Oliver J. Liakopoulos

Successful resuscitation after prolonged periods of cardiac arrest: A new field in cardiac surgery

OBJECTIVE Cardiopulmonary resuscitation is associated with high mortality and poor neurological recovery. Cardiopulmonary resuscitation can cause ischemia-reperfusion injury of the whole body and brain. We assessed the hypothesis that controlled reperfusion of the whole body with cardiopulmonary bypass would limit reperfusion injury after 15 minutes of normothermic cardiac arrest with better survival and neurological recovery. METHODS Eleven pigs were exposed to normothermic ischemia for 15 minutes by inducing ventricular fibrillation, followed by cardiopulmonary resuscitation (control group, n = 4) or 60 minutes of cardiopulmonary bypass (treatment group, n = 7). Conditions of reperfusion and the reperfusate were controlled with cardiopulmonary bypass. Animals were observed for up to 7 days, and neurological assessment (Neurological Deficit Score: 0, normal; 500, brain death), magnetic resonance imaging, and brain histology were performed. RESULTS All animals in the control group died after 20 minutes of cardiopulmonary resuscitation (n = 4). All (n = 7) survived in the treatment group. Clinically apparent neurological recovery occurred within 24 hours; 1 fully conscious pig could not walk. The Neurological Deficit Score was 98 +/- 31 in all animals (n = 7) after 24 hours and decreased to 0 after 48 hours in 4 of 5 eligible animals; 1 animal had a Neurological Deficit Score of 110 after 3 days. Brain histology revealed hypoxic and apoptotic neurons with an inconclusive correlation regarding neurological recovery. CONCLUSION Clinically apparent neurological recovery after a period of 15 minutes of cardiac arrest occurred with cardiopulmonary bypass instead of cardiopulmonary resuscitation for reperfusing the whole body. This approach contrasts with cardiopulmonary resuscitation, in which resuscitation has been reported as successful after only 3 to 5 minutes of cardiac arrest. Cardiopulmonary bypass might be a key to improve survival and neurological recovery after cardiac arrest.

Resuscitation After Prolonged Cardiac Arrest: Role of Cardiopulmonary Bypass and Systemic Hyperkalemia

BACKGROUND The purpose of this study was to determine (1) the role of emergency cardiopulmonary bypass (CPB) after prolonged cardiac arrest and failed cardiopulmonary resuscitation, and (2) the use of systemic hyperkalemia during CPB to convert intractable ventricular fibrillation (VF). METHODS Thirty-one pigs (34 +/- 2 kg) underwent 15 minutes of cardiac arrest after induced VF, followed by 10 minutes of cardiopulmonary resuscitation-advanced life support. Peripheral CPB was used if cardiopulmonary resuscitation failed to restore stable circulation. Damage was assessed by evaluating hemodynamics, biochemical variables (creatine kinase-MB, neuron-specific enolase), neurologic deficit score, and brain magnetic resonance imaging. RESULTS Cardiopulmonary resuscitation alone was successful in only 19% (6 of 31 pigs). Cardiopulmonary bypass was initiated in 81% of animals (25 of 31 pigs) either for hypotension (5 of 25 pigs) or intractable VF (20 of 25 pigs). Defibrillation was successful in 7 of 20 animals during the first 10 minutes after initiating CPB. Ventricular fibrillation persisted more than 10 minutes in 13 of 20 pigs, and animals were treated either with repeated defibrillation (6 of 13 pigs) or with a potassium bolus (7 of 13 pigs) to induce transient cardiac arrest. Overall survival at 24 hours was 84% with cardiopulmonary resuscitation (100% of pigs with hypotension; 71% in CPB-VF < 10 minutes). Despite CPB, fatal myocardial failure occurred after VF duration of more than 10 minutes in all pigs treated with electrical defibrillation, whereas hyperkalemia allowed 100% cardioversion and 86% survival. Biochemical variables remained elevated in all groups. Similarly, severe brain injury was present in all animals as confirmed by neurologic deficit score (197 +/- 10) and magnetic resonance imaging. CONCLUSIONS Emergency CPB after prolonged cardiac arrest improves survival and allows systemic hyperkalemia to convert intractable VF, but fails to reduce neurologic damage.

An experimental and clinical evaluation of a novel central venous catheter with integrated oximetry for pediatric patients undergoing cardiac surgery.

