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張志偉 醫師 成功大學附設醫院骨科部主治醫師 成大醫學院骨科部臨床助理教授

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Presentation on theme: "張志偉 醫師 成功大學附設醫院骨科部主治醫師 成大醫學院骨科部臨床助理教授"— Presentation transcript:

1 張志偉 醫師 成功大學附設醫院骨科部主治醫師 成大醫學院骨科部臨床助理教授
南部地區藥事人員繼續教育 從藥物層面看人工膝關節置換手術後的照護 張志偉 醫師 成功大學附設醫院骨科部主治醫師 成大醫學院骨科部臨床助理教授

2 Osteoarthritis (OA) A common disease- progressive deterioration and loss of articular cartilage; subchondral sclerosis; osteophyte formation Radiographic knee OA in 1/3 > 60 y/o population (Framingham Osteoarthritis Study) Symptomatic OA in Taiwan- 5.8%; 1/3 OA involved the knee (1994 J Rheu).

3 非藥物性治療 Patient education Personalized social support
Weight loss (if overweight) Aerobic exercise programs & modification of activities of daily life Physical therapy Range-of-motion exercises Muscle-strengthening exercises Patellar taping Appropriate footwear- i.e lateral-wedged insoles、bracing Occupational therapy Assistive devices for ambulation、

4 藥物治療 Oral Acetaminophen
COX-2-specific inhibitor; Non-selective NSAID+ misoprostol or a PPI Non-acetylated salicylate Other pure analgesics: Tramadol Intraarticular - Opioids/ Glucocorticoids Viscosupplement- Hyaluronan (玻尿酸) Topical Capsaicin Methylsalicylate

5 若還不到要換關節的地步… 矯正切骨術 軟骨再生術 清創術 corrective osteotomy chondroplasty
debridement

6 李x柱 M 70, OA Knee, Right KSS: 39-> 85; FS: 25->80
Pre-op 0-90, Post-op 0-120

7 人工膝關節置換歷史沿革 In the 1860s, resection arthroplasty for arthritic knee (Fergusson); the first interposition arthroplasty using joint capsule (Verneuil) In the 1940s, the first artificial implants as molds fitted to the femoral condyles. In the 1950s, tibial replacement, but with loosening and persistent pain. In the 1950s, simple hinges combined femoral/ tibial articular surface replacements appeared- failed for the complex knee motion; high failure rates from aseptic loosening and postop infection. In 1971, Gunston‘s polycentric knee replacement had early success with its improved kinematics but failed with inadequate fixation to bone. In 1973, the Mayo Clinic introduced highly conforming and constrained Geomedic knee arthroplasty and a kinematic conflict arose. In 1973, the total condylar prosthesis by Insall, concentrated on mechanics and not try to reproduce normal knee motion. A rate of survivorship of 94% at 15 years’ follow-up (Ranawat, 1993). At the same time, a cruciate ligaments-retained prosthesis was developed. One theoretical way is with mobile tibial bearings

8 How to perform total knee arthroplasty ?

9 To now…… Most Commonly Performed Musculoskeletal-Related Procedures:
> 650,000 total knee arthroplasties (TKAs) are performed annually in U.S. to alleviate OA –related knee pain and disability.- AAOS [2011 Jul 24].

10 全人工膝關節置換的功能 The primary indication- to relieve pain from severe arthritis(減除疼痛). Significant and disabling pain. If knee dysfunction causing significant reduction in the patient's quality of life, this should be taken into account. Correction of significant deformity(矯正變形) is an important indication but is rarely used as the primary indication for surgery. Roentgenographic findings must correlate with a clear clinical impression of knee arthritis. Post-traumatic arthritis and limited function in youth or the elder (inherent longevity). Rarely, severe patellofemoral arthritis may justify arthroplasty because the expected outcome of arthroplasty is superior to patellectomy.

