
concentrate expensive but effective
• Accepting lower target ACT may be most
effective
Heparin Neutralization
•
•
•
•
•
•
Protamine Pharmacology
Assessing Reversal of Anticoagulation
Protamine reactions
Protamine allergy
Who at risk for protamine allergy
Site of Administration
Protamine Pharmacology
Blood conservation strategy
• Increase preoperative hemoglobin
• Implement Acute normovolumic
hemodilution
• Reduce pump prime (mini CPB circuits)
• Administer Antifibrinolytics
– Lysine analogues- Amicar or Tranexamic Acid
• Discontinue preop P2Y12 inhibitors
– Plavix, effexor
The impact of blood conservation of
cardiac surgery: Is it safe and effective.
Ann Thorac surg 2010;90:451-9
• Englewood Hospital 2000-2004
• Blood conservation program
–
–
–
–
Permissive anemia Hgb < 6g/dl
Acute normovolemic hemodilution
Sug technique
antifibrinolytics
• New jersey department heath and senior
services registry (32,000 CABG patients)
• 586 Englewood Hospital (EH) CABG
• 586 Other hospital (OH) case matched
• 10% of EH vs 46% OH received blood
transfusion
• 5 EH vs 15 OH deaths p= .03
• Complications ( Stroke, Myocardial
infarction, multisystem organ failure,
prolonged ventilation,
Conclusion
• Permissive anemia can be tolerated for
cardiac surgical procedures
• Blood conservation program reduces the
incidence of Red blood cell transfusion
• By reducing Red blood cell transfusion
reduce patient mortality and morbidity
Blood Conservation
•
•
•
•
Acute normovolemic hemodilution
Antifibrinolytics
Retrograde Autologous Priming
Decrease prime in CPB mini- circuit
– Reduced diameter of CPB tubing
Acute normovolemic
hemodilution
• From large bore central catheter remove 250-500
cc whole blood
– Can use a-line
• Remove prior to heparinization
• Replace volume 1:1 with colloid (5 % salt pure
albumin)
• Reinfuse after CPB, after protamine
administration
Perioperative blood transfusion and blood
conservation in cardiac surgery: The Society of
thoracic surgeons and the society of cardiovascular
anesthesiologists practice guideline series
• “Acute normovolemic hemodilution is not
unreasonable for blood conservation but its
usefulness is not well established.”
Acute Normovolemic Hemodilution
• Contraindications
– Hemoglobin < 12 gm / dl or hematocrit < 36%
– Ejection fraction < 30%
– Creatinine > 2 mg/dl
Acute normovolemic
Hemodilution
• From large bore central catheter remove 250-500
cc whole blood
– Can use a-line
• Remove prior to heparinization
• Replace volume 1:1 with colloid (25 % salt pure
albumin)
• Reinfuse after CPB, after protamine
administration
Perioperative blood transfusion and blood
conservation in cardiac surgery: The Society of
thoracic surgeons and the society of cardiovascular
anesthesiologists practice guideline series
“Acute normovolemic hemodilution is not
unreasonable for blood conservation but its
usefulness is not well established.”
Administration of Antifibrinolytic
• Synthetic lysine analogues - Amino-caproic
acid
• Bolus, 150 mg/kg
• Infusion, 10 mg/kg/hr
• Continue 4-6 hours post CPB
Aprotinin administration associated with increased perioperative
mortality
Perioperative blood transfusion and blood
conservation in cardiac surgery: The Society of
thoracic surgeons and the society of cardiovascular
anesthesiologists practice guideline series
• Lysine analogues limit total blood loss and
the number of patients who require blood
transfusion after cardiac procedures. These
agents are slightly less potent blood-sparing
drugs compared with aprotinin but may
have a more favorable safety profile
Acute normovolemic
Hemodilution
• Contraindications
– Hemoglobin < 12 gm / dl or hematocrit < 36%
– Ejection fraction < 30%
– Creatinine > 2 mg/dl
Heparin Administration
• 300 units /kg of bovine heparin
– After IMA dissection
• 400 units/ kg if on heparin infusion
• Targeted Activated clotting time > 400 sec
• Activated clotting times > 480 sec may be
associated with less postoperative bleeding
Cardiopulmonary Bypass
• Maintain muscle relaxation
• Maintain volatile agent
– 1 MAC volatile agent
• Maintain mean arterial pressure
– MAP > 60 mmHg
• Maintain amnesia
