Dr.AL.Meenakshi sundaram MD DAProf of Anesthesiology, Thanjavur Medical College

GC Member, ISA NationalState Secretary, ISA, TamilNadu

Anesthesia and newer anticoagulants

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

• 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

On /for Thrombolytic therapy

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 dosingIncreased risk of spinal hematomaThe 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 dosingThis dosing regimen approximates the European applicationThe 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 doseIndwelling neuraxial catheters may be safely maintained

The catheter should be removed a minimum of 10-12 hours after the last dose of LMWHSubsequent 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%.

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

Warfarin

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

FondaparinuxAntithrombotic 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

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.

NSAID

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/CLOPIDOGRELUNFRACTIONATED HEPARIN/LMWHGP 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 LITERATURE40 CASES OF SPINAL HEMATOMA REPORTED IN U.S.A AFTER 5YRS OF USE OF LMWH13 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 SYMPTOMMORE THAN HALF OF PATIENTS DEVELOPED NEURO

DEFICIT 12H AFTER CATHETER REMOVALMEDIAN TIME BETWEEN LMWH THERAPY AND NEURO DYSFUNCTION WAS 3 DAYSTIME FROM ONSET OF SYMPTOMS TO LAMINECTOMY

WAS >24HRSLESS THAN 1/3 PATIENTS REPORTED FAIR RECOVERY

DOSING VARIABLES ASSOCIATED WITH SPINAL HEMATOMA

PATIENT FACTORSFEMALE GENDERINCREASED AGE

ANESTHETIC FACTORSTRAUMATIC NEEDLE/CATHETER PLACEMENTEPIDURALTECHNIQUE

INDWELLING CATHETER DURING LMWH ADMINISTRATIONLMWH DOSING FACTORSIMMEDIATE PREOPERTIVE LMWH ADMINISTRATIONEARLY POSTOPERATIVE LMWH ADMINISRATIONCONCOMITANT ANTIPLATELET ADMINISTRATIONBD 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 heparinIntraoperative heparinPostoperative 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 blockadeHeparin > 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, 551-55Complex 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 warfarinNarrow therapeutic rangeEnhanced response in old age, females, pre existing

medical conditions[low wt, renal, cardiac, liver disease]

GUIDELINESOn 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 FFPWarfarin ideally stopped 4-5 days priorPTT/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 thienopyridinesStop 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