BACKGROUND:Central venous oxygen saturation (ScvO2) accurately reflects cardiocirculatory function, but is not always feasible in pediatric patients. Using an experimental and clinical approach, we determined the accuracy of a novel pediatric central venous catheter with integrated fiberoptic oximetry, correlated ScvO2 to periprocedural vital variables, and tested its feasibility in pediatric cardiac surgery patients. METHODS:In five anesthetized pigs, hemodynamics (cardiac index [CI], heart rate; mean arterial blood [MAP]; mean pulmonary artery [MPAP], central venous pressure [CVP]), fiberoptic ScvO2 (ScvO2-cath), and blood gas oximetry (ScvO2-blood) were measured during stable baseline conditions, preload reduction (caval occlusion), and dopamine infusion (5 mcg · kg−1 · min−1). In 16 pediatric patients undergoing cardiac surgery (median age 8.4 mo; weight 8.0 kg), central venous oximetry catheters were placed percutaneously, and ScvO2-cath and hemodynamics recorded at several time-points during and until 24 h after surgery. Oximetry and hemodynamic data were compared by correlation (Pr) and the Bland–Altman analysis. RESULTS:There were no catheter-related complications. ScvO2-cath and ScvO2-blood measurements correlated significantly (P < 0.001) in both the experimental (Pr = 0.96) and clinical protocol (Pr = 0.94). A similar bias and precision over all time-points was detected in both protocols (Exp-bias: +0.03% ± 4.11%; Clinical-bias: −0.03% ± 4.41%). ScvO2-cath correlated (P < 0.001) with CI (Pr = 0.87), MAP (Pr = 0.59), MPAP (Pr = 0.44), and CVP (Pr = 0.38) and estimated CI better than MAP (Pr = 0.61), MPAP (Pr = 0.38), CVP (Pr = 0.35), or heart rate (Pr = 0.25). CONCLUSION:Integrated central venous oximetry catheters provide accurate continuous ScvO2 monitoring in pediatric patients undergoing cardiac surgery. ScvO2 fiberoptic oximetry correlates better with changes in CI as compared to routine hemodynamic variables.

Right Ventricular Failure Resulting from Pressure Overload: Role of Intra-Aortic Balloon Counterpulsation and Vasopressor Therapy

BACKGROUND Augmentation of coronary perfusion may improve right ventricular (RV) failure following acute increases of RV afterload. We investigated whether intra-aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing myocardial perfusion and reversing compromised biventricular interactions using a model of acute pressure overload. MATERIALS AND METHODS In 10 anesthetized pigs, RV failure was induced by pulmonary artery constriction and systemic hypertension strategies with IABP, phenylephrine (PE), or the combination of both were tested. Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures, coronary driving pressures (CDP)] were measured and echocardiography was used to assess tricuspid valve regurgitation, septal positioning (eccentricity index (ECI)), and changes in ventricular and septal dimensions and function [myocardial performance index (MPI), peak longitudinal strain]. RESULTS Pulmonary artery constriction resulted in doubling of RV systolic pressure (54 ± 4mm Hg), RV distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%), septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (-30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05). With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further augmented (+25%). IABP resulted in LV unloading and restored LV function, and increased CI (+46%) and SvO(2) (+29%; P<0.05). CONCLUSIONS IABP with minimal vasopressors augments myocardial perfusion pressure and optimizes RV function after pressure-induced failure.

Superior neurologic recovery after 15 minutes of normothermic cardiac arrest using an extracorporeal life support system for optimized blood pressure and flow

Objective: Sudden cardiac arrest is one of the leading causes of death. Conventional CPR techniques after cardiac arrest provide circulation with reduced and varying blood flow and pressure. We hypothesize that using pressure- and flow-controlled reperfusion of the whole body improves neurological recovery and survival after 15 min of normothermic cardiac arrest. Methods: Pigs were randomized in two experimental groups and exposed to 15 min of ventricular fibrillation (VF). After this period, the animals in the control group received conventional CPR with open chest compression (n=6), while circulation in the treatment group (n=6) was established with an extracorporeal life support system (ECLS) to control blood pressure and flow. Follow-up included the assessment of neurological recovery and magnetic resonance imaging (MRI) for up to 7 days. Results: Five of the six animals in the control group died, one animal was resuscitated successfully. In the treatment group, 1/6 could not be separated from ECLS. Five out of the six pigs survived and were transferred to the animal facility. One animal was unable to walk and had to be sacrificed 30 hours after ECLS. The remaining 4 animals of the treatment group and the surviving pig from the control group showed complete neurological recovery. Brain MRI revealed no pathological changes. Conclusion: We were able to demonstrate a significant improvement in survival after 15 minutes of normothermic cardiac arrest. These results support our hypothesis that using an ECLS for pressure- and flow-controlled circulation after circulatory arrest is superior to conventional CPR.

