Plasminogen activator inhibitor type 1 and outcome after successful cardiopulmonary resuscitation

Objective: Patients after successful cardiopulmonary resuscitation have been shown to exhibit elevated plasma concentrations of plasminogen activator inhibitor (PAI) type 1, the main circulating antifibrinolytic protein. It has been suggested that elevations in PAI-1 contribute to cerebral no-reflow after successful cardiopulmonary resuscitation. We analyzed whether PAI-1 concentrations might predict cerebral outcome after cardiopulmonary resuscitation. Design: Prospective, controlled study. Setting: Intensive care unit at a university hospital. Patients: Thirty-five patients after successful cardiopulmonary resuscitation and 35 control patients who were not critically III. Interventions. Blood sampling for determination of plasma concentrations of active and total PAI-1 antigen. Measurements and Main Results: Plasma concentrations of total and active PAI-1 antigen on the second day after successful cardiopulmonary resuscitation were significantly higher in patients after cardiopulmonary resuscitation than in controls (p < .0001) and were unrelated to duration of cardiopulmonary resuscitation. Both active and total PAI-1 antigen were higher in patients who developed acute renal failure after cardiopulmonary resuscitation. Patients with an unfavorable cerebral outcome after cardiopulmonary resuscitation had higher total PAI-1 antigen concentrations compared with patients with good outcome after cardiopulmonary resuscitation (p = .026). We identified 180 ng/mL as the best cutoff value for total PAI-1 antigen with respect to cerebral outcome (chi-square 11.8, p = .001). In a logistic regression analysis, only systemic inflammatory response syndrome (p = .028), acute renal failure after cardiopulmonary resuscitation (p = .017), and cardiopulmonary resuscitation duration > 15 mins (p = .042) were significantly and independently associated with cerebral outcome after cardiopulmonary resuscitation. Total PAI-1 antigen reached only borderline significance (p = .058) but nevertheless slightly improved the correct prediction of cerebral outcome after cardiopulmonary resuscitation. Conclusions. Acute renal failure after cardiopulmonary resuscitation, systemic inflammatory response syndrome, and cardiopulmonary resuscitation duration are better predictors of cerebral outcome after cardiopulmonary resuscitation than PAI-1 antigen, but determination of total PAI-1 antigen nevertheless might improve the early prediction of cerebral outcome after cardiopulmonary resuscitation. Whether elevated PAI-1 concentrations, possibly via prothrombogenic/antifibrinolytic effects, contribute causally to cerebral no-reflow and acute renal failure after cardiopulmonary resuscitation remains to be clarified.