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Anesthesia and newer anticoagulants

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									 Anesthesia and newer anticoagulants
Dr.AL.Meenakshi sundaram MD DA
Prof of Anesthesiology, Thanjavur Medical College




                        GC Member, ISA National
                        State Secretary, ISA, TamilNadu
                 Why special?

• Increased awareness of DVT

• Increased prophylaxis

• Increased use of anticoagulants

• Increased surgical patients with anticoagulants
Types of Anticoagulants

• UNFRACTIONATED HEPARIN
• LMWH

• WARFARIN
• ANTIPLATELET AGENTS

• THROMBOLYTICS
• FIBRINOLYTICS
On /for Thrombolytic therapy
•  At risk of serious hemorrhagic events, particularly those who
  have undergone an invasive procedure.
• Second Consensus Conference on Neuraxial Anesthesia and
  Anticoagulation (April 25-28, 2002)

• Queries prior to the thrombolytic therapy
       Recent history of lumbar puncture
       Spinal or epidural anesthesia
       Epidural steroid injection

• Allow appropriate monitoring
On /for Thrombolytic therapy

• Evaluate whether fibrinolytic or thrombolytic drugs have
  been used preoperatively
• Any likelihood of being used intraoperatively or
  postoperatively

• Spinal or epidural anesthetic only in highly unusual
  circumstances
• Data are not available to clearly outline the length of time
  neuraxial puncture should be avoided after discontinuation of
  these drugs
    On /for Thrombolytic therapy
•      If neuraxial blocks at or near the time of fibrinolytic and
    thrombolytic therapy, neurological monitoring should be
    continued for an appropriate interval
•      Interval of monitoring should not be more than two hours
    between neurologic checks
•        Epidural catheter infusion should be limited to drugs
    minimizing sensory and motor block
•        There is no definitive recommendation for removal of
    neuraxial catheters in patients who unexpectedly receive
    fibrinolytic and thrombolytic therapy during a neuraxial
    catheter infusion
•        The measurement of fibrinogen level (one of the last
    clotting factors to recover) may be helpful
Anesthetic Management --Unfractionated Heparin
 Established over two decades ago

• Supported by in-depth reviews of case series & spinal hematoma
                               and the ASA Closed Claims Project

• Subcutaneous (mini-dose) prophylaxis – no contraindication

•The risk of neuraxial bleeding reduced by delay of the heparin inj


•increased in debilitated patients after prolonged therapy.

• platelet count assessed prior to neuraxial block and catheter removal
• (More than 4 days of Heparin Therapy– HITS)
Combining neuraxial techniques with intraoperative heparin


1.Avoid the technique in patients with other coagulopathies


2.Heparin to be delayed for 1 hour after needle placement


3.Indwelling neuraxial catheters should be removed 2-4 hours after
the last heparin dose and the patient's coagulation status is evaluated


4.Re-heparinization should occur one hour after catheter removal
Combining neuraxial techniques with intraoperative
heparin

5.Monitor the patient postoperatively to provide early detection
      of motor blockade


6.use of minimal concentration of local anesthetics -- early
       detection of a spinal hematoma


7.There are no data to support mandatory cancellation of a case in
      a bloody tap
   Preoperative LMWH

Can be assumed to have altered coagulation

Needle placement should occur at least 10-12 hours after the LMWH

Patients receiving higher (treatment) doses of LMWH, such as
enoxaparin 1 mg/kg every 12 hours, enoxaparin 1.5 mg/kg daily,
dalteparin 120 U/kg every 12 hours, dalteparin 200 U/kg daily, or
tinzaparin 175 U/kg daily will require delays of at least 24 hours to
assure normal hemostasis at the time of needle insertion

Neuraxial techniques should be avoided in patients with LMWH two
hours preoperatively ( peak anticoagulant activity)
   Postoperative LMWH
Twice daily dosing
Increased risk of spinal hematoma
The first dose of LMWH should be administered no earlier than 24
hours postoperatively (surgical) hemostasis

Indwelling catheters should be removed prior to initiation of LMWH
thromboprophylaxis

 If a continuous technique is selected, the epidural catheter may be
left indwelling overnight and removed the following day, with the
first dose of LMWH administered at least two hours after catheter
removal
Postoperative LMWH

Single daily dosing
This dosing regimen approximates the European application
The first postoperative LMWH dose should be administered 6-8
hours postoperatively

The second postoperative dose should occur no sooner than 24
hours after the first dose
Indwelling neuraxial catheters may be safely maintained

The catheter should be removed a minimum of 10-12 hours after
the last dose of LMWH
Subsequent LMWH dosing should occur a minimum of 2 hours
after catheter removal
Regional Anesthetic Management of the Patient on Oral
Anticoagulants

Perioperative warfarin--- controversial

The anticoagulant must be stopped, (ideally 4-5 days prior to the planned
procedure) and the PT/INR measured prior to initiation of neuraxial block.

