Oral anticoagulants and regional anesthesia for joint replacement surgery Reported by R1 康庭瑞 2002/11/5.

Oral anticoagulants and Oral anticoagulants and regional anesthesia for joint regional anesthesia for joint

replacement surgeryreplacement surgery

Reported by R1 Reported by R1 康庭瑞康庭瑞2002/11/52002/11/5

Case present Case present

Identifying dataIdentifying data Name: Name: 王王 XX 傭傭 Age: 73 years oldAge: 73 years old Gender: maleGender: male Chart number: 2000625Chart number: 2000625 Bed number: 11B11-1Bed number: 11B11-1 Operative day: 2002.10.28Operative day: 2002.10.28

Brief historyBrief history

Chief complaint:Chief complaint: Right knee walking pain for more than 1 montRight knee walking pain for more than 1 mont

hh Present illness: Present illness: 1)1) Falling down and right knee was injured yearFalling down and right knee was injured year

s ago.s ago.2)2) Intermittent right knee pain and soreness, pIntermittent right knee pain and soreness, p

oor weight bearingoor weight bearing3)3) Severe varus deformity and osteoarthritis wiSevere varus deformity and osteoarthritis wi

th joint space narrowingth joint space narrowing

Brief historyBrief history

Past history:Past history:1)1) Heart disease with 3VD s/p CABG 2 years ago Heart disease with 3VD s/p CABG 2 years ago

at at 振興 振興 hospitalhospital2)2) Denied of DM, liver, renal, lung diseasesDenied of DM, liver, renal, lung diseases3)3) Drug and food allergy: deniedDrug and food allergy: denied4)4) Previous operation history: (1) CABG 2 years Previous operation history: (1) CABG 2 years

ago. (2) Gall bladder stone s/p. (3) Cataract s/ago. (2) Gall bladder stone s/p. (3) Cataract s/pp

5)5) Smoking (+)– 1~2 PPD, alcohol comsuSmoking (+)– 1~2 PPD, alcohol comsumption– deniedmption– denied

Brief historyBrief history

Current drugs:Current drugs:1)1) Bokey (Aspirin): 100Bokey (Aspirin): 100 ㎎㎎2)2) Lipitor (Atorvastatin)Lipitor (Atorvastatin)3)3) Mirobect (Atenolol) Mirobect (Atenolol) 4)4) Imdur (Isosorbride 5-mononitrate)Imdur (Isosorbride 5-mononitrate)5)5) Lasix, spironolactoneLasix, spironolactone6)6) Narcaricin (Benzbromarone)Narcaricin (Benzbromarone)

Brief historyBrief history Physical examinationPhysical examination1)1) Consciousness: clearConsciousness: clear2)2) Vital sign: T/P/R—36.5/60/15 BP—Vital sign: T/P/R—36.5/60/15 BP—

100/60100/60㎜㎜ HgHg3)3) BW:55.2BW:55.2㎏㎏ , BH: 152, BH: 152㎝㎝4)4) HEENT: conjunctiva—pink, JVE—nilHEENT: conjunctiva—pink, JVE—nil5)5) Chest: symmetric expansion, breathing Chest: symmetric expansion, breathing

sound—clearsound—clear6)6) Heart: NSR, no murmurHeart: NSR, no murmur7)7) Extremities: no pitting edemaExtremities: no pitting edema

Brief historyBrief history

Laboratory data: (20Laboratory data: (2002.10.27)02.10.27)

• Blood type: O, Rh(+)Blood type: O, Rh(+)• WBC: 6310WBC: 6310• RBC: 344RBC: 344• Hb: 11.1Hb: 11.1• PLT:205PLT:205• Bilirubin T: 0.31Bilirubin T: 0.31

• GOT: 16GOT: 16• BUN: 42.5BUN: 42.5• Creatinine: 2.34Creatinine: 2.34• Na: 139Na: 139• K: 4.89K: 4.89• Cl: 102Cl: 102• Sugar AC: 136Sugar AC: 136

Discussion Discussion

Regional anesthesia and anticoagulatioRegional anesthesia and anticoagulation– n– Journal of clinical anesthesiaJournal of clinical anesthesia, Februa, February 2001ry 2001

Update on spinal anesthesia– Update on spinal anesthesia– AnesthesiAnesthesiologyology, May 2001, May 2001

Spinal-epidural hematoma following epiSpinal-epidural hematoma following epidural anesthesia in the presence of antipdural anesthesia in the presence of antiplatelet and heparin therapy– latelet and heparin therapy– AnesthesiolAnesthesiologyogy, October 2001, October 2001

DiscussionDiscussion

Oral anticoagulants and regional Oral anticoagulants and regional anesthesia for joint– anesthesia for joint– regional regional anesthesia and pain medicineanesthesia and pain medicine, , January-February 2002January-February 2002

