Does BICARBONATE Correct Coagulation Function impaired by Acidosis in Swine ?

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Does BICARBONATE Correct Coagulation Function
impaired by Acidosis in Swine ?

• The Journal of TRAUMA injury, infection and
  Critical Care
• Wenjun S. Martini, Ph D, Michael A. Dubick, PhD
  
• ACCEPTED FOR PUBLICATION FEB 8,2006
• PRESENTOR 8901157 INT ???

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Abstract

• RESULT
• Reduced
• fibrinogen
• Platelet counts
• Thrombin generation
• clotting rapidity and MA
• Prolonged
• PT and PTT
• After pH neutralization, no reversal

Objective The effects of acidosis and
bicarbonate neutralization on coagulation function
were investigated in vivo.
CONCLUSION coagulopathy induced by acidosis
cant be reversed

• METHODS
• 12 pigs by infusing 0.2 mol/L HCl to pH 7.1.
• LR to maintain a pH of 7.1 (A-LR, n 6)
• or 0.3 mol/L bicarbonate to a pH of 7.4 (A-Bi, n
  6).
• 15 min after A-bi bicarbonate neutralization.
• Coagulation function was assessed
• by PT, PTT, thrombin generation,initial clot
  formation time (R),
• clotting rapidity (a), and clot strength(MA).

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Introduction ---why do this experiment ?

• Acidosis in trauma patients
• High mortality
• Due to tissue hypoxia from massive hemorrhage and
  massive transfusion of stored blood.?Disruption
  in coagulation (PT PTT prolonged)
• Study ISS (Injury Severity Scores)30 with 58
  massively transfused patient? 58 coagulopathy,
  if hypothermia low SBP(lt70mmHg) ?98

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• Acidosis in trauma patients
• Cause of disruption in coagulation
• Hypothermia (reported)? hypothermia reversal may
  correct hypothermia associated coagulation
  defects.
• Thrombin
• detrimental effects of acidosis and hypothermia
  on thrombin generation kinetics in a swine model.
• How about correct with pH neutralization??

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Injury Severity Score

• The Injury Severity Score (ISS) is an anatomical
  scoring system that provides an overall score for
  patients with multiple injuries. Each injury is
  assigned an Abbreviated Injury Scale (AIS) score
  and is allocated to one of six body regions
  (Head, Face, Chest, Abdomen, Extremities
  (including Pelvis), External). Only the highest
  AIS score in each body region is used. The 3 most
  severely injured body regions have their score
  squared and added together to produce the ISS
  score.
• The ISS score takes values from 0 to 75. If an
  injury is assigned an AIS of 6 (unsurvivable
  injury), the ISS score is automatically assigned
  to 75. The ISS score is virtually the only
  anatomical scoring system in use and correlates
  slinearly with mortality, morbidity, hospital
  stay and other measures of severity.

Region InjuryDescription AIS SquareTop Three
Head Neck Cerebral Contusion 3 9
Face No Injury 0  
Chest Flail Chest 4 16
Abdomen Minor Contusion of LiverComplex Rupture Spleen 2 5  25
Extremity Fractured femur 3  
External No Injury 0  
Injury Severity Score   Injury Severity Score   Injury Severity Score   50
 
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• The Abbreviated Injury Scale (AIS) is an
  anatomical scoring system first introduced in
  1969. Since this time it has been revised and
  updated against survival so that it now provides
  a reasonably accurrate was of ranking the
  severity of injury. The latest incarnation of the
  AIS score is the 1990 revision. The AIS is
  monitored by a scaling committee of the
  Association for the Advancement of Automotive
  Medicine.
• Injuries are ranked on a scale of 1 to 6, with 1
  being minor, 5 severe and 6 an unsurvivable
  injury. This represents the 'threat to life'
  associated with an injury and is not meant to
  represent a comprehensive measure of severity.
  The AIS is not an injury scale, in that the
  difference between AIS1 and AIS2 is not the same
  as that between AIS4 and AIS5. There are many
  similarities between the AIS scale and the Organ
  Injury Scales of the American Association for the
  Surgery of Trauma.

AIS Score Injury
1 Minor
2 Moderate
3 Serious
4 Severe
5 Critical
6 Unsurvivable
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Materials and Methods

• Protocol

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Materials and Methods 1

• Materials
• 12 crossbred Yorkshire swine
• 33 kg /- 1 kg
• Overnight fast
• Preaneshetized with glycopyrrolate (0.1 mg/kg)
  and Telazol (6 mg/kg)
• Induced with 5 isoflurane in 100 oxygen and
  maintained 13 isoflurane after intubation
• Right femoral artery and the right external
  jugular vein were cannulated for blood sampling
  and fluid infusion
• Arterial BT BP HR PH by XXXbrand