Early after discontinuation of warfarin therapy, the PT/INR reflect
predominantly factor VII levels, and in spite of acceptable factor VII levels,
factors II and X levels may not be adequate for normal hemostasis.

Adequate levels of II, VII, IX, and X may not be present until the PT/INR is
within normal limits

The concurrent use of medications that affect other components of the clotting
mechanisms may increase the risk of bleeding complications without
influencing the PT/INR(Aspirin, NSAIDs, ticlopidine and clopidogrel,
unfractionated heparin and LMWH
Management of the Patient on Oral Anticoagulants
       Warfarin prior to surgery, (first dose was given more than
24 hours earlier) the PT/INR should be checked prior to neuraxial
block

       Low dose warfarin therapy during epidural analgesia --
PT/INR monitored on a daily basis, and checked before catheter
removal, if initial doses of warfarin are administered more than 36
hours preoperatively

       5 mg of warfarin –safe epidural analgesia . Higher dose
warfarin may require more intensive monitoring of the coagulation
status

       Neuraxial catheters should be removed when the INR is <1.5.
This value was derived from studies correlating hemostasis with
clotting factor activity levels greater than 40%.
Warfarin

       Neurologic testing of sensory and motor function should be
performed routinely during epidural analgesia for patients on
warfarin therapy



       An INR > 3 should prompt the physician to withhold or
reduce the warfarin dose in patients with indwelling neuraxial
catheters
Anesthetic Management of the Patient Receiving Antiplatelet
Medications
      Antiplatelet medications, including NSAIDs, thienopyridine
derivatives (ticlopidine and clopidogrel) and platelet GP IIb/IIIa
antagonists (abciximab, eptifibatide, tirofiban) exert diverse effects
on platelet function

    There is no wholly accepted test, including the bleeding time,
which will guide antiplatelet therapy

      History of easy bruisability/excessive bleeding, female
gender, and increased age

       The actual risk of spinal hematoma with ticlopidine and
clopidogrel and the GP IIb/IIIa antagonists is unknown

       Discontinuation of thienopyridine therapy and neuraxial
blockade is 14 days for ticlopidine and 7 days for clopidogrel
       Platelet GP IIb/IIIa inhibitors exert a profound effect
on platelet aggregation
       Following administration, the time to normal platelet
aggregation is 24-48 hours for abciximab and 4-8 hours for
eptifibatide and tirofiban

       Neuraxial techniques should be avoided until platelet
function has recovered.
       GP IIb/IIIa antagonists are contraindicated within four
weeks of surgery

       Cyclooxygenase-2 inhibitors have minimal effect on
platelet function and should be considered in patients who
require anti-inflammatory therapy in the presence of
anticoagulation
New Anticoagulants (Direct Thrombin Inhibitors and Fondaparinux)

New antithrombotic drugs which target various steps in the
hemostatic system
      inhibiting platelet aggregation
      blocking coagulation factors
      enhancing fibrinolysis are continually under development.


The most extensively studied are antagonists of specific platelet
receptors and direct thrombin inhibitors


Many agents have prolonged half-lives and are difficult to reverse
without administration of blood components
Thrombin Inhibitors

       Recombinant hirudin derivatives, including desirudin,
lepirudin, and bivalirudin inhibit both free and clot-bound thrombin.


        Argatroban, an L-arginine derivative, has a similar mechanism
of action


       Due to the lack of information available, no statement
regarding risk assessment and patient management can be made
Fondaparinux
Antithrombotic effect through factor Xa inhibition.