Epidural anesthesia prevents hyper-Epidural anesthesia prevents hyper-coagulation in patients undergoing coagulation in patients undergoing major orthopedic surgery– major orthopedic surgery– regional regional anesthesia and pain medicineanesthesia and pain medicine, May-, May-June 2002June 2002

The use of regional anesthesia and analgesia iThe use of regional anesthesia and analgesia in the presence of anticoagulation has always n the presence of anticoagulation has always been a controversial issuebeen a controversial issue

Incidence of spinal hematoma with spinal aneIncidence of spinal hematoma with spinal anesthesia without anticoagulation is estimated asthesia without anticoagulation is estimated at 1:220,000t 1:220,000small surveys, anecdotal reports, small surveys, anecdotal reports, and expert opinionand expert opinion

Anticoagulants used in the surgical population Anticoagulants used in the surgical population as prophylaxis and treatment for thrombotic cas prophylaxis and treatment for thrombotic conditionondition

Review of commonly used Review of commonly used anticoagulantsanticoagulants

Antiplatelet drugs– inhibit platelet functionAntiplatelet drugs– inhibit platelet function1)1) Aspirin(ASA): irreversible inactivates COX, evAspirin(ASA): irreversible inactivates COX, ev

en low-dose aspirin (40~81en low-dose aspirin (40~81 ㎎㎎ ) may suppress ) may suppress TXA2 synthesis & PLT aggregation, inhibiting TXA2 synthesis & PLT aggregation, inhibiting 1 hr after ingestion, entire lifespan 10 days≒1 hr after ingestion, entire lifespan 10 days≒

2)2) Newer generations: inhibiting ADP-induced PNewer generations: inhibiting ADP-induced PLT aggregation (entire lifespan) or PLT GPIIb/LT aggregation (entire lifespan) or PLT GPIIb/IIIa receptor (48 hrs)IIIa receptor (48 hrs)

3)3) NSAIDs: reversibly and competitively inhibit NSAIDs: reversibly and competitively inhibit COX, duration is dose-dependent and half-lifCOX, duration is dose-dependent and half-life of the NSAIDe of the NSAID

Review of commonly used anticoagReview of commonly used anticoagulantsulants

Oral anticoagulants (Warfarin)Oral anticoagulants (Warfarin) Interfering with the Vit. K-dependent coagulatiInterfering with the Vit. K-dependent coagulati

on protein, factors on protein, factors II II (thrombin), (thrombin), VIIVII, , IXIX, and , and XX Inhibiting Vit. K reductases, depletes Vit. KHInhibiting Vit. K reductases, depletes Vit. KH22, ,

and limits carboxylationand limits carboxylation PT and INR may not accurately measure true aPT and INR may not accurately measure true a

ntithrombotic activity ntithrombotic activity A decrease in factors A decrease in factors IIII and and XX (longer half-life) i (longer half-life) i

s more important for the antithrombotic efficas more important for the antithrombotic efficacy of warfarin cy of warfarin

Review of commonly used anticoagReview of commonly used anticoagulantsulants

HeparinHeparin Binding with antithrombin Binding with antithrombin IIIIII, which accelerates , which accelerates

inactivation of factors inactivation of factors IIII, , IXIX, , XX, , XIXI and and XIXI Mixture of polysaccharide chains, MW ranging frMixture of polysaccharide chains, MW ranging fr

om 5,000 to 30,000; the length of the heparin chaom 5,000 to 30,000; the length of the heparin chain determines which factor will be inhibitedin determines which factor will be inhibited

Extensive binding to plasma proteins complicateExtensive binding to plasma proteins complicated the pharmacokineyics of heparind the pharmacokineyics of heparin

Review of commonly used anticoagReview of commonly used anticoagulantsulants

LMWH has relatively greater anti-LMWH has relatively greater anti-XaXa acti activity, more predictable bioavailability anvity, more predictable bioavailability and longer half-lifed longer half-life

PTT doesn’t accurately reflect the degrPTT doesn’t accurately reflect the degree of anticoagulation, factor X levels donee of anticoagulation, factor X levels don’t correlated with potential for bleedin’t correlated with potential for bleedingg

Regional anesthesia and anticoagulRegional anesthesia and anticoagulantsants

Concurrent use of other anticoagulants increaConcurrent use of other anticoagulants increasing the risk of bleeding complication without sing the risk of bleeding complication without influencing standard laboratory testinfluencing standard laboratory test

Minimize the degree of sensory and motor defiMinimize the degree of sensory and motor deficit of the analgesic regimencit of the analgesic regimen

Epidural catheters should be removed at the nEpidural catheters should be removed at the nadir of anticoagulant therapyadir of anticoagulant therapy

Routine continued neurologic monitoring for aRoutine continued neurologic monitoring for at least 24 hourst least 24 hours

Regional anesthesia and antiplateleRegional anesthesia and antiplatelet medicationst medications