11 何時需要換人工膝關節? 疼痛厲害影響生活(Disabling Pain). 疼痛症狀無法以保守療法改善.
輔具,物理治療,藥物治療(止痛.消炎) 關節退化厲害無法矯正治療時. 健保規範: 70歲以下:2/3關節病變*,或1/3嚴重退化 70歲以上:1/3關節病變,保守治療3月無效 *關節病變;關節間隙小於二分之一以上

12 不適合開刀的病患(禁忌症) Absolute contraindications(絕對) • Knee sepsis
• A remote source of ongoing infection • Extensor mechanism dysfunction • Severe vascular disease • Recurvatum deformity secondary to muscular weakness • a well-functioning knee arthrodesis Relative contraindications: (相對) • Medical conditions precluding safe anesthesia and demands of surgery and rehabilitation. 身體狀況 • Skin conditions within the field of surgery (eg, psoriasis) • Prior knee osteomyelitis 難以控制的感染 • Neuropathic joint 神經造成關節病變 • Obesity

13 Expectations & Convalescence thereafter
The results of a TKA are often excellent. It relieves pain in over 90% of patients, and most need no assistance walking after recovery. Most prostheses last 10~15 years before loosening and requiring revision. Most patients require a short stay (3-5 days) in hospital to become safely independent of daily activities. Walking and ROM exercises will be started immediately. It may be necessary to use crutches or a walker for a few weeks or even months. The total recovery varies from 2-3 months to a year. Continue physical therapy after home until the strength and motion return. Avoid contact sports, but low impact activities, like swimming and golf, are usually possible after full recovery.

14

15 術後照護(1) Vital signs monitoring4 出血Bleeding Hemovac drainage monitoring
Fluid and blood replacement Average blood loss: 400 – 1200 cc NO Hemovac 止痛Pain control Regular IM narcotics Patient Control Analgesics (PCA) Epidural anesthesia

16 術後照護(2) Joint Function Rehabilitation Muscle power 肌力
Q setting, Straight leg raising Range of Motion 活動範圍 Continuous passive movement (postop day 2) Active flexion, bed sliding Active extension, passive flexion

17 開車都不出車禍??

18 術中或術後可能併發症 - be divided into 3 categories: • Complications specific to op proc.- blood loss; fracture; embolism • General peri-operative complications (including anesthesia) –infection, DVT, pain, stiffness • Other medical complications (post-op complications)

19 3 strategies to improve TKR delivery:
Multi-speciality pre-surgery evaluation of TKR candidates and in-patient management teams including anesthesia, internal medicine, & orthopedic surgery; dedicated OR teams in which TKR surgeons work with the same group of specialized arthroplasty scrub technicians and nurses; and involving patients in discharge planning before admission to better manage patient expectations. A Collaborative Of Leading Health Systems Finds Wide Variations In Total Knee Replacement Delivery And Takes Steps To Improve Value (Health Affairs, May 9) by Ivan M. Tomek, MD,

20 Infection 感染 Infection after total hip and knee replacement is a real concern since it can be fatal, though it is a rare occurrence (0.3~1.9%) 1~ 2 % of primary procedure; 3~ 4 % of revisions.

21 Radiographic findings
Similar to findings in loosening with progressive interface widening; no definitive radiographic signs to differentiate except soft tissue gas Soft tissue gas (ulcer or sinus tract) Laminated periosteal reaction (rare) Diagnostic evaluation Blood tests; Aspiration; Nuclear medicine Treatment Acute e.g. after dental surgery Open surgical lavage Subacute or chronic Resection of hardware with flail hip (Girdlestone) Resection of hardware and placement of cement spacer

22 Recommendations for Prophylactic Antibiotics in Specific Surgery
Procedure Likely pathogen Recommended antibiotics Alternative Duration Total hip arthroplasty S. aureus CoNS Cefazolin 1 gm iv then 1 gm q8h ivd Vancomycin 1 gm ivd < 2 days Total knee arthroplasty Cefazolin 1 gm then 1 gm q8h ivd Internal fixation for close reduction < 1 day Spine Other selective, non-prosthesis bone procedures Administer weight-based combined antibiotics (cephalosporin and vancomycin) at least 30 minutes prior to surgical incision J Microbiol Immunol Infect 2004;37:71-74.

