domingo, 24 de octubre de 2010

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SISTEMA NERVIOSO FETAL

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PRECLAMPSIA

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ITU

MALFORMACIONES FETALES

NEUROSONGRAFIA

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LISTA DE LA ACOG

LIST OF TITLES — NOVEMBER 2010
Practice Bulletins provide obstetricians and gy ne col o gists with cur rent information on established tech niques and
clinical management guidelines. The American College of Obstetricians and Gynecologists (the College) con tin u ous ly
surveys the field for ad vanc es to be in cor po rat ed in these series and monitors existing bul letins to ensure they are current.
Individual bul le tins are with drawn from and added to the series on a continuing basis and reaffirmed periodically.
Open access to lists of titles, published monthly by the College, is available as follows:
Committee Opinions and Technology Assessments—www.acog.org/from_home/publications/green_journal/COListOfTitles.pdf
Practice Bulletins—www.acog.org/from_home/publications/green_journal/PBListOfTitles.pdf
Publication Reaffirmed
Number Title Date Date

Committee on Practice Bulletins—Obstetrics

4 Prevention of Rh D Alloimmunization (Obstet Gynecol Vol. 93, No. 5) May 1999 2009
6 Thrombocytopenia in Pregnancy (Obstet Gynecol Vol. 94, No. 3) September 1999 2009
9 Antepartum Fetal Surveillance (Obstet Gynecol Vol. 94, No. 4) October 1999 2009
12 Intrauterine Growth Restriction (Obstet Gynecol Vol. 95, No. 1) January 2000 2008
13 External Cephalic Version (Obstet Gynecol Vol. 95, No. 2) February 2000 2009
17 Operative Vaginal Delivery (Obstet Gynecol Vol. 95, No. 6) June 2000 2009
19 Thromboembolism in Pregnancy (Obstet Gynecol Vol. 96, No. 2) August 2000 2008
20 Perinatal Viral and Parasitic Infections (Obstet Gynecol Vol. 96, No. 3) September 2000 2009
22 Fetal Macrosomia (Obstet Gynecol Vol. 96, No. 5) November 2000 2009
29 Chronic Hypertension in Pregnancy (Obstet Gynecol 2001;98:177 –185) July 2001 2010
30 Gestational Diabetes (Obstet Gynecol 2001;98:525–538) September 2001 2010
31 Assessment of Risk Factors for Preterm Birth (Obstet Gynecol 2001;98:709–716) October 2001 2010
33 Diagnosis and Management of Preeclampsia and Eclampsia
(Obstet Gynecol 2002;99:159–167) January 2002 2010
36 Obstetric Analgesia and Anesthesia (Obstet Gynecol 2002;100:177–191) July 2002 2010
37 Thyroid Disease in Pregnancy (Obstet Gynecol 2002;100:387–396) August 2002 2008
38 Perinatal Care at the Threshold of Viability (Obstet Gynecol 2002;100:617–24) September 2002 2008
40 Shoulder Dystocia (Obstet Gynecol 2002;100:1045–50) November 2002 2008
43 Management of Preterm Labor (Obstet Gynecol 2003;101:1039–47) May 2003 2008
44 Neural Tube Defects (Obstet Gynecol 2003;102:203–13) July 2003 2008
48 Cervical Insufficiency (Obstet Gynecol 2003;102:1091–9) November 2003 2008
49 Dystocia and Augmentation of Labor (Obstet Gynecol 2003;102:1445–54) December 2003 2009
52 Nausea and Vomiting of Pregnancy (Obstet Gynecol 2004;103:803–15) April 2004 2009
55 Management of Postterm Pregnancy (Obstet Gynecol 2004;104:639–46) September 2004 2009
56 Multiple Gestation: Complicated Twin, Triplet, and High-Order
Multifetal Pregnancy (Joint with the Society for Maternal–Fetal Medicine)
(Obstet Gynecol 2004;104:869–83) October 2004 2009
60 Pregestational Diabetes Mellitus (Obstet Gynecol 2005;105:675–85) March 2005 2007
68 Antiphospholipid Syndrome (Obstet Gynecol 2005;106:1113 – 21) November 2005 2007
71 Episiotomy (Obstet Gynecol 2006;107:957–62) April 2006 2008
75 Management of Alloimmunization During Pregnancy
(Obstet Gynecol 2006;108:457–64) August 2006 2008
76 Postpartum Hemorrhage (Obstet Gynecol 2006;108:1039–47) October 2006 2008
77 Screening for Fetal Chromosomal Abnormalities (Joint with the
Committee on Genetics and the Society for Maternal–Fetal
Medicine) (Obstet Gynecol 2007;109:217–27) January 2007 2008
78 Hemoglobinopathies in Pregnancy (Obstet Gynecol 2007;109:229–37) January 2007 2008
80 Premature Rupture of Membranes (Obstet Gynecol 2007;109:1007–19) April 2007
82 Management of Herpes in Pregnancy (Obstet Gynecol 2007;109:1489–98) June 2007 2009
86 Viral Hepatitis in Pregnancy (Obstet Gynecol 2007;110:941–55) October 2007 2009
88 Invasive Prenatal Testing for Aneuploidy (Obstet Gynecol 2007;110:1459–67
(Joint with the Committee on Genetics) December 2007 2009
90 Asthma in Pregnancy (Obstet Gynecol 2008;111:457–64) February 2008 2009
92 Use of Psychiatric Medications During Pregnancy and Lactation
(Obstet Gynecol 2008;111:1001–20) April 2008 2009
95 Anemia in Pregnancy (Obstet Gynecol 2008;112:201–7) July 2008
97 Fetal Lung Maturity (Obstet Gynecol 2008;112:717–26) September 2008
100 Critical Care in Pregnancy (Obstet Gynecol 2009;113:443–50) February 2009
101 Ultrasonography in Pregnancy (Obstet Gynecol 2009;113:451–61) February 2009
102 Management of Stillbirth (Obstet Gynecol 2009;113:748–61) March 2009
105 Bariatric Surgery and Pregnancy (Obstet Gynecol 2009;113:1405–13) June 2009
106 Intrapartum Fetal Heart Rate Monitoring: Nomenclature, Interpretation,
and General Management Principles (Obstet Gynecol 2009;114:192–202) July 2009
107 Induction of Labor (Obstet Gynecol 2009;114:386–97) August 2009
113 Inherited Thrombophilias in Pregnancy (Obstet Gynecol 2010;116:212–22) July 2010
115 Vaginal Birth After Previous Cesarean Delivery (Obstet Gynecol 2010;116:450–63) August 2010
*116 Management of Intrapartum Fetal Heart Rate Tracings
(Obstet Gynecol 2010;116:1232–40) November 2010
251 Obstetric Aspects of Trauma Management (Obstet Gynecol Vol. 92, No. 3) September 1998 2006

