Safety of perioperative minidose heparin in patients undergoing brain tumor surgery: a prospective, randomized, double-blind study

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Object. Thromboembolic phenomena (TEPs) continue to be a significant source of morbidity and mortality in patients undergoing neurosurgery. Although the efficacy of low-dose heparin in preventing TEPs in neurosurgical patients is well established, neurosurgeons are reluctant to use it perioperatively because of concern for increased bleeding complications. To clarify this issue, the authors used a prospective, randomized, double-blind design to evaluate the safety of minidose heparin treatment in patients undergoing surgery for supratentorial brain tumors.

Methods. One hundred three patients, all 40 years of age or older, were treated with either 5000 U of heparin (55 patients) or placebo (48 patients) starting 2 hours before surgery and continuing until full mobilization or for 7 days. Both groups were well matched for sex, weight, duration of surgery, and tumor diagnosis.

Subjective and objective parameters were used to estimate and calculate the perioperative bleeding tendency in all patients. Red blood cell mass loss was calculated by assessing the preoperative and postoperative hematocrit and the patient's weight. Intraoperative blood loss was determined by measuring the quantity of blood in the suction containers and subtracting the amount of irrigation fluids. Postoperative bleeding was measured by determining the amount of fluid in the subgaleal drain, and blood cell replacement was monitored during and after the procedure. Intracranial bleeding was graded according to findings on the postoperative computerized tomography scan obtained 48 to 72 hours after surgery. In addition, the senior surgeon in each case was asked to assess each patient's bleeding tendency during the operation. The results showed that perioperative administration of heparin did not significantly alter bleeding tendency by any measured parameter. The surgeon was blinded to which group individual patients had been allocated.

Conclusions. Perioperative minidose heparin is safe for use in patients undergoing craniotomy for supratentorial tumors. This relatively simple and inexpensive measure is recommended as a routine regimen for the prevention of TEPs in patients undergoing neurosurgery.

Article Information

Contributor Notes

Address reprint requests to: Shlomi Constantini, M.D., M.Sc., Division of Pediatric Neurosurgery, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. email: sconsts@netvision.net.il.

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References
  • 1.

    Agnelli GPiovella FBuoncristiani Pet al: Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 339:80851998Agnelli G Piovella F Buoncristiani P et al: Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 339:80–85 1998

    • Search Google Scholar
    • Export Citation
  • 2.

    Agu OHamilton GBaker D: Graduated compression stockings in the prevention of venous thromboembolism. Br J Surg 86:99210041999Agu O Hamilton G Baker D: Graduated compression stockings in the prevention of venous thromboembolism. Br J Surg 86:992–1004 1999

    • Search Google Scholar
    • Export Citation
  • 3.

    Barnett HGClifford JRLlewellyn RC: Safety of mini-dose heparin administration for neurosurgical patients. J Neurosurg 47:27301977Barnett HG Clifford JR Llewellyn RC: Safety of mini-dose heparin administration for neurosurgical patients. J Neurosurg 47:27–30 1977

    • Search Google Scholar
    • Export Citation
  • 4.

    Boström SHolmgren EJonsson Oet al: Post-operative thromboembolism in neurosurgery. A study on the prophylactic effect of calf muscle stimulation plus dextran compared to low-dose heparin. Acta Neurochir 80:83891986Boström S Holmgren E Jonsson O et al: Post-operative thromboembolism in neurosurgery. A study on the prophylactic effect of calf muscle stimulation plus dextran compared to low-dose heparin. Acta Neurochir 80:83–89 1986

    • Search Google Scholar
    • Export Citation
  • 5.

    Cerrato DAriano CFiacchino F: Deep vein thrombosis and low-dose heparin prophylaxis in neurosurgical patients. J Neurosurg 49:3783811978Cerrato D Ariano C Fiacchino F: Deep vein thrombosis and low-dose heparin prophylaxis in neurosurgical patients. J Neurosurg 49:378–381 1978

    • Search Google Scholar
    • Export Citation
  • 6.

    Chan ATAtiemo ADiran LKet al: Venous thromboembolism occurs frequently in patients undergoing brain tumor surgery despite prophylaxis. J Thromb Thrombolysis 8:1381421999Chan AT Atiemo A Diran LK et al: Venous thromboembolism occurs frequently in patients undergoing brain tumor surgery despite prophylaxis. J Thromb Thrombolysis 8:138–142 1999

    • Search Google Scholar
    • Export Citation
  • 7.