23 When To Discontinue Prophylactic Antibiotics
be discontinued within 24 hours after the end of the operation (O) Pre-blended antibiotic bone cements (?) continuing antimicrobial agents until all catheters and drains (X)

24 J Bone Joint Surg Am. 2006;88:

25 預防勝於治療 !! Considering the common pathogens from remote site (oral hygiene) or neighboring (UTI, URI)

26 Pain control 定義- 一種實質,或潛在組織傷害或與此傷害相關的不快感和情緒體驗
"Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". International Association for the Study of Pain, 1986 26

27 不爽?!

28 Response to General Stress
痛會惡化生理狀況 Response to General Stress Endocrine/ Metabolic  ACTH, cortisol, catecholamines, IL-1  insulin  H2O, Na+ retention 心跳 , 血壓 , 呼吸 , 血流  , 蠕動 ACTH = adrenocorticotropic hormone Kehlet H. Reg Anesth.1996;21(6S):35–37. Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.

29 痛會惡化心理狀況 惡性循環 Acute Pain Anxiety Sleep deprivation Depression
Cousins M, Power I. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed; 1999:447–491.

30 疼痛類型: 急性 vs 慢性 急性疼痛: 慢性疼痛: 持續時間少於1個月 傷後疼痛持續超過1個月 如果沒有妥善治療會演變為慢性疼痛
4/14/2017 疼痛類型: 急性 vs 慢性 急性疼痛: 持續時間少於1個月 如果沒有妥善治療會演變為慢性疼痛 慢性疼痛: 傷後疼痛持續超過1個月 反覆發作超過3個月 接續在組織受傷之後發生 Acute pain Chronic pain 持續時間Duration Hours/ weeks Months/ years 病因Pathophysiology Identified Rarely known 預後Prognosis Predictable Unpredictable 治療方式Treatment Anagelsics Multidiscipline Traditionally, pain has been defined as acute or chronic—that is, pain that lasts for a short time, or pain that continues or recurs for a longer period. But this division is not perfect. Acute pain can become chronic if left untreated and chronic pain can have acute exacerbations or flare-ups.1,2 In recent years, a number of different schools of thought about the pain continuum have been emerging; these are focused on mechanism-based pain, rather than duration of pain. Investigators continue to study the relationship between the severity of acute, postoperative pain and the development of chronic pain A current concept of pain centers around neuronal plasticity. Neurons detecting and transmitting pain display plasticity (the capacity to change function, chemical profile or structure, which contributes to altered sensitivity to pain). There are 3 forms of neuronal plasticity: activation (rapid onset), modulation (follows repeated, intense stimuli), and modification (follows prolonged, intense stimuli or nerve damage)3 References: 1. Beers MH, Berkow R, eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck & Co., Inc.; 1999: Cousins M, Power I. Acute and postoperative pain. In: Wall PD, Melzack R, eds. Textbook of Pain. 4th ed. Edinburgh, UK: Churchill Livingstone; 1999: Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288: 1Beers MH, Berkow R, eds. The Merck Manual. 17th ed.; 1999: Cousins M et al. Textbook of Pain. 1999: 30 30

31 治療急性疼痛的目標與策略 及時介入與適當調整藥物,以充分控制疼痛。 達到可接受的疼痛程度。 協助病人從原本的疾病或受傷恢復。
“Acute and chronic pain have nothing in common but the four letter word ‘pain’.” John D. Loeser, Univ. of Washington, Seattle, US “Persistent pain should be considered a disease state of the nervous system, not merely a prolonged acute pain symptom of some other disease conditions.” Basbaum AI . PNAS 1999; 96:

32 非藥物治療 藥物治療 被視為是對藥物治療的補充治療措施;心理干預、針灸、電刺激和物理治療都可能有效對某些急性疼痛有幫助。
可使用的藥物包括鴉片類藥物、非類固醇抗炎藥和局部麻醉劑,及輔助藥物如抗鬱劑、抗癲癇藥和細胞膜穩定劑等。 為獲得最好療效與同時最小副作用,許多止痛藥物要小心調整與客制化(individualization)的劑量投與。 多模鎮痛-同時使用不同類鎮痛藥,增加治療急性疼痛效果。

