Olivier Q. Groot, David W. Polly, Joseph H. Schwab.
Response/Recommendation: Epidural hematoma is a feared yet rare postoperative complication after spinal surgery, with symptomatic rates ranging from 0% to 1.8%. Although there is no published evidence to precisely define the safety of chemoprophylaxis, it seems that postoperative anticoagulants in non-therapeutic doses can be administered without an increased risk of spinal epidural hematoma. Prospective studies are required to better balance the risks and benefits of prophylactic anticoagulants regarding spinal epidural hematomas and Venous thromboembolism (VTE).
Strength of Recommendation: Limited.
Rationale: The key words used in our search of PubMed, Cochrane Library, and Embase were “epidural hematoma”, “spine surgery”, and “venous thromboembolism”. Studies were included if they investigated spinal epidural hematomas and chemoprophylaxis of any sort. Studies were not excluded if they did not clearly report VTE or the method of VTE screening. Case reports and series were excluded. References of included studies were checked. Various data was extracted from the included studies including method of chemoprophylaxis, VTE screening, and rates of postoperative symptomatic VTE and epidural hematoma. In total, 14 studies were included for data extraction after full review.
Spine surgeons must weigh the risks of chemoprophylaxis, which include bleeding and hemorrhagic complications such as spinal epidural hematoma, against the benefits of preventing VTE. Studies report a symptomatic postoperative VTE rate of 1.5% – 31% and symptomatic spinal epidural hematoma of 0% – 1.8%1–5. Both rates are noteworthy, especially considering that epidural hematoma can lead to severe neurologic complications. As a result, precise indication, agent, dose, and timing for prophylaxis following spinal surgery is essential3,6.
In 1998, Agnelli et al.7, compared in a level I, multicenter randomized controlled trial the use of compression stockings (CS) alone (n = 15) to enoxaparin 40 mg daily started within 24 hours for 7 days and CS (n = 31) following elective spinal cord procedures. No patients developed a spinal epidural hematoma and VTE rate was unknown. Not specific to spinal procedures, the authors concluded that enoxaparin combined with CS was more effective in preventing symptomatic VTE than CS alone and did not increase the risk for excessive bleeding following intracranial and spinal procedures.
In a recent 2021 study by Thota et al.8, 888 patients who received anticoagulation were propensity score-matched to 888 patients receiving no anticoagulation in elective spine surgeries. No difference was found in symptomatic VTE rate; however, unplanned reoperation for hematoma were greater for those who received pharmacological anticoagulation (odds ratio [OR] = 7.5, 95% confidence interval [CI] = 2.0 – 28.3, p <0.01).
Cox et al.9, compared VTE and epidural hematoma rate before (provider dependent, 24 hours after surgery) and after a protocol change (5,000 U heparin administered subcutaneously 3 times daily, with the first dose given immediately postoperatively). VTE rate decreased in the more aggressive protocol (3.3% vs. 1.5%; p <0.01) and no difference was found in epidural hematoma occurrence (0.6% vs. 0.4%; p =0.58). Gerlach et al.10, retrospectively included 1,954 spinal procedures on different levels. All patients received routinely 0.3 mL nadroparin within 24 hours of surgery and compression stocking. Only 1 (0.05%) patient had a DVT, and 8 (0.4%) patients developed epidural hematoma, of which 3 patients were discharged with residual neurological impairment. The authors state that early nadroparin is safe and is not associated with an increased risk of postoperative epidural hematoma.
Uribe et al.11, examined delayed postoperative spinal epidural hematoma, defined as 3 days after surgery, in 4,018 patients that awoke from surgery neurologically unchanged. No standard prophylaxis protocol was used and VTE events were not investigated. Seven (0.2%) patients developed a spinal epidural hematoma of which 4 had received subcutaneous heparin. Dhillon et al., compared 1,904 (28%) patients who received various anticoagulants with 4,965 (72%) patients who received none. The risk of epidural hematomas in both groups was low (both 0.2%; p =0.62). The authors state that administering 5,000 U of heparin, 40 mg of enoxaparin, 2,500 or 5,000 U of dalteparin, or 2.5 mg of fondaparinux within 3 days of surgery was safe for patients undergoing spinal procedures.
Most studies suggested no difference in epidural hematoma rates between postoperative chemoprophylaxis and no prophylaxis4,5,7,9–18, except for Hohenberger et al.19. This retrospective study investigated epidural hematomas in a matched 1:3 case-control study of 6,024 patients undergoing spinal decompression surgery. Forty-two patients with an epidural hematoma were matched with 126 patients with the same surgical procedure, year, sex, and age. Anticoagulation use (acetylsalicylic acid, coumadin, and rivaroxaban) were associated with an increased risk of epidural hematomas (OR, 3.32 [1.50 – 7.38]; p <0.01). However, the VTE rate was not provided, and controlling for confounding factors was not performed. In three similar case-control studies, use of anticoagulants was not associated with an increased risk for epidural hematomas. (Awad, Kao, and Wang)20–22. For instance, a similar 1:3 case-control study demonstrated that 32 patients with and 102 matched controls without spinal epidural hematoma received respectively 41% (13/32), and 51% (52/102) anticoagulation20.
Of interest to note is the study from Cunningham et al.23, that investigated not the influence of postoperative but preoperative chemoprophylaxis on VTE and epidural hematoma rate. In 3,870 elective spinal procedures, 37% (1,428) received preoperative chemoprophylaxis. Nineteen (0.5%) patients had a VTE of whom 9 (47%) had preoperative chemoprophylaxis (p = 0.35). Sixteen (0.4%) patients developed a spinal epidural hematoma, of whom 7 (44%) received preoperative heparin 5,000 units subcutaneously (p = 0.61). The authors conclude that preoperative chemoprophylaxis does not influence the rate of VTE and spinal epidural hematomas.