Committee on Practice Bulletins—Gynecology

14 Management of Anovulatory Bleeding (Obstet Gynecol Vol. 95, No. 3) March 2000 2009
15 Premenstrual Syndrome (Obstet Gynecol Vol. 95, No. 4) April 2000 2010
28 Use of Botanicals for Management of Menopausal Symptoms
(Obstet Gynecol Vol. 97, No. 6) June 2001 2010
35 Diagnosis and Treatment of Cervical Carcinomas
(Obstet Gynecol 2002;99:855–867) May 2002 2010
39 Selective Estrogen Receptor Modulators (Obstet Gynecol 2002;100:835–44) October 2002 2008
42 Breast Cancer Screening (Obstet Gynecol 2003;101:821–32) April 2003 2006
46 Benefits and Risks of Sterilization (Obstet Gynecol 2003;102:647–58) September 2003 2008
Publication Reaffirmed
Number Title Date Date
2 Practice Bulletins List of Titles
Committee on Practice Bulletins—Gynecology (continued)
50 Osteoporosis (Obstet Gynecol 2004;103:203–16) January 2004 2008
51 Chronic Pelvic Pain (Obstet Gynecol 2004;103:589–605) March 2004 2008
53 Diagnosis and Treatment of Gestational Trophoblastic Disease
(Joint with the Society of Gynecologic Oncologists)
(Obstet Gynecol 2004;103:1365–77) June 2004 2008
57 Gynecologic Herpes Simplex Virus Infections
(Obstet Gynecol 2004;104:1111–7) November 2004 2006
59 Intrauterine Device (Obstet Gynecol 2005;105:223–32) January 2005 2009
61 Human Papillomavirus (Obstet Gynecol 2005;105:905–18) April 2005 2009
63 Urinary Incontinence in Women (Obstet Gynecol 2005;105:1533–45) June 2005 2009
65 Management of Endometrial Cancer
(Joint with the Society of Gynecologic Oncologists)
(Obstet Gynecol 2005;106:413 – 25) August 2005 2009
67 Medical Management of Abortion (Obstet Gynecol 2005;106:871–82) October 2005 2009
72 Vaginitis (Obstet Gynecol 2006;107:1195–1206) May 2006 2008
73 Use of Hormonal Contraception in Women With Coexisting Medical Conditions
(Obstet Gynecol 2006;107:1453–72) June 2006 2008
81 Endometrial Ablation (Obstet Gynecol 2007;109:1233–48) May 2007 2009
83 Management of Adnexal Masses (Obstet Gynecol 2007;110:201–14) July 2007 2009
84 Prevention of Deep Vein Thrombosis and Pulmonary Embolism
(Obstet Gynecol 2007;110:429–40) August 2007
85 Pelvic Organ Prolapse (Obstet Gynecol 2007;110:717–29) September 2007 2009
89 Elective and Risk-Reducing Salpingo-oophorectomy
(Obstet Gynecol 2008;111:231–41) January 2008 2010
91 Treatment of Urinary Tract Infections in Nonpregnant Women
(Obstet Gynecol 2008;111:785–94) March 2008 2010
93 Diagnosis and Management of Vulvar Skin Disorders
(Obstet Gynecol 2008;111:1243–53) May 2008
94 Medical Management of Ectopic Pregnancy (Obstet Gynecol 2008;111:1479–85) June 2008
96 Alternatives to Hysterectomy in the Management of Leiomyomas
(Obstet Gynecol 2008;112:387–400) August 2008
99 Management of Abnormal Cervical Cytology and Histology
(Obstet Gynecol 2008;112:1419–44) December 2008
103 Hereditary Breast and Ovarian Cancer Syndrome (Joint with the Commitee on Genetics
and the Society of Gynecologic Oncologists) (Obstet Gynecol 2009;113:957–66) April 2009
104 Antibiotic Prophylaxis for Gynecologic Procedures (Obstet Gynecol 2009;113:1180–9) May 2009
108 Polycystic Ovary Syndrome (Obstet Gynecol 2009;114:936–49) October 2009
109 Cervical Cytology Screening (Obstet Gynecol 2009;114:1409–20) December 2009
110 Noncontraceptive Uses of Hormonal Contraceptives January 2010
(Obstet Gynecol 2010;115:206–18)
112 Emergency Contraception (Obstet Gynecol 2010;115:1100–9) May 2010
114 Management of Endometriosis (Obstet Gynecol 2010;116:223–36) July 2010