33 Acute pain after TKA Multimodal analgesia-多模止痛One or more methods to control pain Pre- emptive analgesia- an anti-nociceptive treatment using one or more analgesics prior to an event to prevent sensitization or limit post-injury pain; Preop analgesia is thought more effective than an equal post-operative dose Local infiltration anesthesia 術中 Ice packing 術後 Patient control anesthesia 術後 Medication- parenteral narcotics still play a major role

34 對各種疼痛的治療選擇 對不同病患,沒有所謂單一最有效的治療藥物!! NSAIDs非類固醇抗發炎藥物 Nonselective
4/14/2017 對各種疼痛的治療選擇 NSAIDs非類固醇抗發炎藥物 Nonselective COX-2 selective Opioids 鴉片類止痛藥物 Local anesthesia 局部麻醉劑 Adjunctive therapy 輔助治療 Others 其他 對不同病患,沒有所謂單一最有效的治療藥物!! There are many ways to effectively treat acute and chronic pain. Each of these options offers its own benefits and risks. No single option is right for every patient. NOTE: for more information on treatment options, see: Kehlet H, Dahl JB. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg. 1993;77: 34 34

35 Gastroduodenal Mucosa
傳統 NSAID 作用機轉 Arachidonic Acid Traditional NSAIDs: { Cyclooxygenase Anti-inflammatory Analgesic Gastrointestinal Toxicity Renal Toxicity X Prostaglandins This is the original (1971) view of the arachidonic acid cascade. NSAID’s systemically inhibit prostaglandin production, causing beneficial analgesic and anti-inflammatory actions as well the G.I., renal and platelet adverse reactions. Within this understanding of the system, there does not appear to be any way to avoid the “double edged sword” effects of the NSAID’s. Support Renal and Platelet Function Inflammation and Pain Protect Gastroduodenal Mucosa

36 Milestones in NSAIDs Development
1899: Aspirin 1949: Steroid 1951: Phenylbutazone 1963: Indomethacin 1965: Ibuprofen 1966: Diclofenac 1968: Naproxen 1970: Piroxicam 1990’s: COX-2 inhibitors Milestones in NSAIDs Development From Aspirin to COX-2 * 1950: Acetaminophen

37 使用NSAIDs引發GI副作用之危險因子
Age >60 years History of ulcer disease Concomitant steroid use High-dose or multiple NSAIDs Concomitant anticoagulant use Scheiman JM Gastroenterol Clin North Am 1996; 25(2):

38 CONCERNS of NSAIDs GI 胃腸道 CV 心血管 Kidney 腎功能- hydration Others- Money?
>> Key point- 首先講求不傷身; 感冒藥使用觀念

39 Blood loss The blood loss in the TKR is from 1014 to ml (Kim et al JBJS-b). Average- 400~1200 ml Surgical trauma (soft tissue & bone cutting) induced Coagulation vs fibrinolysis

40 Peri-operative Blood Loss
Tourniquet ON for OP Tourniquet Release for hemostasis Hemovac for Drainage Intra-op blood loss Post-op Blood loss

41 Factors affecting blood loss after TKA
Patient age, sex, BMI, arterial blood pressure, preop Hb and Hb preceding transfusion, operation/ tourniquet time, blood loss and volume of blood transfused patients with hypertension and lower pre-op Hb level as well as longer duration of surgery.

42 Strategies to reduce blood loss in TKA
Reduce operation time surgeon’s experience, trained team Reduce surgical trauma less invasive approach, surgical method (guiding tech.) Fibrin tissue adhesive (containing clot-forming components) Transamine (tranexamic acid)- anti-fibrinolytic agent Intra-operative injection- Epinephrine+ xylocaine, bupivacaine Others? Anesthesia method

43

44 Vein thromboembolism 靜脈血栓
Migration Embolus Pulmonary embolism Pulmonary embolism (PE) and deep vein thrombosis (DVT) are referred to collectively as venous thromboembolism (VTE). There is a very strong association between pulmonary embolism (PE) and deep vein thrombosis (DVT):1 90% of pulmonary emboli are the results of DVT2 82% of patients with acute PE had detectable DVT at the time PE was diagnosed.1 Deep Vein Thrombosis Girard et al., Chest 1999