Several studies identified risk factors for development of spinal epidural hematomas, including perioperative transfusion13, high intraoperative blood loss (> 1 liter)20, pathologic coagulation values, cigarette smoking19, intraoperative use of gelfoam for dura coverage, postoperative drain output22, increased age, obesity, multilevel surgery, and dural tear repair24. Although no studies have specifically investigated anticoagulation use in these high-risk patients, one may want to refrain from administering chemoprophylaxis.
Conclusions from the included studies are difficult given the heterogeneity of methods of prophylaxis and VTE screening, surgical procedures, and patient population. In particular, the timing and dose of chemoprophylaxis vary between studies or are not specified. Furthermore, quality of the individual studies is poor, and the level of evidence is low. The fact that spinal epidural hematomas are relatively rare and potentially life-threatening further complicates investigation of this outcome in a meaningful way3. For example, a clinical trial design comparing two different prophylaxis strategies would require 18,519 patients (difference 0.2% vs. 0.1%) or 1,002 patients (difference 3.6% vs. 1.8%) for 80% power.
In view of these limitations, future research should provide granular data on type, dosage and timing of anticoagulants and stratified epidural hematoma results by indication and chemoprophylaxis usage. Given the severe neurologic complications of epidural hematoma, prospective studies are also needed to delineate the safe use of various anticoagulants after surgery as well as their ideal timing and dosage.
Table 1: Characteristics of included studies (n = 13)
|Author, year||Level of evidence||Patients||Type of surgery||Chemoprophylaxis||Methods of screening||VTE|
|Epidural hematoma %(n)|
TED + LMWH within 24 hours
|Routinely imaging on day 8||NA|
|Al-Dujaili, 20124||IV||158||NS||CS + LMWH 40 mg within 12 h||Clinically + routine US||DVT = 0.6% (1)||1.8% (3)|
|Amiri, 201312||IV||4,568||Various||Anticoagulant therapy within 24 h||NS||NA||0.2% (10)|
|Cloney, 201813||IV||6,869||Various||Various 28% (1,904); none 72% (4,965)*||NS||2.5% (170)||0.2% (13)|
|Cox, 20149||IV||941 992||NS||CS + 5,000U heparin 3x daily after 24h Provider dependent 24 h after OR||NS||3.3% (31); DVT = 2.7% (25); PE = 0.6% (6) 1.5% (15)||0.6% (6) 0.4% (4)|
|Dhillon, 201714||IV||1,904 4,965||Various||Chemoprophylaxis#|
|NS||3.6% (69); DVT = 3.2% (60); PE = 0.8% (15)|
2.0% (101); DVT = 1.7% (82); PE = 0.6% (30)
|0.2% (4) 0.2% (9)|
|Dickman, 199215||IV||104||Posterior pedicle|
|PCS||NS||DVT = 2.9% (3)||1.0% (1)|
|Gerlach, 200410||IV||1,954||Various, multilevel||LMWH within 24 hours + CS||Clinically||DVT = 0.1% (1)||0.7% (13)|
|Groot, 20195||IV||637||Spinal metastases||Various 86% (548); none 14% (89)||Clinically||11% (72); DVT = 6.1% (40); PE = 6.0% (38)||1.1% (7)|
|Park, 201916||IV||2,1261||Various||Various 7.9% (1,678); none 92.1% (19,583)^||NS||2.1% (444); DVT = 1.7% (370): PE = 0.4% (84)||0|
|Platzer, 200617||IV||978||Trauma||LMWH (792); LMWH + CS (153)||Clinically||2.2% (22); DVT = 1.7% (17); PE = 0.9% (9)||0|
|Uribe, 200311||IV||4,018||NS||NS; 4 SEH cases with SCH||NS||NA||0.2% (7)|
|Strom, 201318||IV||367||Cervical and lumbar decompression||LMWH within 36 h||NS||3.8% (14); DVT = 2.7% (10); PE = 1.1% (4)||0|
|Thota, 20218||IV||888~ 888||Elective||Any anticoagulation|
|Clinically||0.9% (8); PE = 0.3% (3)|
1.0% (9); PE = 0.3% (3)
|2.0% (18) 0.2% (2)|
*chemoprophylaxis was defined as 5,000 U heparin, 40 mg enoxaparin, 2,500 U or 5,000 U dalteparin, or 2.5 mg fondaparinux given from 1 day prior to 3 days postoperation.
#chemoprophylaxis was defined as the following agents given between 1 day before and 3 days after surgery: 5,000 U of heparin, 40 mg of enoxaparin, 2,500 or 5,000 U of dalteparin, or 2.5mg of fondaparinux.
^ Chemoprophylaxis was defined as any of the following medications: aspirin, direct thrombin inhibitor, factor Xa inhibitors, low-molecular-weight heparin, unfractionated heparins, and warfarin.
~Propensity score-matched starting with 3,536 patients that matched a single patient who did not receive anticoagulation to a single patient who did.
All presented VTE rates are symptomatic.
n=number; VTE=Venous thromboembolism; NS=Not specified; TED=Thigh length compression; LMWH=Low-molecular-weight heparin; NA=Not available; CS=Compression stockings; US=ultrasound screening; DVT=Deep venous thrombosis; PE=Pulmonary embolism; OR=Operative room; PCS=Pneumatic compression stockings; SHE=Spinal epidural hematoma; SCH=Subcutaneous heparin.
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