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Retrospective review.To assess the safety and efficacy of prophylactic low-molecular-weight heparin (LMWH) started 24 to 36 hours after degenerative spine surgery.Venous thromboembolism (VTE) is a significant postoperative complication best averted with dual mechanical/pharmacological prophylaxis. Pharmacological prophylaxis is widely used in patients with spinal cord injury, but there is no consensus on its role in degenerative spine surgery, particularly after laminectomy with the concurrent risk of epidural hematoma. The literature suggests a small but potentially devastating hemorrhage risk when LMWH is started within 24 hours of spine surgery. An intermediate strategy is delayed LMWH initiation to minimize hemorrhage risk and retain benefits of dual prophylaxis.Operative reports of the senior author were retrospectively reviewed for all cases of cervical and lumbar laminectomy from 2007 to 2011. Single-level decompressions without fusion and all nondegenerative cases were excluded. Baseline and operative details were recorded. Mechanical prophylaxis was used throughout admission, and prophylactic LMWH was started postoperative day 1 at 10 PM. All cases of postoperative hemorrhage (epidural hematoma, superficial hematoma, persistent wound drainage), deep venous thrombosis, and pulmonary embolism were noted.A total of 367 patients underwent multilevel laminectomy or laminectomy and fusion for degenerative disease. VTE risk factors (age >60 yr, smoking, obesity) were common. No patients receiving LMWH 24 to 36 hours after surgery developed postoperative hemorrhage (95% confidence interval: 0–0.8%). Nearly half of the study population underwent lower extremity ultrasonography or chest computed tomography, and acute VTE was diagnosed in 14 patients (3.8%; 95% confidence interval: 2.1–6.3).LMWH prophylaxis seems to carry a very low hemorrhage risk when started 24 to 36 hours after spine surgery. Larger, prospective studies are needed to assess the safety of early delayed LMWH administration more definitively. Even with aggressive prophylaxis, patients undergoing fusion or multilevel laminectomy for degenerative disease are at significant risk for VTE.