TROMBOEMBOLIA

Venous Thromboembolism (VTE) Prophylaxis in Surgical Patients
by Steven L. Cohn, MD, FACP
Director, Medical Consultation Service, Kings County Hospital Center, Clinical Professor of Medicine, SUNY Downstate, Brooklyn, NY



Slide 1: VTE Prophylaxis in Surgical Patients



I'm Dr. Steven Cohn, Director of the Medical Consultation Service at Kings County Hospital Center and Clinical Professor of Medicine at the State University of New York Downstate Medical Center in Brooklyn.



Slide 2: Learning Objectives



As far as the learning objectives for this lecture, after taking part in this activity, you should be able to understand the pathophysiology and risk factors for VTE, stratify surgical patients according to their risk for VTE if they don't get prophylaxis, and apply the latest ACCP guidelines for preventing VTE in surgical patients.



Slide 3: Incidence, Pathophysiology, & Risk



I'll begin by talking a little bit about the incidence of pathophysiology and risk factors for venous thromboembolism.



Slide 4: Venous Thromboembolism



SIf you look at the annual incidence of VTE in the United States, various numbers have been thrown around, but they range from about 600,000 to 900,000 cases of VTE with an estimate of 200,000 to 300,000 deaths due to DVT and pulmonary embolism. A significant number of patients are at risk for VTE in United States hospitals: over 7 million on the medical service and over 4 million on the surgical service, which represented about a third of the hospital discharges at that time. What's important to note is that about two-thirds of VTE cases and deaths are felt to be hospital acquired. This doesn't mean that they're diagnosed or occur in the hospital, but they are somehow related to having been hospitalized or having had a surgical procedure, and it's felt that pulmonary embolism is the leading preventable cause of hospital death.



Slide 5: Surgeon General's "Call to Action"



In 2008, the Surgeon General issued a call to action on DVT and PE. He wanted a plan to reduce the numbers of VTE cases by increasing awareness about VTE using evidence-based practices for DVT prevention, and he also asked for more research on the causes, prevention, and treatment of DVT.



Slide 6: Long-Term Complications



When you look at the problem of DVT, some of my surgical colleagues feel "What's the big deal?" The patient gets a DVT or a PE-as long it's not fatal, they'll make the diagnoses, and they'll treat the patient, and that's the end of it. But, as an internist, I get to see patients on a much longer term and see some of the long-term complications after having an episode of a DVT or PE. And, as illustrated on this slide, after a first episode of DVT or PE, complication rates increase with time, and over a 5- to 10-year period, there is a chance of recurrent DVT or PE somewhere between 20% and 30%. The same number will develop post-thrombotic syndrome over the next 5 to 10 years and occasionally a patient will develop pulmonary hypertension after a single episode of a pulmonary embolism, so that's the reason you try to prevent these long-term complications. You don't let the patient get the first one; you give DVT prophylaxis.