45 Clotting- a key event in multiple vascular disorders
Venous Pulmonary embolism (PE) Clot migrates to the lungs where it becomes trapped Most of the clots from DVT Arterial Stroke Atrial fibrillation (AF) can cause the development of clots, which can travel to the brain AF increases stroke risk ~5-fold Acute coronary syndromes (ACS) comprise unstable angina and MI – The underlying cause is clots Acute Coronary Syndrome Deep venous thrombosis (DVT) Clots are formed in the deep veins of the leg Risk factors include: Damage to blood vessel Stasis Too much clotting factors So, we can conclude that the ability of blood to clot is of course a very important natural property, without which we would not be able to survive. However, under certain conditions, blood may clot while still inside the blood vessel which is a serious, life threatening medical condition. Deep vein thrombosis (DVT), is a clot in the deep veins, usually in the legs. The blood clot may detach and lodge in another part of the blood circulatory system like blood vessels in the lungs and lead to a very serious, life-threatening condition called pulmonary embolism (PE). In patients with heart attack or with rhythm problems such as atrial fibrillation, small clots forming in the heart can cause further heart attacks or strokes if they float up to the brain. In acute coronary syndrome, including acute heart attack, a blood clot is the most common cause of a blocked coronary artery. All of these are serious complications.

46 Approx. 80% DVTs are clinically silent
VTE/PE is often clinically silent, difficult to diagnose, and DEADLY !! > 70% fatal PEs are only detected post mortem1 VTE/PE is often clinically silent and is diffiult to diagnose. Approx. 80% DVTs are clinically silent and silent PE occurs in more than 50% of patients with symptomatic proximal DVT. However, VTE/PE may be deadly! Approx. 80% DVTs are clinically silent 1. Goldhaber SZ et al. Am J Med. 982;73:822–826; 2. Sandler DA, et al. J Royal Soc Med. 1989;82:203–205

47 Virchow‘s Triad of Thrombogenesis
血液組成的變化 血流的變化 Activation of coagulation Immobilisation and congestion Three conditions can contribute to DVT: injury to the lining of the vein or impairment of endothelial anticlotting efftct; an increased tendency for blood to clot or too much clotting factors; and slowing of the blood flow in the veins, mostly due to imobilization and local congestion. Endothelial antithrombogenicity 血管結構的變化

48 Venous v.s. Aterial Thrombosis
Venous Thrombosis / AF Mechanism Major Low flow ( Stasis) Hypercoagulability Minor Vessel wall injury Clinical Features Large thrombi High levels of thrombi generation Prolong period of coagulation activation Arterial Thrombosis Mechanism Major High shear Endothelial injury Minor Hypercoagulability Clinical Features Smaller thrombi Less marked thrombi generation Shorter duration of coagulation activation

49 VTE risk factors in surgical patients
Level of risk Description Low Minor surgery in young patients (<40 years) with no additional risk factors Moderate Minor surgery in patients with additional risk factors Surgery in patients aged 40–60 years with no additional risk factors High aged >60 years, or 40–60 y/o with additional risk factors* Surgery in patients with multiple risk factors Total hip or knee replacement; hip fracture surgery Surgical patients are at high risk of VTE, although VTE often is not manifested until after discharge. As many as 10% of hospital deaths were attributed to PE in a retrospective study of surgical patients. Although high-risk groups of patients can be identified, it is not always possible to predict the probability of an individual developing clinically important VTE. Fatal PE commonly occurs without warning and diagnosis cannot made until after death. Geerts WH et al. Chest ;126:338S–400S Lindblad B et al. Br J Surg. 1991;78:849–852 *Additional risk factors: previous VTE, cancer, molecular hypercoagulability, obesity, hereditary thrombophilias, inflammation of infection and anaesthesia Geerts et al. Chest 2004; Lindblad et al. Br J Surg 1991

50 Epidemiology of VTE after orthopaedic surgery
Major lower limb surgery alone: a high VTE risk, irrespective of any additional risk factors Geerts et al. Chest 2008 TKA/ THA: Asymptomatic DVT- 40% to 60%; Proximal DVT- 15% to 25%; Fatal PE in 0.5% to 2%; Symptomatic and fatal PEs: THA> TKA. Hip fracture surgery, multiple trauma patients, esp pelvic or lower extremity frx DVT- 20% to 60% prior pelvic trauma. VTE without prophylaxis % DVT (range) % fatal PE (range) Elective hip replacement 42–57 0.1–2.0 TKR 41–85 0.1–1.7 Hip fracture 46–60 0.3–7.5

51 Exacerbated risk of VTE with primary or secondary hypercoagulable states
OKU9 Chap 12 **Several risk factors- hypercoagulable states, advanced age, prior history, immobility, smoking, obesity, stroke cancer.

