ObjectiveTo investigate the pathophysiology underlying raised lactate levels after cardiac surgery with cardiopulmonary bypass (CPB).DesignProspective observational study.SettingMedical and surgical intensive care unit of a tertiary hospital.PatientsA total of 40 patients undergoing first-time coronary artery bypass grafting with CPB.InterventionsThe prothrombotic response to cardiac surgery with CPB was assessed by measuring plasma levels of prothrombin fragment 1 + 2 and plasminogen activator inhibitor (PAI) activity. The hemodynamic responses to cardiac surgery with CPB were also measured using standard techniques.Measurements and Main ResultsAfter cardiac surgery, prothrombin fragment 1 + 2 levels increased 6-fold and PAI activity increase 2- to 3-fold (p< .0001). Lactate levels were not associated with prothrombin fragment 1 + 2 and PAI activity levels after CPB. Lactate levels were associated with baseline PAI activity (p= .006), a history of hypertension (p= .02), raised baseline lactate levels (p= .02), an early increase in body temperature after CPB (p= .05), a late increase in oxygen consumption after CPB (p= .03), and a raised white cell count after CPB (p= .06). Lactate levels were inversely associated with the maximum activated clotting time level reached during CPB (p= .02). Multivariate linear regression demonstrated lactate levels were independently associated with baseline PAI activity.ConclusionWe found cardiac surgery with CPB was associated with a marked prothrombotic response. Lactate levels were associated with elevated baseline PAI activity and evidence of an amplified inflammatory response to cardiac surgery with CPB. Our findings implicate aspects of the inflammatory response, including microvascular thrombosis, in the development of raised lactate levels after cardiac surgery with CPB.