Cardiopulmonary Resuscitation : Pharmacological Interventions for Augmentation of Cerebral Blood Flow

Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC). In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow. Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC. Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC. By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC. In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor