doi: 10.1161/CIRCULATIONAHA.106.674663
(Circulation. 2007;115:e302-e307.)
© 2007 American Heart Association, Inc.
Clinician Update |
Prevention of Pulmonary Embolism in General Surgery Patients
From the University of Western Ontario, London, Ontario, Canada (U.Z.), and Cardiovascular Division, Brigham and Women’s Hospital (S.P., S.Z.G.) and Hematology/Oncology Division, Children’s Hospital (S.P.), Harvard Medical School, Boston, Mass.
Correspondence to Samuel Z. Goldhaber, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail sgoldhaber{at}partners.org
Key Words: anticoagulants • embolism • heparin • prophylaxis • risk factors • surgery • thrombosis
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Introduction |
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Case Presentation: A 29-year-old woman presented to the emergency department with complaints of pleuritic chest pain, fever, and left ankle swelling and tenderness. Cardiac examination was normal except for tachycardia. A chest computed tomography scan with contrast demonstrated extensive bilateral pulmonary emboli. Thirteen days previously, an intoxicated driver with multiple prior convictions for driving under the influence of alcohol crashed head-on into her car at a high speed. She was 8 months’ pregnant and suffered the loss of the child. She spent 7 days in the hospital and underwent cesarean section, exploratory laparotomy, and splenectomy. No preoperative pharmacological prophylaxis against venous thromboembolism (VTE) was administered.
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Epidemiology |
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TopIntroductionEpidemiologyNatural HistoryRisk FactorsProphylaxisCase PresentationReferences |
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VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and common complication of general surgery.
A new era in the postoperative management of surgical patients began in 1975 when the effectiveness of low-dose heparin in preventing postoperative DVT and PE was established by the pivotal International Multicenter Trial.1 The dose was 5000 U subcutaneously every 8 hours, with the first injection administered 2 hours before the skin incision. Compared with control, the incidence of DVT in patients receiving heparin decreased from 24.6% to 7.7%. Similarly, the incidence of autopsy-proven PE was reduced 8-fold. The results of this trial introduced and validated the concept of using low-dose heparin to prevent postoperative VTE. This trial revolutionized surgical practice. By 1994, 90% of North American general surgeons reported the routine use of thromboprophylaxis.2
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Natural History |
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Most postoperative DVT originates in the deep calf veins, primarily within the valve cusps. Most thrombi remain confined to the calf. Propagation into the proximal veins increases the risk of PE. Symptoms and signs of postoperative VTE such as mild hypoxia or low-grade fever are frequently nonspecific. Moreover, clinical manifestations of postoperative VTE may not occur until several weeks after general surgery.3 Consequently, most cases are not suspected clinically.
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Risk Factors |
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Surgery-Related Factors
Surgery-related risk factors for VTE include infection, immobilization, and dehydration, in addition to the duration and type of surgery.4 Patients undergoing outpatient surgery are at relatively low risk.4 The incidence of VTE associated with day surgery for inguinal hernia repair is a modest 0.04%.5 Similarly, minor abdominal surgery involving the abdominal wall or appendix carries a relatively low VTE risk of 0.1% to 0.6%.6 In contrast, major general surgery such as liver, pancreatic, gastric, or bowel surgery carries a higher risk, with 0.8% to 1.7% of patients developing PE.7
Obese patients who undergo bariatric surgery have traditionally been categorized as at high risk for VTE, with PE being one of the most common causes of postoperative death.8 However, prospective studies indicate a modest rate of symptomatic PE, ranging from 0.8% to 1.2%.8,9
VTE risk after laparoscopic surgery has been controversial. A meta-analysis of 153 832 patients who undergo laparoscopic cholecystectomy revealed a rate of 0.03% for postoperative DVT and 0.02% for fatal PE compared with a risk of 5% and 0.4%, respectively, for the conventional open surgical procedure.10,11 Studies of other laparoscopic procedures, including Nissen fundoplication, colon resection, and splenectomy, have found a low frequency of VTE.12–14
The type and duration of anesthesia also play a role in the development of postoperative DVT. General anesthesia has been associated with higher risk of DVT than spinal or epidural anesthesia.15 A study of orthopedic surgery patients found that duration of anesthesia >3.5 hours was a strong risk factor for postoperative VTE regardless of the route of anesthesia.16
Patient-Related Factors
Patient-related risk factors include cancer, advancing age, previous VTE, obesity, varicose veins, and estrogen use.4 Patients with malignancy who undergo surgery have at least twice the risk of postoperative DVT and >3 times the risk of fatal PE as noncancer patients who undergo similar procedures.4 Advancing age (>40 years of age) also is associated with a steady increase in VTE risk by 
20% per decade after general surgical procedures such as cholecystectomy and appendectomy.17
Formal risk assessment models that combine patient-related and surgery-related factors into a composite risk estimate have been proposed to optimize stratification of surgical patients into levels of VTE risk (Table 1). However, these models are complex, time-consuming, and unwieldy. They do not provide comprehensive guidance for all patient groups, and they have not been validated in clinical practice.18 We therefore advise a more straightforward approach: a default order to implement routine pharmacological prophylaxis against VTE in all patients who undergo major general surgery. Exceptions to the default can be made on the basis of bleeding risk and other special circumstances.
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Prophylaxis |
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Guidelines from the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy recommend that every hospital develop a formal strategy such as a written thromboprophylaxis policy to prevent thromboembolic complications.4 Several agencies, including the National Quality Forum,19 the Leapfrog Group,20 and the Surgical Care Improvement Project,21 also have developed performance measures regarding VTE prophylaxis in surgical patients (Table 1).
Specific guidelines for prophylaxis have been issued by the American College of Chest Physicians, the Surgical Care Improvement Project, the International Union of Angiology,22 and the National Comprehensive Cancer Network23 (Table 2). There is universal consensus for the use of fixed, low-dose unfractionated heparin (LDUH) or low-molecular-weight heparin (LMWH) for VTE prophylaxis in general surgery.
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The purpose of thromboprophylaxis is to avert the formation of thrombin by preventing the initiation of intravascular coagulation. Trace amounts of heparin and LMWH can accelerate the antithrombin-mediated neutralization of activated factors IX, XI, XII, and X several-fold, thereby limiting thrombin generation.24,25 Hence, venous thrombosis can be prevented by halting the development of a hypercoagulable state that would otherwise occur during and after surgery.26 This forms the basis for the use of low-dose heparin in thromboprophylaxis. Heparin is a potent catalyst of the antithrombin-mediated inhibition of factor Xa in low doses, yet it also inhibits thrombin by forming an inactive heparin-thrombin-antithrombin complex when used in higher doses. Heparin also stimulates the release of the tissue factor pathway inhibitor from the vascular endothelium, which in turn inhibits the tissue factor–mediated coagulation pathway27 (the Figure and Table 3).
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, catalytic action; and 
, inhibitory action.
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A large meta-analysis demonstrated that a regimen of 5000 U of subcutaneous unfractionated heparin started 2 hours before surgery and continued every 8 or 12 hours reduced the rates of DVT (from 22.4% to 9.0%), symptomatic PE (from 2.0% to 1.3%), fatal PE (from 0.8% to 0.3%), and all-cause mortality (from 4.2% to 3.2%) compared with control.28 Another meta-analysis showed that LDUH is not associated with increased rates of major bleeding.29
LMWH offers an efficacy and safety profile that is at least equivalent to that of LDUH. A meta-analysis of 51 studies involving >48 000 patients undergoing general surgery found no statistically significant differences in rates of asymptomatic DVT, clinical PE, death, major hemorrhage, and wound hematoma between LMWH and LDUH.30 Advantages of LMWH are its greater ease of administration, lower risk of heparin-induced thrombocytopenia, and more predictable anticoagulant effect.4
The newest thromboprophylactic agent evaluated in general surgical patients is fondaparinux, a synthetic selective factor Xa inhibitor. There have been no reported cases of heparin-induced thrombocytopenia with fondaparinux use. When fondaparinux was compared with LMWH in a study of nearly 3000 patients undergoing high-risk abdominal surgery, similar rates of VTE (4.6% and 6.1%, respectively) and major bleeding (3.4% and 2.4%, respectively) were observed.31 Thromboprophylaxis with fondaparinux has been studied most extensively in patients undergoing major orthopedic surgery, including hip and knee arthroplasty, and in patients suffering hip fracture. Fondaparinux administered 6 hours after surgery has consistently shown improved efficacy compared with enoxaparin, which is usually administered 12 hours after surgery. A meta-analysis of 4 studies involving >7000 patients concluded that, compared with enoxaparin, fondaparinux significantly reduced the incidence of VTE from 13.7% to 6.8%.32 However, major bleeding was more common in fondaparinux-treated than enoxaparin-treated patients (2.7% and 1.7%, respectively).
The optimal duration of thromboprophylaxis in general surgical patients remains to be clarified. Patients with malignancy appear to benefit from extended prophylaxis, as illustrated by the significant reduction in VTE incidence from 12.0% to 4.8% in patients undergoing surgery for abdominal or pelvic cancer who received enoxaparin for 4 weeks compared with those given it for 1 week of prophylaxis.33
Mechanical compression methods, which include graduated compression stockings, intermittent pneumatic compression, and foot pumps, reduce the risk of proximal vein thrombosis by about one-half and the risk of PE by two-fifths. They also reduce the risk of DVT by about two-thirds when used as monotherapy and by about one-half when added to a pharmacological method.34
A meta-analysis of 2270 postoperative patients, including >427 general surgery patients, found that intermittent pneumatic compression reduced DVT risk by 60% compared with no prophylaxis.35 In laparoscopic surgery, the use of intermittent pneumatic compression has been shown to reverse the compressive effect of pneumoperitoneum on the femoral veins.36 Intraoperative intermittent pneumatic compression is thus strongly recommended by the European Association for Endoscopic Surgery for all prolonged laparoscopic procedures.37
A systematic review and 2 meta-analyses have shown that graduated compression stockings also reduce the relative risk of DVT after general surgery by 66%.38–40 The use of graduated compression stockings, combined with pharmacological prophylaxis, has an additive effect, especially in patients at high risk for VTE.34,40,41
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Case Presentation |
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TopIntroductionEpidemiologyNatural HistoryRisk FactorsProphylaxisCase PresentationReferences |
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This case highlights surgery, trauma, immobilization, and pregnancy as risk factors for VTE. Multiple factors placed this patient in a high-risk category, indicating a strong need for thromboprophylaxis. LDUH or LMWH should have been started 2 hours before surgery and continued postoperatively. This case also demonstrates the nonspecific presentation of VTE in surgical patients and the difficulty of detecting DVT and pulmonary embolism postoperatively.
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Acknowledgments |
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We wish to acknowledge the guidance of Jawed Fareed, PhD, Ajay K. Kakkar, MD, and Arthur A. Sasahara, MD, while preparing this manuscript.
Disclosures
Dr Parasuraman receives clinical research support from Sanofi Aventis. Dr Goldhaber receives clinical research support from Sanofi Aventis, Bristol Myers Squibb, GlaxoSmithKline, and Eisai.
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