The FDA released it with a black box warning similar to that of the
LMWHs

The actual risk of spinal hematoma with fondaparinux is unknown

Close monitoring of the surgical literature
Until further clinical experience is available, performance of
neuraxial techniques should occur under conditions utilized in
clinical trials (single needle pass, atraumatic needle placement,
avoidance of indwelling neuraxial catheters)

If this is not feasible, an alternate method of prophylaxis should be
considered
NSAID


NSAIDs appear to represent no added significant risk

At this time, there do not seem to be specific concerns as to the
timing of single-shot or catheter techniques in relationship to the
dosing of NSAIDs, postoperative monitoring, or the timing of
neuraxial catheter removal.
           WHY THE CONCERNS…….
• TRYBA ETAL,
  INCIDENCE OF OF SPINAL HEMATOMA IS LESS THAN 1 IN 1,50000
  FOR EPIDURALS; 1 IN 220000 FOR SPINAL ANESTHETICS
• VANDER MUELLEN ETAL,ANESTH ANALG 1994;79;1165-77
  REVIEW OF LITERATURE BETWEEN 1906 AND 1994 REVEALED 42
  SPINAL HEMATOMAS ASSOCIATED WITH NEURAXIAL BLOCKADE
• AMERICAN HEART ASSOCIATION TASK FORCE ON MANAGEMENT OF
  PATIENTS WITH MI RECOMMENDS
      ASPIRIN/CLOPIDOGREL
      UNFRACTIONATED HEPARIN/LMWH
      GP IIb-IIIa ANTAGONIST
SIXTH AMERICAN COLLEGE OF CHEST PHYSICIANS
         CONSENSUS CONFERENCE
                CASE 1
• 80 YR OLD FEMALE POSTED FOR ELECTIVE TOTAL KNEE
  ARTHROPLASTY.PAST H/O AF, CCF AND HEMORRHAGIC
  GASTRITIS FOLLOWING ASPIRIN INGESTION.
• CURRENTLY ON CLOPIDOGREL,FRUSEMIDE, VERAPAMIL,
  AND LANZOPERAZOLE
• COAGULATION SCREEN NORMAL.
• DALTEPARIN SC GIVEN 10 HRS BEFORE THE ELECTIVE
  SURGERY TO PREVENT DVT.

• CONCERNS???????
• LACK OF MONITORING DEVICE FOR ANTI X a
  ACTIVITY
• PROLONGED HALF LIFE

• IRREVERSIBILITY WITH PROTAMINE
• PROLONGED IN RENAL FAILURE

• REVIEW OF LITERATURE
  40 CASES OF SPINAL HEMATOMA REPORTED IN
  U.S.A AFTER 5YRS OF USE OF LMWH
  13 CASES OF SPINAL HEMATOMA REPORTED IN
  EUROPE AFTER 10 YRS OF USE OF LMWH
           WHY THIS DIFFERENCE????
• IT WAS A OD DOSING IN EUROPE WITH FIRST DOSE BEING
  ADMINISTERED 12H PREOPERATIVELY.
• IN U.S IT WAS A BD DOSING REGIME WITH FIRST DOSE
  ADMINISTERED IN IMMEDIATE POST OPERATIVE PERIOD.
• FDA ISSUED WARNINGS……….
• FIRST CONSENSUS CONFERENCE IN 1998
       RADICULAR PAIN WAS NOT THE PRESENTING SYMPTOM
       MORE THAN HALF OF PATIENTS DEVELOPED NEURO DEFICIT
       12H AFTER CATHETER REMOVAL
       MEDIAN TIME BETWEEN LMWH THERAPY AND NEURO
       DYSFUNCTION WAS 3 DAYS
       TIME FROM ONSET OF SYMPTOMS TO LAMINECTOMY WAS
       >24HRS
       LESS THAN 1/3 PATIENTS REPORTED FAIR RECOVERY
DOSING VARIABLES ASSOCIATED WITH SPINAL
              HEMATOMA

PATIENT FACTORS
  FEMALE GENDER
  INCREASED AGE
ANESTHETIC FACTORS
  TRAUMATIC NEEDLE/CATHETER PLACEMENT
  EPIDURALTECHNIQUE
INDWELLING CATHETER DURING LMWH ADMINISTRATION
  LMWH DOSING FACTORS
  IMMEDIATE PREOPERTIVE LMWH ADMINISTRATION
  EARLY POSTOPERATIVE LMWH ADMINISRATION
  CONCOMITANT ANTIPLATELET ADMINISTRATION
  BD LMWH ADMINISTRATION
                 CURRENT GUIDELINES
• TIME INTERVALS BETWEEN NEURAXIAL NEEDLE PLACEMENT AND
  LMWH ADMINISTRATION SHOULD BE MAINTAINED.
• ASK NURSING STAFF TO ADMINISTER LMWH AT A SPECIFIC TIME.

