Objective: There is growing evidence that therapeutic hypothermia and other post-resuscitation care improves outcomes in out-of-hospital cardiac arrest (OHCA). Thus, transporting patients with return of spontaneous circulation (ROSC) to specialized facilities may increase survival rates. However, it is unknown whether prolonging transport to reach a designated facility would be detrimental. Methods: Data from OHCA patients treated in EMS systems that cover approximately 70% of Arizona's population were evaluated (October 2004-December 2006). We analyzed the association between transport interval (depart scene to ED arrival) and survival to hospital discharge in adult, non-traumatic OHCA patients and in the subgroup who achieved ROSC and remained comatose. Results: 1846 OHCA occurred prior to EMS arrival. Complete transport interval data were available for 1177 (63.8%) patients (study group). 253 patients (21.5%) achieved ROSC and remained comatose making them theoretically eligible for transport to specialized care. Overall, 70 patients (5.9%) survived and 43 (17.0%) comatose ROSC patients survived. Mean transport interval for the study group was 6.9 min (95% CI: 6.7, 7.1). Logistic regression revealed factors that were independently associated with survival: witnessed arrest, bystander CPR, method of CPR, initial rhythm of ventricular fibrillation, and shorter EMS response time interval. There was no significant association between transport interval and outcome in either the overall study group (OR = 1.2; 0.77, 1.8) or in the comatose, ROSC subgroup (OR 0.94; 0.51, 1.8). Conclusion: Survival was not significantly impacted by transport interval. This suggests that a modest increase in transport interval from bypassing the closest hospital en route to specialized care is safe and warrants further investigation.

<p>Ischemic neuronal injury continues to be a major delimiting factor in achieving successful clinical outcomesafter resuscitation from cardiac arrest. In this thesis, a pig model of cardiopulmonary resuscitation (CPR) wasused to address the effects of different interventions on cerebral blood flow and oxygenation during CPR and theinitial postresuscitation period. A novel technique is presented to quantify the reperfusion oxidative injury.</p><p>Maximization of cerebral blood flow during CPR by open-chest cardiac compression, continuous aortic balloon occlusion, and intra-aortic administration of hypertonic saline-dextran (HSD) did not ameliorate thepostresuscitation hypoperfusion or improve the cerebral oxygen extraction ratio or tissue pH. These findings disaffirm earlier studies suggesting that conserving brain viability after global ischemia is mostly a question ofmaintaining high perfusion pressure.</p><p>Despite an increased cerebral perfusion pressure during CPR, intra-aortic administered epinephrineabove the aortic balloon occlusion did not further improve cerebral blood flow and oxygenation. This findingmay indicate adverse effects of epinephrine on cerebral vascular beds, possibly induced by a relatively highconcentration of epinephrine when administered above the site for aortic balloon occlusion.</p><p>The IV administration of equipotent doses of epinephrine or vasopressin during CPR resulted incomparable hemodynamic changes. The peak increase in cerebral cortical blood flow, however, was reachedapproximately 30 sec later by vasopressin. Furthermore, the second bolus of vasopressin during CPR did notaugment cerebral perfusion, whereas epinephrine did. Consequently, reports suggesting that vasopressin issuperior to epinephrine with respect to its effects on central hemodynamics and vital organ blood flow may bebiased by the pharmacodynamic differences between the drugs, depending on the time point at which blood flowmeasurements are performed.</p><p>In comparison with IV vasopressin, vasopressin administered above the aortic balloon occlusion resulted in a significant increase in cerebral perfusion pressure during CPR, but not after restoration of spontaneous circulation (ROSC). Cerebral cortical blood flow was, however, not improved <i>during</i> CPR, whereas a significant increase was recorded <i>after</i> ROSC. Relatively higher concentrations of vasopressin above the sitefor intra-aortic balloon occlusion may, therefore, predominantly induce cerebral cortical vasoconstriction duringCPR but induce vasodilatation after ROSC.</p><p>Assessment of oxidative stress or inflammation have been extremely difficult to attain. In our pig model of resuscitation, an association wasobserved between the duration of cardiac arrest and jugular bulb levels of 8-iso-PGF_2α, a major isoprostane and a novel index of oxidative injury. 8-iso-PGF_2α, and the prostaglandin 15-K-DH-PGF_2α, increased within 5 min after ROSC and remained so up to 2 h, indicating the interval of time during which cerebral reperfusion oxidative injury and inflammatory response may occur and are potentially preventable.</p>

Ischemic neuronal injury continues to be a major delimiting factor in achieving successful clinical outcomesafter resuscitation from cardiac arrest. In this thesis, a pig model of cardiopulmonary resuscitation (CPR) wasused to address the effects of different interventions on cerebral blood flow and oxygenation during CPR and theinitial postresuscitation period. A novel technique is presented to quantify the reperfusion oxidative injury. Maximization of cerebral blood flow during CPR by open-chest cardiac compression, continuous aortic balloon occlusion, and intra-aortic administration of hypertonic saline-dextran (HSD) did not ameliorate thepostresuscitation hypoperfusion or improve the cerebral oxygen extraction ratio or tissue pH. These findings disaffirm earlier studies suggesting that conserving brain viability after global ischemia is mostly a question ofmaintaining high perfusion pressure. Despite an increased cerebral perfusion pressure during CPR, intra-aortic administered epinephrineabove the aortic balloon occlusion did not further improve cerebral blood flow and oxygenation. This findingmay indicate adverse effects of epinephrine on cerebral vascular beds, possibly induced by a relatively highconcentration of epinephrine when administered above the site for aortic balloon occlusion. The IV administration of equipotent doses of epinephrine or vasopressin during CPR resulted incomparable hemodynamic changes. The peak increase in cerebral cortical blood flow, however, was reachedapproximately 30 sec later by vasopressin. Furthermore, the second bolus of vasopressin during CPR did notaugment cerebral perfusion, whereas epinephrine did. Consequently, reports suggesting that vasopressin issuperior to epinephrine with respect to its effects on central hemodynamics and vital organ blood flow may bebiased by the pharmacodynamic differences between the drugs, depending on the time point at which blood flowmeasurements are performed. In comparison with IV vasopressin, vasopressin administered above the aortic balloon occlusion resulted in a significant increase in cerebral perfusion pressure during CPR, but not after restoration of spontaneous circulation (ROSC). Cerebral cortical blood flow was, however, not improved during CPR, whereas a significant increase was recorded after ROSC. Relatively higher concentrations of vasopressin above the sitefor intra-aortic balloon occlusion may, therefore, predominantly induce cerebral cortical vasoconstriction duringCPR but induce vasodilatation after ROSC. Assessment of oxidative stress or inflammation have been extremely difficult to attain. In our pig model of resuscitation, an association wasobserved between the duration of cardiac arrest and jugular bulb levels of 8-iso-PGF2α, a major isoprostane and a novel index of oxidative injury. 8-iso-PGF2α, and the prostaglandin 15-K-DH-PGF2α, increased within 5 min after ROSC and remained so up to 2 h, indicating the interval of time during which cerebral reperfusion oxidative injury and inflammatory response may occur and are potentially preventable.

<p>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).</p><p>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.</p><p>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.</p><p>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.</p><p>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. </p><p>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. </p>

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.