Slide 7: Virchow's Triad



If we look at the underlying reasons why patients get clots, you can see that there are three basic pathophysiologic mechanisms based on Virchow's triad: stasis, intimal injury and a hypercoagulable state. On this slide, you see some of the risk factors grouped according to what their most likely basis is, although there is some overlap, and this is not an all-inclusive list. So, as far as risk factors for stasis, you can see that they are older age (and older means over the age of 40 in surgical patients), immobility (and even if a patient could walk when they came to the hospital, we often make them immobile with our orders), and bed rest or bed rest with bathroom privileges where they have nowhere to go and they stay in their rooms and they go from the bed to the chair to the bathroom and back-that's considered to be immobile. Other reasons for stasis include immobilization of a leg, paralysis, stroke, or spinal cord injury. Hyperviscosity and polycythemia also cause stasis. Heart failure and severe COPD, two of the most common reasons for hospitalization, lead to stasis. Anesthesia-whether it's general, spinal, or epidural-causes stasis, and obesity is another risk factor. On the hypercoagulable side, cancer and chemotherapy are listed, as well as high estrogen states, which include pregnancy, oral contraceptives, and hormone replacement therapy; inflammatory bowel disease; nephrotic syndrome; sepsis; and thrombophilias. As far as endothelial injury is concerned, direct injury caused by surgery, residual damage from a previous VTE, the presence of central lines, or trauma all cause tissue injury. So, these are the underlying mechanisms for why patients are at risk for developing clots.



Slide 8: Outpatient and Inpatient VTE Are Linked



I mentioned on an earlier slide that two-thirds of VTEs are felt to be hospital acquired. Now, this slide is looking at outpatient and inpatient VTEs and showing how they are linked. There are almost 2,000 patients here in Worcester, Massachusetts, who had a DVT or a PE. The majority, 74%, presented as outpatients, but when you look at some of these outpatients, you can see that 23% of these outpatients had recent surgery, and only 62% received any form of VTE prophylaxis. Most of these recurrences or occurrences were within 30 days after the patient was discharged from the hospital. So when someone says, "How can you prevent a DVT when they first show up in my emergency room?" the answer is to give prophylaxis when they are hospitalized. The majority of these VTEs were diagnosed in the three months following hospitalization, more than occurred during the hospital stay itself.



Slide 9: Risk Stratification & Current Guidelines



Now, I'd like to move on to VTE prophylaxis, and we'll talk about risk stratification and current guidelines.



Slide 10: Prophylaxis Options



There are various options available for VTE prophylaxis, and they can be grouped into two big categories: one is pharmacologic and the second is mechanical. Pharmacologic, in general, is preferred over mechanical unless there's a high bleeding risk. In the pharmacologic options, you have unfractionated heparin, either given q.8 or q.12 hours; warfarin, primarily for orthopedic patients; low-molecular-weight heparins; Xa inhibitors; oral-thrombin inhibitors; and aspirin, which I have in parentheses because it's not recommended by the ACCP. On the mechanical side, you have early ambulation, which all patients should be encouraged to do if possible; the use of graded elastic stockings; intermittent pneumatic compression devices or sequential compression devices; and IVC filters, which currently have no primary role for prophylaxis.



Slide 11: VTE Risk & Recommended Prophylaxis



As far as categories for risk, the ACCP guidelines in 2008 redefine their levels of risk into three categories of low, moderate, and high based on the likelihood a patient would get a DVT or PE if they were not given prophylaxis. They defined low risk as patients who have a risk less than 10%, and this included patients undergoing minor surgery, who are mobile, and medical patients who are also fully mobile. The prophylaxis options in this category included no specific therapy, just early ambulation. These people, again, were at low risk. The moderate risk group, defined as a VTE risk without prophylaxis between 10% and 40%, include most of the surgical patients we see who are having general surgery, open gynecologic surgery, or urologic surgery, and our medical patients who are at bed rest or considered to be so-called "sick." The options here include the use of low-molecular-weight heparin, unfractionated heparin, or fondaparinux. The asterisk next to fondaparinux indicates that it's not FDA approved for the medical patients. As far as the high-risk group, these have an estimated risk of developing a VTE between 40% and 80% without prophylaxis. It includes major orthopedic surgery, for example hip and knee replacement; hip fracture surgery; major trauma; and spinal cord injury patients. And here there is really no role for unfractionated heparin because it doesn't work as well as the three things that are recommended, and they include low-molecular-weight heparin, fondaparinux, or oral vitamin K antagonist, which in the United States is warfarin targeted to an INR between 2 and 3. What the ACCP guidelines also say is that if you have moderate or high risk of developing a VTE but you have a high bleeding risk, you should use mechanical devices instead of pharmacologic prophylaxis. This includes IPCs or graded compression stockings. For a patient who is considered to be high risk, you should also combine modalities, using pharmacologic plus mechanical methods.



Slide 12: Primary Prevention Surgical Patients



Now I'll discuss some of the primary prevention recommendations in surgical patients and will look at various subgroups based on ACCP guidelines.



Slide 13: Prevention in General Surgery



For prevention of VTE in the general surgical patient, this is similar to what I just discussed, based on the three levels of risk. However, they subdivide the moderate risk group a little bit. So, patients who are at low risk, those undergoing minor surgery who have no additional risk factors, a lot of the ambulatory surgery patients don't need any specific therapy, just early ambulation. The moderate risk group, they subdivide, sort of, by including patients that have major procedures for benign disease as opposed to higher risk subgroup: major procedures for cancer. For benign disease, you can use low-molecular-weight heparin, low-dose unfractionated heparin where they do consider b.i.d. dosing to be acceptable, or use fondaparinux. However, for the higher risk subgroup for cancer surgery, they recommend low-molecular-weight heparin, if you do use unfractionated heparin, it should be three times a day, or fondaparinux. The highest risk group for general surgery will be those patients who have multiple risk factors, and here, in addition to what they recommended above, they suggest combining it with mechanical devices. Once again, if the patient has a high bleeding risk, you should use mechanical devices, pneumatic compression device, or graded compression stockings rather than pharmacologic prophylaxis.



Slide 14: Prevention in Gynecologic Surgery



For DVT prophylaxis in gynecologic surgery, some of the risk factors here include patients who tend to be older, they may have had a previous VTE, they may have a malignancy, and they are undergoing abdominal procedures very frequently. This is also similar to the general surgical patient I just discussed. Those patients considered to be at low risk going for minor procedures with no additional risk factors just get early ambulation. Those going for major surgery for benign disease without other risk factors get low-molecular-weight heparin, unfractionated heparin, or IPCs, and those going for more extensive surgery for malignancy or those who have additional risk factors get one of those three things or fondaparinux, ideally plus pneumatic compression devices or graded compression stockings. In selected patients who are at high risk who are undergoing surgery for malignancy, there is also a recommendation to continue prophylaxis with low-molecular-weight heparin for up to 28 days, so-called "extended prophylaxis."



Slide 15: Duration of Prophylaxis



As far as the duration of prophylaxis is concerned, when is extended prophylaxis indicated? Extended prophylaxis means going beyond the 7 to 10 days that was a typical length of duration in the studies. For both general surgery and gynecologic surgery, there are recommendations to continue this prophylaxis for up to 28 days, using low-molecular-weight heparin in selected high-risk patients that have major cancer surgery or had a previous VTE.



Slide 16: Prophylaxis after Cancer Surgery



The evidence for extended prophylaxis after cancer surgery is shown on this slide, which combines results of three studies with low-molecular-weight heparins. You can see that there is significant reductions with statistically significant P-values for reduction in DVT overall, as well as proximal DVT, and nonstatistical decreases but a trend toward a decrease with symptomatic VTE. This is where the recommendation from the ACCP comes from.



Slide 17: Prevention in Urologic Surgery



As far as urologic surgery is concerned, some of the risk factors involved here include patients undergoing open procedures, patients tending to be older, they may have malignancy, the duration of the procedure can be a factor, and often they are operated on in the dorsal lithotomy position. So, if you look at the level of risk and the procedure they're going for and what the prophylaxis options are, if it's a transurethral procedure or other low-risk GU procedures, you don't need anything but early frequent ambulation. For most major open procedures, they recommend unfractionated heparin, either two or three times a day, IPCs, low-molecular-weight heparin, fondaparinux, or a combination of pharmacologic and mechanical methods, depending on the patient's risk factors. On the bottom you see urologic surgery with active bleeding or high bleeding risk; they recommend mechanical devices again, mainly IPCs.



Slide 18: Prevention in Laparoscopic Surgery



Some of the risk factors involved with laparoscopic surgery include longer surgical times than an open procedure; pneumoperitoneum; and reverse Trendelenburg position, which can increase venous stasis. But overall, the risk appears to be fairly low with laparoscopic surgery and, for that reason, the ACCP recommends that patients undergoing entirely laparoscopic procedures with no additional risk factors only get frequent ambulation. On the other hand, if they do have additional risk factors-for example, it's a laparoscopic procedure for cancer-then they should get either low-molecular-weight heparin, unfractionated heparin, fondaparinux, or pneumatic compression devices.



Slide 19: Prevention in Bariatric Surgery



As far as bariatric surgery is concerned, once again the ACCP recommends for inpatient bariatric surgery the use of low-molecular-weight heparin, low-dose unfractionated heparin t.i.d., or fondaparinux, or a combination of pharmacologic and physical methods. They also go on to suggest using a higher dose of low-molecular-weight heparin or unfractionated heparin in morbidly obese patients.



Slide 20: Prevention in Neurosurgery



For neurosurgery, factors that increase risk of developing a VTE include intracranial surgery, malignant tumors, longer duration of surgery, development of leg weakness, or older age. What the ACCP recommends for major neurosurgical procedures is primarily the use of mechanical devices, intermittent pneumatic compression, or the use of postoperative low-molecular-weight heparin or low-dose unfractionated heparin. And in patients who are undergoing neurosurgery with very high risk, they also recommend the use of mechanical combined with pharmacological methods postoperatively. The idea is that a little bleeding in intracranial surgery can be a potential disaster, so they like to stay away from the pharmacological methods preoperatively. But in those patients at high risk, they use pharmacologic methods in addition to mechanical methods postoperatively when the bleeding risk has gone down.



Slide 21: Prophylaxis in Orthopedic Surgery



Next, we'll look at VTE prophylaxis in orthopedic surgery. These are the patients that have the highest risk of developing a postoperative DVT or PE, and the prophylaxis is a little bit different.



Slide 22: Thromboprophylaxis for Hip/Knee Replacement



This slide is a little busy, but it shows the pharmacologic thromboprophylaxis for hip or knee replacement that is recommended by the ACCP, as well as the AAOS (the American Academy of Orthopedic Surgeons). What the American College of Chest Physicians recommends is the use of either low-molecular-weight heparin, fondaparinux, or warfarin with a target INR between 2 and 3, and it's a grade 1 recommendation with a level of evidence that is considered to be A. They also go on to say if the patient is at high bleeding risk for hip replacement, you should use mechanical devices, either venous foot pump or intermittent pneumatic compression and the same thing for a total knee replacement, and you can see the grade and recommendation and level of evidence. On the right-hand side, the American Academy of Orthopedic Surgeons tries to define risk solely for PE, not for a DVT, and they divided into a standard risk for PE versus elevated risk and the same for a major bleeding risk. They have similar recommendations with the exception that they include aspirin, which the ACCP does not recommend, and they recommend that for patients who are at standard risk for PE with a standard bleeding risk, standard risk with an elevated bleeding risk, and elevated risk of PE with an elevated bleeding risk. You can see the corresponding grades of recommendation and levels of evidence.



Slide 23: Prophylaxis in Orthopedic Surgery



As I mentioned earlier, these orthopedic patients undergoing major orthopedic procedures for joint replacement or hip fracture surgery have the highest risk of developing a postoperative VTE, and you can see here on the placebo group, it ranges between 40% and 60% without prophylaxis. Aspirin reduces this somewhat, as you can see in the numbers here-this is a composite slide-as does warfarin. It seems to get a little bit better with low-molecular-weight heparin, and the best is with fondaparinux. However, there is some potential increased risk of bleeding with fondaparinux in the replacement surgery.



Slide 24: Prophylaxis for Orthopedic Surgery



Now, let's look at how you use these options for prophylaxis for the orthopedic surgery patient. If you choose to use low-molecular-weight heparin, in the United States this is typically started the morning after surgery because most of these operations are done under neuraxial anesthesia, either spinal or epidural anesthesia, and it's typically started at least two hours after the removal of an epidural catheter, if that's used as well. The idea here is to make sure the effect of the low-molecular-weight heparin is gone before you place a spinal needle or several hours after you remove an epidural catheter. If you use an enoxaparin, the dosing in the United States is 30 mg q.12 hours started the morning after surgery. The European dose, when they use general anesthesia, is 40 mg once a day started 12 hours before surgery. If you use dalteparin the dose is 5,000 International Units once daily. For fondaparinux, this is usually started six hours after surgery, not the next day, with a 2.5 mg dose, and they give the next dose the following morning and once daily after that. For warfarin, it's typically started the evening before surgery with a dose between 5 and 10 mg without the need for concomitant heparin. You then give the patient 5 mg the night they have the surgery and titrate to a target INR of approximately 2.5 with a range between 2 and 3. Most of these are also combined with the use of mechanical devices and pneumatic compression devices. It should be noted that unfractionated heparin and aspirin are not recommended by the ACCP guidelines for a total hip replacement or a total knee replacement.



Slide 25: New Oral Anticoagulants with Warfarin



There are a number of new oral anticoagulants on the market, actually in Canada and Europe, that have not yet been FDA approved, but they look pretty promising, particularly for the use of orthopedic surgery prophylaxis. They will have other indications as well, and this slide is looking at the comparison between these new drugs and warfarin. It shows what the target is, and the 10A inhibitors include rivaroxaban and apixaban, and a direct thrombin inhibitor is dabigatran. You can see how they are dosed either once a day or twice a day. These new drugs do not require any monitoring for their anticoagulant effect. You can see their renal clearance and their interactions with other drugs as well, but the idea is that these newer drugs will be a fixed dose once or twice a day without the need for any monitoring.



Slide 26: Duration of Prophylaxis



In orthopedic surgery, the duration of prophylaxis is even more important, and there are stronger recommendations for extended prophylaxis after hip fracture surgery and total hip replacement and somewhat lesser recommendations for the same in total knee replacement. So, the American College of Chest Physicians recommends that beyond 10 days and up to 35 days-and it's a 1A recommendation for hips-using either low-molecular-weight heparin, vitamin K antagonists, or fondaparinux. The reason for extended prophylaxis in orthopedic surgery is that the risk of a DVT or PE for hip surgery extends out well beyond two weeks with a peak probably between two and three weeks, but a risk extending up to three months. For knee replacement, the peak is about 7 to 10 days, so it doesn't have the strength for the recommendation that they have for hips, but it still extends out a little bit longer, and the recommendation is to use extended prophylaxis for both hip replacement, hip fracture surgery, and also consider it for knee replacement.



Slide 27: Major Orthopedic Surgery



This slide is basically a summary slide of the prophylaxis recommendations from the ACCP for major orthopedic surgery. It shows total hip replacement, total knee replacement, and hip fracture surgery, as well as the extended prophylaxis that is recommended, and it looks at the three drugs that they recommend as well, giving the level of evidence and the grade of recommendation.



Slide 28: Prevention of VTE in Lower Extremity Injuries



Somewhat controversial is the recommendation to prevent VTE in lower extremity injuries distal to the knee. The risk factors for developing a clot here include fracture, which is a higher risk than just soft-tissue injury; the location; the proximity of the fracture to the knee; the age of the patient; and the presence of obesity. And although prophylaxis with low-molecular-weight heparin has been shown to decrease asymptomatic DVT and some European countries recommend it, the ACCP actually does not recommend prophylaxis for these patients. So they say for lower extremity injuries, which includes distal extremity fractures, no routine thromboprophylaxis is recommended.



Slide 29: Prevention of VTE in Spine Surgery



Spine surgery factors that are associated with increased risk include increased age, lumbar surgery as opposed to cervical spine surgery, the use of an anterior approach, manipulation of the iliac veins or inferior vena cava, the presence of malignancy, a prolonged operation, or the patient who has reduced mobility. What the ACCP recommends here, if the patient has no additional risk factors, they say only early and frequent ambulation. If they have additional risk factors, where it's a more complicated procedure, they recommend the use of postoperative unfractionated heparin, low-molecular-weight heparin, or pneumatic compression devices. An alternative is graded compression stockings. In a patient with multiple risk factors, they recommend the combination of pharmacologic and mechanical methods, but again, they recommend the use of pharmacologic prophylaxis in the postoperative setting, not preoperative.



Slide 30: Prophylaxis in Special Patient Populations



Now, there are a few caveats that you need to know about as far the use of certain prophylaxis in special patient populations, and the two things I'll be discussing are renally impaired patients and obese patients.



Slide 31: Renal Impairment Recommendations



As far as renal impairment recommendations are concerned, the ACCP guidelines say that you should consider renal function when making decisions about the use of or the dosing of low-molecular-weight heparin, fondaparinux, or any other antithrombotic drugs that are cleared by the kidneys. The risk of bleeding is increased in the elderly and patients with diabetes, and pay attention to those patients who also have other risks for bleeding. And the options here include voiding anticoagulants that bioaccumulate with renal impairment, using a lower dose of that agent, or monitoring the drug level or its anticoagulant effect, meaning anti-10A levels.



Slide 32: Renal Impairment and the Use of LMWH



As far as renal impairment and the use of low-molecular-weight heparin, what they have found is that these anticoagulants may accumulate in patients who have renal impairment and can increase bleeding risk. They suggest that standard weight adjusted doses of enoxaparin be avoided in patients whose creatinine clearance is less than 30, as they were correlated with an increase in anti-10A levels and an increased bleeding risk in this setting. They say to consult the manufacturer's dosing guidelines for any anticoagulant cleared by the kidneys. For enoxaparin, they do suggest instead of using 40 mg once a day that you use 30 mg once a day in patients whose creatinine clearance is less than 30 but they are not on dialysis. There is insufficient data available to draw conclusions about the use of tinzaparin, dalteparin, or other low-molecular-weight heparins when the patient's creatinine clearance is less than 30. Fondaparinux does tend to accumulate in renal impairment and is contraindicated with a creatinine clearance less than 30.



Slide 33: Prophylaxis in Obesity



What's been noted in DVT prophylaxis in the obese patient is that you can use low-molecular-weight heparin at non-obese doses or the standard dose with multimodal therapy. However, in 2008, the ACCP made a recommendation that you should consider using a higher dose in morbidly obese patients, but unfortunately, they did not recommend what that higher dose actually is. They were just saying that sometimes the standard dose may not be as effective in morbidly obese patients.



Slide 34: Improving Prophylaxis Rates



So, with pulmonary embolism being the number one cause of preventable death in hospitalized patients, what can we do to improve VTE prophylaxis rates?



Slide 35: Patients at Risk Remain Unprotected



Well, despite the evidence and despite what I have been talking about today, patients at risk remain unprotected, meaning they don't get prophylaxis or they don't get appropriate prophylaxis, and this is the ENDORSE trial or registry looking at sort of a snapshot in time around the globe of medical and surgical patients, approximately 68,000 patients. They looked at how many patients were at risk for VTE and, of these at-risk patients, how many of them were receiving prophylaxis according to the ACCP recommendations. Only 40% of the medical patients and 59% of the surgical patients received prophylaxis that was recommended. This is not considered to be acceptable.



Slide 36: Surgical Care Improvement Project



One of the things that was done to try to improve these rates of prophylaxis was part of the surgical care improvement project. They have a couple of performance measures looking at VTE prophylaxis. SCIP 1 looks at surgery patients who had recommended VTE prophylaxis ordered, and SCIP 2 looks at surgical patients who actually received appropriate prophylaxis within 24 hours of the time they had their surgery. These are publicly reportable and can be tracked online so you can see what your hospital performance is. They were planning to institute SCIP 3 and 4, looking at postoperative complications, either a PE or DVT within 30 days of surgery, but these have been put on hold at this point.



Slide 37: Joint Commission/NQF Draft



Separate from the SCIP project, the Joint Commission and NQF plan to institute a number of measures looking at VTE and VTE prophylaxis that were supposed to have been started in 2009, but have now been pushed off to 2010. Here they're planning to look at whether a patient has a risk assessment or receives prophylaxis within 24 hours of admission to the hospital or of being transferred to and from the ICU. They're looking at the use of anticoagulation with heparin or low-molecular-weight heparin and how you overlap your therapy with warfarin. They're looking at patients who were treated with unfractionated heparin, as far as the dosing, or using a nomogram and monitoring platelet count, as well as looking at VTE discharge instructions on patients who go home on Coumadin to tell them about diet and food and drug interactions, about risk of bleeding, and about coming back to monitor INR. And they're also going to be looking at the incidence of potentially preventable VTE. This means if you get a DVT or PE in the hospital and you didn't get prophylaxis or didn't get appropriate prophylaxis, this is something that will be tracked. We currently do this in New York State. It's currently called NYPORTS, and it's an event that we have to report, even if the patient did get appropriate prophylaxis. So any patient who gets a DVT or PE in the hospital in New York State gets reported to this agency.



Slide 38: Increasing Use Prophylaxis



As far as what strategies can be used to increase use of VTE prophylaxis, this is meta-analysis that basically showed that passive strategies alone-in other words, giving guideline dissemination or me just talking to you-may not be enough. There is not going to be good adherence to the guidelines. You need to use a more proactive strategy and, ideally, if you have a computer-decision support system, you can send out reminders or you can monitor who is getting prophylaxis and who isn't. By doing these things that are more proactive or combining multiple strategies, you can significantly increase rates of prophylaxis. This has been shown in a number of studies.



Slide 39: Summary



So, in summary, what I've shown is that venous thromboembolism is a prevalent disorder associated with significant morbidity and mortality. Most surgical patients are at risk, yet prophylaxis is still underutilized. What you need to do is risk-stratify patients based on the type of surgery that's planned, as well as any other risk factors that they may have, and then prescribe appropriate prophylaxis as recommended by the ACCP guidelines. By doing this, we can hopefully decrease the incidence and occurrence of postoperative DVT and PE and improve patient outcome.