• OD DOSING PREFERRED TO BD REGIME.
• ANTI Xa MONITORING NOT MANDATORY; IT DOES NOT PREDICT
  THE RISK OF BLEEDING.

• PRESENCE OF BLOOD DURING NEEDLE AND CATHETER PLACEMENT
  DOES NOT NECISSATE POSTPONEMENT.
• BUT INITIATION OF LMWH SHOULD BE DELAYED FOR 24 HRS
  POSTOPERATIVE.
• 10 HRS LATER THE PATIENT WAS GIVEN A CSE.
• EPIDURAL CATHETER CONTINUED FOR POSTOPERATIVE ANALGESIA
• PATIENT C/O PAIN OVER THE OPERATIVE SITE AND HER BACK
  FOLLOWING WHICH THE INFUSION RATE WAS INCREASED.
• THROMBOPROPHYLAXIS RESUMED- OD REGIME

• PHYSIOTHERAPIST NOTED NUMBNESS IN THE NON OPERATED LEG
  THE NEXT DAY WHICH SHE ATTRIBUTED TO THE EPIDURAL.
• 3RD POD THE EPIDURAL CATHETER WAS REMOVED, 12 HRS AFTER
  DALTEPARIN
• 5 HRS AFTER REMOVAL, THE NUMBNESS WAS PRESENT WITH MILD
  MOTOR WEAKNESS, ATTRIBUTED TO RESIDUAL EPIDURAL BLOCK.
• NEURO OPINION SOUGHT 48 HRS LATER AND A MRI OF SPINE WAS
  DONE.
                          CASE 2
• 55 yr old gentleman, h/o unstable angina, currently
  admitted to the coronary care unit. he is started on
  aspirin, atenelol,ntg and heparin iv. bypass grafting is
  planned and patient is interested in postoperative
  epidural pain relief

• Concerns??????
     Preoperative heparin
     Intraoperative heparin
     Postoperative heparin
                     PREOPERATIVE HEPARIN
• SC low dose heparin
       5000 u sc q 12 h for prevention of DVT
       No detectable changes in a pTT

• 9 published series over 9000 patients have had no complications
• Three surveys of opinions of anesthesiologists in UK, Denmark and
  Newzealand appear to feel that SC heparin should not be a
  contraindication for neuraxial blockade

Heparin to be delayed till 2 hrs after blockade
Heparin > 4 days platelet count to be assessed prior to neuraxial block
  or catheter removal
                    PREOPERATIVE IV HEPARIN
• Ideally neuraxial block 1-2 hrs before iv heparin.
• In the presence of traumatic attempt- incidence of spinal hematoma
  is 50 %.
• Cancellation of the surgery?????
• Risk of spinal hematoma


Ho etal, chest;2000,117, 551-55
  Complex mathematical analysis for the probability of spinal
  hematoma– 1:1528 for epidural;1:3610 for spinal

The authors hypothesised that this is an acceptable risk compared
  mortality of post op myocardial infarction
      INTRAOPERATIVE AND POSTOPERATIVE HEPARIN
• HEPARIN TO BE AVOIDED FOR 1 HR AFTER NEEDLE PLACEMENT
• CATHETERS REMOVED 2-4 HRS AFTER LAST HEPARIN; PATIENTS
  COAGULATION STATUS EVALUATED,RE HEPARINISATION STARTED 1
  HR LATER
• MONITOR PATIENT POSTOPERATIVELY FOR MOTOR BLOCK
• BLOODY TAP- DISCUSS WITH SURGEON THE RISK BENEFIT ANALYSIS.
                               CASE 3
• 60 yr old lady with parkinsonism, dementia and AF, posted for THR.
  She is currently on warfarin, anti parkinsonian drugs. INR was 2.1.
  Given vit K injection. INR dropped to 1.7.

• Concerns????

• Warfarin inhibits vit K dependent factors.

• But the effects of warfarin not apparent until a significant amount of
  biologically inactive factors are present.

• Dependent on factor half life…….
                      WHAT IT MEANS……………..
• 40% activity of Factor II, VII, IX, X is adequate for normal
  hemostasis

• INR AND PTT are most sensitive to changes in FAC X AND VII , its
  relative insensitive to FAC II activity.

• INR = 1.2 When FAC VII ACTIVITY IS 55%; INR =1.5 When FAC VII
  ACTIVITY IS 40%.

