Elevated pulmonary dead space and coagulation abnormalities suggest lung microvascular thrombosis in patients undergoing cardiac surgery

Intensive Care Med. 2008 Jul;34(7):1216-23. doi: 10.1007/s00134-008-1042-7. Epub 2008 Feb 27.


Objective: Inflammation has been shown to trigger microvascular thrombosis. Patients undergoing cardiac surgery sustain significant inflammatory insults to the lungs and in addition are routinely given anti-fibrinolytic agents to promote thrombosis. In view of these risk factors we investigated if evidence of pulmonary microvascular thrombosis occurs following cardiac surgery and, if so, whether a pre-operative heparin infusion may limit this.

Design: Double-blind randomised controlled trial.

Setting: Tertiary university affiliated hospital.

Patients: Twenty patients undergoing elective cardiac surgery.

Interventions: Patients were randomised to receive a pre-operative heparin infusion or placebo. All patients were administered aprotinin.

Measurements and results: Pulmonary microvascular obstruction was estimated by measuring the alveolar dead-space fraction. Pulmonary coagulation activation was estimated by measuring the ratio of prothrombin fragment levels in radial and pulmonary arterial blood. Systemic tissue plasminogen activator (t-PA) levels were also assessed. In the placebo group cardiac surgery triggered increased alveolar dead-space fraction levels and the onset of prothrombin fragment production in the pulmonary circulation. Administration of pre-operative heparin was associated with a lower alveolar dead-space fraction (p < 0.05) and reduced prothrombin fragment production in the pulmonary circulation (p < 0.05). Pre-operative heparin also increased baseline t-PA levels (p < 0.05).

Conclusion: The changes in the alveolar dead-space fraction and pulmonary coagulation activation suggest that pulmonary microvascular thrombosis develops during cardiac surgery and this may be limited by a pre-operative heparin infusion.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / administration & dosage
  • Anticoagulants / therapeutic use*
  • Aprotinin / therapeutic use*
  • Cardiopulmonary Bypass
  • Coronary Artery Bypass*
  • Double-Blind Method
  • Female
  • Hemostatics / therapeutic use*
  • Heparin / administration & dosage
  • Heparin / therapeutic use*
  • Humans
  • Inflammation / complications
  • Inflammation / etiology
  • Length of Stay
  • Lung Diseases, Obstructive / etiology*
  • Lung Diseases, Obstructive / prevention & control*
  • Male
  • Middle Aged
  • Postoperative Complications / prevention & control*
  • Preoperative Care
  • Respiratory Dead Space*
  • Thrombosis / etiology
  • Thrombosis / prevention & control*
  • Tissue Plasminogen Activator / blood


  • Anticoagulants
  • Hemostatics
  • Heparin
  • Aprotinin
  • Tissue Plasminogen Activator