1,000 patients undergoing orthopedic procedu1,000 patients undergoing orthopedic procedures while taking anti-PLT drugs and 1,800 obstres while taking anti-PLT drugs and 1,800 obstetric patients with low-dose aspirin(60etric patients with low-dose aspirin(60 ㎎㎎ ) rec) received neuraxial anesthetic and no hematoma eived neuraxial anesthetic and no hematoma were notedwere noted

Review of all reported cases of neuraxial hemaReview of all reported cases of neuraxial hematoma from 1906 to 1994, only 4 of 61 cases wertoma from 1906 to 1994, only 4 of 61 cases were associated with the use of anti-PLT drugs, ane associated with the use of anti-PLT drugs, and 3 use of another anticoagulantd 3 use of another anticoagulant

A case reportA case report

63-yr-old woman(16563-yr-old woman(165 ㎝㎝ ;75;75 ㎏㎏ ), ASA class ), ASA class III, III, ffor reimplantation of a prosthesis of the right kor reimplantation of a prosthesis of the right kneenee

One subcutaneous injection of LMWH (nadropOne subcutaneous injection of LMWH (nadroparin,3800IU/day) as a prophylactic antithrombarin,3800IU/day) as a prophylactic antithrombotic treatment (12hrs before surgery)otic treatment (12hrs before surgery)

Pre-OP, PTT:33s(30~40s), PT:84% (70~120%), IPre-OP, PTT:33s(30~40s), PT:84% (70~120%), INR:1.01 (therapeutic level 2~4.5), PLT count:15NR:1.01 (therapeutic level 2~4.5), PLT count:151*109/L (150~400)1*109/L (150~400)

Epidural puncture and insertion of the catheteEpidural puncture and insertion of the catheter were uneventfulr were uneventful

Combined regional and general anesthesia waCombined regional and general anesthesia was induceds induced

At the end of surgery, continuous epidural infuAt the end of surgery, continuous epidural infusion of 0.25% marcaine (8ml/h) was initiated. sion of 0.25% marcaine (8ml/h) was initiated. LMWH was reestablished 6h after the end of suLMWH was reestablished 6h after the end of surgeryrgery

18hrs later, epidural infusion rate↑to 12ml/h 18hrs later, epidural infusion rate↑to 12ml/h and 2 boluses of 12ml marcaine given for surgiand 2 boluses of 12ml marcaine given for surgical and back paincal and back pain

400400 ㎎ ㎎ ibuprofen rectally for back painibuprofen rectally for back pain Painful during injection→remove catheter 7≒Painful during injection→remove catheter 7≒

h after 2h after 2ndnd post-OP LMWH given post-OP LMWH given

At that time, the coagulation parameters were At that time, the coagulation parameters were within normal range, PLT count was 118*10within normal range, PLT count was 118*1099/L/L

After removal, she received PCAAfter removal, she received PCA 10hrs after removal, back pain↑and voiding di10hrs after removal, back pain↑and voiding di

fficulty,↓muscle strength and sensation in botfficulty,↓muscle strength and sensation in both lower limbsh lower limbs

MRI revealed a spinal-epidural hematoma froMRI revealed a spinal-epidural hematoma from T10 to L4m T10 to L4

Emergency decompressive surgery→ partially Emergency decompressive surgery→ partially organized and freshorganized and fresh

No neoplastic changes or vascular malformatiNo neoplastic changes or vascular malformationsons

Specific drugs taken per-OP:500Specific drugs taken per-OP:500 ㎎ ㎎ QID ibuproQID ibuprofen on her own for arthritic pain and the last dfen on her own for arthritic pain and the last dose 10h before surgery≒ose 10h before surgery≒

High dose ibuprofen and a single doseHigh dose ibuprofen and a single dose Lower limit of normal range PLT count, and deLower limit of normal range PLT count, and de

creased after surgerycreased after surgery 2 subcutaneous injection of LMWH before cath2 subcutaneous injection of LMWH before cath

eter removaleter removal Back pain as an early symptom can be absent Back pain as an early symptom can be absent

with continuous epidural analgesia. Insufficienwith continuous epidural analgesia. Insufficient analgesia was probably the first clinical signt analgesia was probably the first clinical sign

German society of anesthesiology and intensivGerman society of anesthesiology and intensive care medicine: free interval of 1~2 days after e care medicine: free interval of 1~2 days after NSAID, and at least 3 days without ASA-contaiNSAID, and at least 3 days without ASA-containing medication for central neuraxial manipulning medication for central neuraxial manipulationation

Epidural anesthesia preventEpidural anesthesia prevents hyper-coagulation in paties hyper-coagulation in patients undergoing major orthonts undergoing major ortho

pedic surgerypedic surgery

methodsmethods

Clot signature analysis(CSA) to assess PLClot signature analysis(CSA) to assess PLT and clotting functionT and clotting function

Pre- and post-OP venous blood were colPre- and post-OP venous blood were collected from 41 P’t of major orthopedic lected from 41 P’t of major orthopedic surgery surgery