• Other problems with warfarin
      Narrow therapeutic range
      Enhanced response in old age, females, pre existing medical
  conditions[low wt, renal, cardiac, liver disease]
                            GUIDELINES
On discontinuation of warfarin,
  Factor VII activity will rapidly rise, so inr will decrease.
  Factor II AND X activities recover much more slowly; so hemostasis
  may not be adequate till then

In emergency- inject VIT K, USE FFP
Warfarin ideally stopped 4-5 days prior
PTT/INR Done Prior To Block

For those where warfarin is started for DVT,[low dose 5 mg]
 DO INR / PT IF a] DOSE GIVEN 24 HRS PRIOR
                  B] MORE THAN 1 DOSE GIVEN
                  C] EPIDURAL CATHETER IN SITU
                      CONTD…..

• REMOVE CATHETER ONCE INR <1.5

• NEURO TESING FOR SENSORY AND MOTOR FUNCTION AFTER
  REMOVAL OF CATHETER.

• INR>3 , WITHHOLD WARFARIN IF THERE IS AN INDWELLING
  CATHETER.
                CASE 4
• 58 YR OLD MAN WITH H/O MULTIPLE TIAs,
  HYPERTENSION, POSTED FOR LAPAROTOMY.
  HE IS ON ATENELOL, ASPIRIN AND
  CLOPIDOGREL

• CONCERNS??????
               ANTIPLATELET MEDICATIONS
• Aspirin in low doses [60-325 mg/day] inhibits platelet COX

• In higher doses 1.5 to2 g/day inhibits prostacyclin production[platelet
  aggregation inhibitor]

• Other NSAIDs- (Naproxen, Piroxicam, Ibuprofen) have antiplatelet
  activity , which normalises in 3 days.

• Thienopyridine derivatives- clopidogrel and ticlopidine which inhibit
  ADP induced platelet aggregation.

• Platelet GPIIB-IIIA receptor antagonists- Abciximab,
  Eptifibatide,tirofiban.
                    HOW TO MANAGE……..
• No wholly accepted test which will guide antiplatelet
  therapy. Thromboelastogram has been proposed to
  monitor clopidogrel therapy

• NSAIDS add no significant risk for spinal hematoma. So
  use of NSAIDs alone is not a risk for contraindication for
  neuraxial block.

• For thienopyridines
  Stop clopidogrel 7 days prior; ticlopidine 14 days prior

• GPIIB-IIIA RECEPTOR BLOCKERS
 Time for normal platelet aggregation after a single dose- 24
  –48 hrs after abciximab; 4-8 hrs after eptifibatide and
  tirofiban
        PLEXUS AND PERIPHERAL BLOCKS
• All cases of major bleeding after non neuraxial techniques
  occurred after psoas compartment or lumbar sympathetic
  block

• Case reports in literature with heparin, LMWH,
  thienopyridine derivatives

• Most have them had huge retroperitoneal hematomas ,
  with blood loss as great as 3 litre

• So significant blood loss rather than neural deficits are the
  major complications with drop in Hb, and hypotension.

• Treated with blood transfusion and conservative
  mangaement
I THOT A THOT, BUT THE THOT
I THOT WAS NEVER THE THOT
   I EVER THOT. SO I NEVER
  THOT THE THOT I THOT!!!!!
SUMMARY
                             Summary

       Consensus statements represent the collective experience of
recognized experts in the field of neuraxial anesthesia and
anticoagulation

      They are based on case reports, clinical series, pharmacology,
hematology, and risk factors for surgical bleeding

        An understanding of the complexity of this issue is essential
to patient management; a "cookbook" approach is not appropriate.

       Timing of catheter removal in a patient receiving
antithrombotic therapy should be made on an individual basis

       Weighing the small, though definite risk of spinal hematoma
with the benefits of regional anesthesia for a specific patient
       Coagulation status should be optimized at the time of spinal
or epidural needle/catheter placement, and the level of
anticoagulation must be carefully monitored during the period of
epidural catheterization

        Indwelling catheters should not be removed in the presence of
therapeutic anticoagulation, as this appears to significantly increase
the risk of spinal hematoma.

        Identification of risk factors and establishment of guidelines
will not completely eliminate the complication of spinal hematoma.

       Vigilance in monitoring is critical
There are two ways of meeting the difficulties


You alter the difficulties


You alter yourself to meet the difficulty

								
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