In vivo detection of myocardial ischemia in pigs using visible light spectroscopy.

BACKGROUND: Monitoring tissue oxygenation (StO2) by visible light spectroscopy (VLS) can identify tissue ischemia, but its feasibility for detecting myocardial ischemia is not known. We hypothesized that VLS can reliably detect changes in myocardial StO2 in pigs subjected to acute regional or global myocardial ischemia. METHODS: In 11 pigs, regional myocardial ischemia was created by ligation of left anterior descending artery (LAD). Myocardial StO2 was determined from the ischemic and nonischemic left ventricular (LV) regions and compared to coronary venous saturations. Myocardial function was assessed by echocardiography. In six pigs, LV-StO2 was measured during cardiopulmonary bypass (CPB), after cardioplegic cardiac arrest, and during CPB with inadequate myocardial protection. Additionally, right ventricular (RV)- and LV-StO2 were assessed during acute RV pressure overload from pulmonary artery (PA) banding. RESULTS: StO2 baselines in pigs undergoing LAD occlusion were similar in the ischemic and nonischemic myocardium (70% ± 8% vs 74% ± 5%). After LAD ligation, StO2 rapidly declined (30 s: 59% ± 8%; 1 min:50 ± 9; 5 min:42% ± 4%; P < 0.05) in the ischemic myocardium. Decreases in StO2 correlated with coronary venous saturations (r = 0.88) and were associated with myocardial dysfunction. In pigs undergoing CPB, LV-StO2 remained unchanged with initiation of CPB or after cardioplegic cardiac arrest, but LV ischemia was detected by StO2 after aortic cross-clamp without adequate myocardial protection. Similarly, PA banding resulted in a profound decrease of RV-StO2 from 69% ± 6% to 52% ± 7% (P < 0.05) with recovery after PA release. CONCLUSIONS: VLS is a reliable method of detecting alterations in myocardial StO2 and can be a useful monitor for rapid identification of myocardial ischemia.

Resuscitation after prolonged cardiac arrest: effects of cardiopulmonary bypass and sodium–hydrogen exchange inhibition on myocardial and neurological recovery

OBJECTIVE To determine if cardiopulmonary bypass (CPB), together with inhibition of the sodium-hydrogen exchanger (NHE), limits myocardial and neurological injury and improves recovery after prolonged (unwitnessed) cardiac arrest (CA), as NHE inhibition improved recovery after deep hypothermic circulatory arrest. METHODS Twenty-seven pigs (31-39 kg) underwent 15 min of prolonged (no-flow) CA followed by 10 min of cardiopulmonary resuscitation-advanced life support (CPR-ALS). Subjects with restoration of spontaneous circulation (ROSC) during CPR-ALS received either no drug (n=6) or an inhibitor of the NHE (HOE-642; n=5). In the 16 unsuccessfully resuscitated animals, peripheral normothermic CPB was instituted, and either no drug (n=9) or similar HOE-642 (n=7) therapy started. Hemodynamic data, a species-specific neurological deficit score (0=normal to 500=brain death), and mortality were recorded at 24h, and biochemical variables of organ injury measured. RESULTS CPR-ALS restored ROSC in 41% (11/27) of animals, but was unsuccessful in 59% (16/27) that required CPB. Without CPB, HOE-642 increased cardiac index and decreased vascular resistance; with CPB, HOE-642 caused higher pump flows (3.4±0.6 l min(-1)m(-2) vs 2.5±0.7 l min(-1)m(-2); p<0.001) and higher post-arrest cardiac index; but animals required more vasopressors (p=0.019) from drug-induced vasodilation. No differences between biochemical markers of oxidative and organ injury and overall 24-h mortality (20%) were found between groups. Neurological score was improved at 24h compared with 4h only after HOE-642 treatment with (150±34 vs 220±43; p=0.003) or without CPB (162±39 vs 238±48; p≤0.001), but failed to reach statistical difference with respect to the untreated group. CONCLUSIONS CPB is an effective resuscitative tool to treat prolonged CA but there is limited improvement of neurological function. NHE inhibition augments cardiac and neurological function, but its effect was less pronounced than in other studies.