    Cheruku RTapazoglou EEnsley Jet al: The incidence and significance of thromboembolic complications in patients with high-grade gliomas. Cancer 68:262126241991Cheruku R Tapazoglou E Ensley J et al: The incidence and significance of thromboembolic complications in patients with high-grade gliomas. Cancer 68:2621–2624 1991

    • Search Google Scholar
    • Export Citation
  • 8.

    Choucair AKSilver PLevin VA: Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism. J Neurosurg 66:3573581987Choucair AK Silver P Levin VA: Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism. J Neurosurg 66:357–358 1987

    • Search Google Scholar
    • Export Citation
  • 9.

    Constantini SKornowski RPomeranz Set al: Thromboembolic phenomena in neurosurgical patients operated upon for primary and metastatic brain tumours. Acta Neurochir 109:93971991Constantini S Kornowski R Pomeranz S et al: Thromboembolic phenomena in neurosurgical patients operated upon for primary and metastatic brain tumours. Acta Neurochir 109:93–97 1991

    • Search Google Scholar
    • Export Citation
  • 10.

    Dickinson LDMiller LDPatel CPet al: Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors. Neurosurgery 43:107410811998Dickinson LD Miller LD Patel CP et al: Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors. Neurosurgery 43:1074–1081 1998

    • Search Google Scholar
    • Export Citation
  • 11.

    Frim DMBarker FG IIPoletti CEet al: Postoperative low-dose heparin decreases thromboembolic complications in neurosurgical patients. Neurosurgery 30:8308331992Frim DM Barker FG II Poletti CE et al: Postoperative low-dose heparin decreases thromboembolic complications in neurosurgical patients. Neurosurgery 30:830–833 1992

    • Search Google Scholar
    • Export Citation
  • 12.

    Hamilton MGHull RDPineo GF: Venous thromboembolism in neurosurgery and neurology patients: a review. Neurosurgery 34:2802961994Hamilton MG Hull RD Pineo GF: Venous thromboembolism in neurosurgery and neurology patients: a review. Neurosurgery 34:280–296 1994

    • Search Google Scholar
    • Export Citation
  • 13.

    Hatton JLu WYRhoney DHet al: A step-wise protocol for stress ulcer prophylaxis in the neurosurgical intensive care unit. Surg Neurol 46:4934991996Hatton J Lu WY Rhoney DH et al: A step-wise protocol for stress ulcer prophylaxis in the neurosurgical intensive care unit. Surg Neurol 46:493–499 1996

    • Search Google Scholar
    • Export Citation
  • 14.

    Inci SErbengi ABerker M: Pulmonary embolism in neurosurgical patients. Surg Neurol 43:1231291995Inci S Erbengi A Berker M: Pulmonary embolism in neurosurgical patients. Surg Neurol 43:123–129 1995

    • Search Google Scholar
    • Export Citation
  • 15.

    Kakkar VV: Low molecular weight heparins: prophylaxis of venous thromboembolism in surgical patients. Semin Hematol 34 (Suppl 4):9191997Kakkar VV: Low molecular weight heparins: prophylaxis of venous thromboembolism in surgical patients. Semin Hematol 34 (Suppl 4):9–19 1997

    • Search Google Scholar
    • Export Citation
  • 16.

    Kakkar VVBoeckl OBoneu Bet al: Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial. World J Surg 21:291997Kakkar VV Boeckl O Boneu B et al: Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial. World J Surg 21:2–9 1997

    • Search Google Scholar
    • Export Citation
  • 17.

    Levin JMSchiff DLoeffler JSet al: Complications of therapy for venous thromboembolic disease in patients with brain tumors. Neurology 43:111111141993Levin JM Schiff D Loeffler JS et al: Complications of therapy for venous thromboembolic disease in patients with brain tumors. Neurology 43:1111–1114 1993

    • Search Google Scholar
    • Export Citation
  • 18.

    Levine MNGent MHirsh Jet al: Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery. Arch Intern Med 156:8518561996Levine MN Gent M Hirsh J et al: Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery. Arch Intern Med 156:851–856 1996

    • Search Google Scholar
    • Export Citation
  • 19.