52 VTE after Major Orthopaedic Surgery Continues to be a Risk After Discharge
Symptomatic VTE events reported in 1.5–10.0% within 3 months after surgery.1 Most events occur after discharge from hospital.1 Risk of symptomatic VTE after major orthopaedic surgery continues to be higher than that in the general population for at least 2 months after surgery.1 However, VTE is often clinically silent, and the first manifestation (which may be a fatal PE) often occurs after discharge from hospital.1,2 Primary prevention of VTE is recommended for all patients undergoing major orthopaedic surgery of the lower limbs1 1. Geerts WH et al. Chest 2004;126:338–400S. 2. Ferri F. Ferri’s Clinical Advisor 2004: 6th edn. St Louis: Mosby, 2003.

53 亞洲人與白種人在靜脈栓塞發生率上的種族差異….. 預期(Perception) 或 事實 (reality)?
China 3 centres Malaysia 1 centre Taiwan 4 centres S. Korea 5 centres Philippines 3 centres Thailand 1 centre Indonesia 2 centres 19 centers in 7 countries; 407 patients ( )

54 The primary goal of prophylaxis in VTE is to prevent symptomatic and fatal PE
Mechanical Prophylaxis Pharmacologic Prophylaxis Others Pneumatic Compression Boot & Plantar Compression Device

55 A Brief History of Anticoagulant Therapy
Convenience and clinical benefit Direct Xa inhibitors: Single target, oral Present Indirect Xa inhibitors: Dual target, parenteral 2000s 1990s DTIs: single target, oral and parenteral 1980s LMWHs: multiple targets, parenteral In summary, Very often, blood clots in the veins are formed silently and commonly after surgeries such as hip replacements or knee surgery. These silent, large clots can break away, float in the veins and then get lodged in the lungs causing what is called a pulmonary embolus, or PE for short, which is a serious, often fatal condition and is the commonest cause of sudden death after surgery. This life-threatening event could be prevented if we had the right treatment to stop the abnormal formation of blood clots, in the first place. Anticoagulants is the cornerstone of treatment and prevention of VTE. Convenient oral administration, improved specificity and direct mode of action have guided the development of anticoagulation since the discovery of heparin in the 1930s. Oral, direct Factor Xa inhibitors are part of this evolution, as they directly and specifically inhibit Factor Xa. Alban S. Eur J Clin Invest. 2005;35(Suppl 1):12. 1940s VKAs: multiple targets, oral 1930s UFH: multiple targets, parenteral DTIs, direct thrombin inhibitors Alban. Eur J Clin Invest 2005

56 New, predictable, oral anticoagulants are needed
傳統抗凝藥物 Vitamin K antagonists, e.g. warfarin (oral) 藥效不易預期 Onset慢;需 bridging therapy 需密切監控其international normalized ratio (INR)與劑量調整 增加出血風險 Heparin (injectable) 須皮下或連續輸注給藥;不利居家使用 須密切定期監測activated partial thromboplastin time與時常調整劑量 Heparin 誘發血小板減少症(HIT) LMWHs (injectable) 須皮下給藥; New, predictable, oral anticoagulants are needed