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Materials and Methods 2

• Induce metabolic acidosis
• 0.2 mol/L HCL in LR solution
• 0.07 mL/KG/min for initial 60ml solution
• followed by increase to 0.14 mL/kg/min to reach
  pH 7.3,
• then 0.21 mL/kg/min to reach pH 7.25,
• then 0.28 mL/kg/min to reach pH 7.1
• Divide 2 group
• A-Bi infusion of sodium bicarbonate at the rate
  of 0.28 mL/kg/min to neutralize arterial pH to
  7.4. after 15 min with stable PH

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Materials and Methods 3

• Minimize coagulation effects from shear-induced
  platelet activation
• 25mm single use catheter made from Tygon tubing
• Withdrawn from the catheter and the first 3 mL of
  blood withdrawn
• Hct, Platelet count, blood chemistry, PT, PTT,
  ACT by XXXbrand

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Materials and Methods 4

• Statistical analysis
• Mixed model ANOVA with SAS statistical
• Approved by the Institutional Animal Care and Use
  Committee
• Guide for the Care and Use of Laboratory Animals,
  National Research Council, 1996

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Results

• HR, MAP, BE, Hct ? no significant change in
  acidosis induction
• pH, Na, K, CA, Cl-, HCO3-
• Coagulation Profile
• Fibrinogen,
• platelet,
• PT, PTT, ACT,
• clotting rapidity, clot strength
• thrombin generation

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23534 min
15 min after stabilized
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Conclusion -1

• Infusion 0.2N HCL solution over nearly a 4 hr
  period
• 35 depletion in fibrinogen concentration
• 50 decrease in platelet count
• 50 inhibition in thrombin generation
• Blood clotting time was prolonged and clot
  formation and strength were impaired

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Conclusion -2

• Lack of improvement while Infusion of bicarbonate
  neutralized pH to 7.4
• Based on previous observations drug or
  resuscitation fluid may not be sufficient to
  restore normal coagulation function.
• Specific clotting factor replacement may be
  necessary for the ultimate reversal of impaired
  coagulation associated with acidosis

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Disscussion - OUTLINE

• Possible mechanisms of coagulopathy in acidosis
• PT, PTT, Thrombin time, fibrinogen, total protein
  (albumin and fibrinogen)
• Comparison with other studies
• Lactic acid vs hydrochloric acid
• Hemodilutional effects

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Disscussion possible mechanism-1

• 35 depletion in fibrinogen concentration
• Infusion 0.2N HCL solution over nearly a 4 hr
  period
• Degradation or inhibit?
• 2-4 fibrinogen synthesis rate per hr (in swine)?
  degradation, irreversible
• Without intervention, 10 hr for endogenous
  synthesis to replenish fibrinogen availability to
  normalize coagulation folowing acidosis even if
  there were no degradation

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• Total protein was only decreased about 10 - 15
  during the infusion
• Fibrinogen MW340,000 primarily confined in
  vascular pool, precursor in the coagulation
  process, T1/2 34 day
• Albumin MW 65,000 50 in vascular pool,,
  T1/216-18 days. Only 10 decrease in albumin
  concentration.
• ? different protein different vulnerable level??

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• 35 depletion in fibrinogen concentration?
  significant degradation
• Prospective study of 202 major torso trauma pt
  Mckinley et al..
• Coagulopathy remained uncorrected throughout a 24
  hr ICU period
• Possible need for fibrinogen supplementation

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Disscussion possible mechanism-2

• 50 decrease in platelet count
• Unable to explain, further studies is needed
• 50 inhibition in thrombin generation
• Acidosis depleted some coagulation substrates and
  inhibiting the thrombin generation burst
• Bicarbonate prevented the return of normal
  thrombin generation
• PT, PTT prolong
• Unable to define specific sites due to too many
  enzymes , factors and cofactors

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Disscussion Comparison with other studies

• Coagulation bicarbonate administration
• Wong et al.
• Bicarbonate increased from 12 mEq/L blood to 37
  mEq/L
• Thrombin time increased by 20
• In acidotic patients(n4), a 50 to 100
  prolongation in PT and PTT occurred.
• Our report shows that bicarbonate interferes with
  fibrin monomer assembly into fibrin polymer and
  inhibits thrombin production.
• ?MATCH!

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Disscussion Lactic acid vs hydrochloric acid

• Life threatening acidosis ?lactate
• hemolysis and high mortality

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Disscussion Hemodilutional effects

• 1st portion infusing 1.5L of 0.2N HCL in LR for
  4 hrs
• no changes observed in fibrinogen concentration,
  platelet counts and coagulation function in the
  group
• 2nd Portion A-Bi 0.9 L of bicarbonate was
  infusing
• Did not cause significant changes in plasma total
  protein, albumin and fibrinogen levels
• PT, PTT??
• Present study
• At least 50 is required before a significant
  change in clotting parameters is observed
• Estimate 10 - 15 in this hemodilution effect

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Thanks for your attention ?

• 8901157???