    Lu WYRhoney DHBoling WBet al: A review of stress ulcer prophylaxis in the neurosurgical intensive care unit. Neurosurgery 41:4164261997Lu WY Rhoney DH Boling WB et al: A review of stress ulcer prophylaxis in the neurosurgical intensive care unit. Neurosurgery 41:416–426 1997

    • Search Google Scholar
    • Export Citation
  • 20.

    Macdonald RLAmidei CLin Get al: Safety of perioperative subcutaneous heparin for prophylaxis of venous thromboembolism in patients undergoing craniotomy. Neurosurgery 45:2452521999Macdonald RL Amidei C Lin G et al: Safety of perioperative subcutaneous heparin for prophylaxis of venous thromboembolism in patients undergoing craniotomy. Neurosurgery 45:245–252 1999

    • Search Google Scholar
    • Export Citation
  • 21.

    Nurmohamed MTvan Riel AMHenkens CMAet al: Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery. Thromb Haemost 75:2332381996Nurmohamed MT van Riel AM Henkens CMA et al: Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery. Thromb Haemost 75:233–238 1996

    • Search Google Scholar
    • Export Citation
  • 22.

    Nurmohamed MTVerhaeghe RHaas Set al: A comparative trial of a low molecular weight heparin (enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. Am J Surg 169:5675711995Nurmohamed MT Verhaeghe R Haas S et al: A comparative trial of a low molecular weight heparin (enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. Am J Surg 169:567–571 1995

    • Search Google Scholar
    • Export Citation
  • 23.

    Quevedo JFBuckner JCSchmidt JLet al: Thromboembolism in patients with high-grade glioma. Mayo Clin Proc 69:3293321994Quevedo JF Buckner JC Schmidt JL et al: Thromboembolism in patients with high-grade glioma. Mayo Clin Proc 69:329–332 1994

    • Search Google Scholar
    • Export Citation
  • 24.

    Sawaya RKornblith PL: Brain tumors and thromboembolic complications. Surg Neurol 28:1631987Sawaya R Kornblith PL: Brain tumors and thromboembolic complications. Surg Neurol 28:163 1987

    • Search Google Scholar
    • Export Citation
  • 25.

    Schiff DDeAngelis LM: Therapy of venous thromboembolism in patients with brain metastases. Cancer 73:4934981994Schiff D DeAngelis LM: Therapy of venous thromboembolism in patients with brain metastases. Cancer 73:493–498 1994

    • Search Google Scholar
    • Export Citation
  • 26.

    Stephens PHHealy MTSmith Met al: Prophylaxis against thromboembolism in neurosurgical patients: a survey of current practice in the United Kingdom. Br J Neurosurg 9:1591631995Stephens PH Healy MT Smith M et al: Prophylaxis against thromboembolism in neurosurgical patients: a survey of current practice in the United Kingdom. Br J Neurosurg 9:159–163 1995

    • Search Google Scholar
    • Export Citation
  • 27.

    Swann KWBlack PM: Deep vein thrombosis and pulmonary emboli in neurosurgical patients: a review. J Neurosurg 61:105510621984Swann KW Black PM: Deep vein thrombosis and pulmonary emboli in neurosurgical patients: a review. J Neurosurg 61:1055–1062 1984

    • Search Google Scholar
    • Export Citation
  • 28.

    Valladares JBHankinson J: Incidence of lower extremity deep vein thrombosis in neurosurgical patients. Neurosurgery 6:1381411980Valladares JB Hankinson J: Incidence of lower extremity deep vein thrombosis in neurosurgical patients. Neurosurgery 6:138–141 1980

    • Search Google Scholar
    • Export Citation
  • 29.

    Wen DYHall WA: Complications of subcutaneous low-dose heparin therapy in neurosurgical patients. Surg Neurol 50:5215251998Wen DY Hall WA: Complications of subcutaneous low-dose heparin therapy in neurosurgical patients. Surg Neurol 50:521–525 1998

    • Search Google Scholar
    • Export Citation
  • 30.

    Zelikovski AZucker GEliashiv Aet al: A new sequential pneumatic device for the prevention of deep vein thrombosis. J Neurosurg 54:6526541981Zelikovski A Zucker G Eliashiv A et al: A new sequential pneumatic device for the prevention of deep vein thrombosis. J Neurosurg 54:652–654 1981

    • Search Google Scholar
    • Export Citation
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