Download Anesthesia and newer anticoagulants

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
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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