• Maintain ACT > 400 seconds if using
aprotinin need ACT > 480 seconds
Cardiopulmonary bypass
• Single clamp technique
– Decrease incidence neuro injury
•
•
•
•
•
Distal anastomosis
Proximal anastomosis
Cardioplegia q 15 min
Assess electrical activity
Open IMA decrease MAP
– Minimize reperfusion injury
Cardiopulmonary bypass
Maintain tight blood glucose control (< 180)
Maintain hemoglobin < 6-7 gms/ dl
Maintain hematocrit > 18 %
* some recommend Hct > 22%
* use cerebral oximetry guide treatment
Attempt to avoid transfusion
Separation from bypass
• Resume full mechanical ventilation
– Reinflate lungs place on ventilator
• Achieve target heart rate 90 bpm
– Atropine, isoproterenol, Beta-dose epi
– Epicardial pacing ( AOO, DOO, DDD)
• Achieve target temperature
– Bladder > 340 C, Esophageal > 370 C
– When leave OR target temp > 350 C
• Maintain hemoglobin > 7 gm/dl
– Reinfuse whole blood removed after protamine
• Maintain K+ > 4 but < 5.5
Emergence Bypass
• Determine cardiac function
– Calculate cardiac index
– Transesophageal echocardiogram
• Administer Vasoactive agents
– If Cardiac Index < 2.0 or echo demonstrates poor
ventricular function
• Reversal of Heparin
– Protamine Sulfate 250 mg
– Act return to baseline
– Protamine not benign
• 4 types reactions
Post bypass
• Maintain fast track protocol
– Target extubation 4- 8 hours after emergence from CPB
• Maintain cardiac function
– Continue inotropes
• Maintain muscle relaxation
– Readminister vecuronium
• Redose amnestic and analgesic
– Begin propofol (expensive, maintain volatile anesthetic)
– administer midaz or fentanyl
Problems post bypass
• Bleeding
–
–
–
–
Long bypass
Previous clopidorel
thrombin inhibitors, GP IIbIIIa inhibitors
other anticoagulants
• Poor cardiac function
– Epinephrine, milrinone, norepinephrine, vasopressin,
intra-aortic balloon pump, ventricular assist device
• Poor respiratory function
Affects of Inhalation agent of
ischemic myocardium
• Ischemic preconditioning
– Cath lab- inflate balloon for 5 min prior to
PTCA
– Result reduction in myocardial damage
– “ ischemic preconditioning”
• Inhalation agents exhibit myocardial
protection
– Activate same pathways as ischemic
preconditioning
Poor intraoperative blood glucose control is
associated with a worsened hospital outcome after
cardiac surgery in diabetic patients. Ouattara
Anesthesiology 2005;103:677-8
Which inhalation agents?
• Sevoflurane
• Isoflurane
• Desflurane
Coagulation Factors
• Bradykinin levels increase 10 fold with
CPB
• Elevated bradykinins induce secretion of
TPA
• 5 fold increase in TPA levels
• 10-100 increase in plasmin generation with
CPB
• Fibrin consumption occurs during cpb
• Contact activation
• XII, XI, bradykinin, HMWK and
prekallikrein- rapidly degraded by kinins
• XII auto-cleaves itself when in contact with
the CPB circuit
• XII activates Kalllikreins which feedbacks
and cleaves XII
• Binds to the circuit
Platelet Cascade
Platelets
Two Phase Model
Continuous insulin infusion reduces mortality in patients
with diabetes undergoing coronary artery bypass Anthony P.
Furnary, MDa,d, Guangqiang Gao, MDa, Gary L. Grunkemeier, PhDb,
YingXing Wu, MDb, Kathryn J. Zerr, MBAb, Stephen O. Bookin, MDc, H.
Storm Floten, MDa,d, Albert Starr, MDa,d
• Staged trial 1st- subcutaneous administration
of insulin- 2nd stage insulin infusion
• Glucose levels- 150- 200- then 125-175
then 100-150
CPB upsets Coagulation balance
• CPB circuit is foreign surface
– Activates coagulation cascade and
inflammatory response (leukocytes host
attacks)
– Platelet activation and coat the CPB circuit
– First pass decreases antithrombin III levels
• Paralysis of the coagulation cascade by
heparin • hemodilution
• Hypothermia
Heparin
• Heparin binds to circulating antithrombin
and causes a conformational change that
accelerates its binding to and inactivation of
three critical coagulation factors:
• Thrombin, Xa, and IXa
• Heparin also has both direct and indirect
antiplatelet effects
• heparin binds to vWf at a site critical for
binding to platelet GPIb
End result
• Prothrombin => thrombin
• Fibrinogen cleaved to fibrin
– Basic structure of clot