57 Conventional anticoagulant : Multi - target
II VII IX X + Proteins C and S Warfarin TF/VIIa IXa Indirectly LMWH IIa + Antithrombin III + Xa VIIIa XIa Fondaparinux + Xa XIIa Antithrombin III Emerging Single-target Xa IIa 传统的抗凝药物作用于凝血瀑布中的多个靶点: 华法林为维生素K拮抗剂。通过竞争性抑制维生素K环氧化物还原酶,致使体内还原型维生素K缺乏,使得有活性的凝血因子Ⅱ、Ⅶ 、Ⅸ 、X不能合成。华法林还能抑制具有抗凝作用的蛋白C和蛋白S的羧化作用,因而具有促凝作用,然而大部分情况下其抗凝作用占主导。 低分子量肝素(LMwH)是通过化学或酶学解聚的方法从普通肝素中衍生出来的片断,其长度约为普通肝素的三分之一。同普通肝素一样,LMWH通过增强抗凝血酶III(AT III)的活性来发挥抗凝效应。LMWH 的抗X a/抗II a活性比值在2:1~4:1之间;而普通肝素的抗X a/抗子II a比值约为1:1。 磺达肝癸钠是间接的Xa因子抑制剂,必须通过与抗凝血酶III结合后才能抑制Xa因子,所以称之为”间接Xa因子抑制剂。 新型的抗凝药物将朝向直接作用于凝血瀑布中单一关键点的方向发展,如Xa因子,因为,这样可能会带来一致的结果(使得药物既安全又有效)。 作用於Coagulation waterfall 單一關鍵點可產生可預測性之抗凝效果 57

58 新型的抗凝藥物 標的抗凝血劑,包括 Xa凝血因子抑制劑和凝血蛋白酶直接抑制劑(DTIs) Xa凝血因子抑制劑 凝血蛋白酶直接抑制劑
Fondaxparinux (Arixtra ®; GlaxoSmithKline)- injection Idraparinux - injection Rivaroxaban (Xarelto®; Bayer)- oral 凝血蛋白酶直接抑制劑 Hirudin (Lepirudin ®)- injection Bivalirudin (Angiomax ®; The Medicines Company)-injection Ximelagatran (Exanta®; Astra-Zeneca )- oral Dabigatran (Pradax®; Boehringer Ingelheim )

59 AMPLIFICATION / PROPAGATION PHASE
Factor Xa: Pivotal Point in the Coagulation Pathway Extrinsic pathway Intrinsic pathway INITIATION PHASE Tissue factor Factor Xa Phospholipids FVa–FXa Ca2+ Prothrombinase complex > 1: 1000 AMPLIFICATION / PROPAGATION PHASE Platelet aggregation Prothrombin Thrombin Fibrinogen Fibrin CLOT

60 ACCP guidelines for VTE prevention after major orthopaedic surgery
Eighth ACCP conference on antithrombotic therapy Procedure Recommendation Duration Grade Elective THR LMWH, fondaparinux, or adjusted-dose VKA At least 10 days and up to 35 days 1A Elective TKR 1A 2B ASA is not recommended as sole prophylaxis in any of these patients ACCP, American College of Chest Physicians; ASA, acetylsalicylic acid; LMWH, low molecular weight heparin; VKA, vitamin K antagonists Geerts et al. Chest 2008

61 Decade of Bone & Joint 2000-2010 公元兩千年.骨骼關節年
Arthritis 關節炎 M-S Trauma 創傷 Osteoporosis 骨疏鬆 Spinal disorders 背痛 Crippled children 小兒

62 Take home message 人工膝關節置換是目前最常施行的骨科手術之一,常用以治療嚴重膝關節病變
急性疼痛的控制在施行膝關節置換手術,不論術前或術後都相當重要 為避免可能術後感染,需自個人衛生習慣著手預防 為減少手術失血,抗凝藥物可於術前7至10天前開始停藥 對術後可能血栓形成,除早期活動外,尚可考慮藥物治療

63 Thank You

64 Brief test ( )人工膝關節置換是目前最常施行的骨科手術之一,常用以治療嚴重膝關節病變;台灣每年有近2萬例手術
( )在施行膝關節置換手術術前或術後,急性疼痛的控制都相當重要;目前多模止痛為主流 ( )為避免可能術後感染,需自個人衛生習慣著手預防;特別是口腔衛生與泌尿道清潔 ( )為減少手術失血,抗凝藥物可於術前7至10天前開始停藥 ( )所有的NSAID都有造成心血管風險,不宜長期使用


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