Introduction: Guidelines for treatment of cardiac arrest recommend minimizing interruptions in chest compressions based on research indicating that interruptions compromise coronary perfusion pressure (CPP) and blood flow and reducing the likelihood of successful defibrillation. We investigated the dynamics of CPP before, during, and after compression interruptions and how they change over time. Methods: CPR was performed on domestic swine (~30 Kg) using standard physiological monitoring. Blood flow was measured in the abdominal aorta (AAo), the inferior vena cava, the right common carotid and external jugular. Ventricular fibrillation (VF) was electrically induced. Mechanical chest compressions (CC) were started after four minutes of VF. CC were delivered at a rate of 100 compressions per minute (cpm) and at a depth of 2” for a total of 12 min. CPP was calculated as the difference between aortic and right atrial pressure at end-diastole per Utstein guidelines. CPP was determined for 5 compressions prior to the interruption, every 2 seconds during the CC interruption, and for 7 compressions after the interruption. Per protocol, 12 interruptions occurred at randomized time points. Results: Across 12 minutes of CPR, averaged CPP prior to interruption was significantly greater than the averaged CPP after the interruption (22.4±1.0 vs. 15.5±0.73 mmHg). As CPR continued throughout the 12 minutes, CPP during compressions decreased (First 6 min = 24.1±1.4 vs. Last 6 min = 20.1±1.3 mmHg, p=0.05), but the effect of interruptions remained constant resulting in a 20% drop in CPP for every 2 seconds irrespective of the prior CPP. The increase (slope) of CPP after resumption of compressions was significantly reduced over time (First 6 min = 1.47±0.18 vs. Last 6 min = 0.82±0.13 mmHg/compression). Conclusions: Chest compression interruptions have a detrimental effect on coronary perfusion and blood flow. The magnitude of this effect increases over time as a resuscitation effort continues. These data confirm the importance of providing uninterrupted CPR particularly in long duration resuscitations.
Introduction: Cardiac power is a strong predictor of mortality in a variety of critical conditions. Measurements of cerebral oxygenation (rSO2) may be a useful non-invasive monitoring tool. However, the physiology underlying changes in rSO2 during critical states such as hemorrhage is not completely understood. This analysis examined the effect of blood pressure, flow, and cardiac power on rSO2. Methods: Eight swine underwent a pressure-targeted hemorrhage protocol. Animals were instrumented with ultrasonic flow probes on a carotid and pulmonary artery and a jugular vein. Invasive pressure catheters were placed in the aorta and right atrium. rSO2 was measured using a tissue oximeter. Arterial blood was removed at a rate of 20 mL/min to a target diastolic pressure of 35 mmHg. Baseline airway pressure of 15 cm H2O was applied up to three times during the hemorrhage to introduce transient periods of decreased cardiac output. The aortic pressure waveform was used to identify individual heartbeats. Blood pressures and flows were measured for each heartbeat in mmHg and ml/min, respectively. Cardiac power was calculated as the product of blood pressure and flow. Cardiac power, peak systolic aortic pressure, and carotid blood flow were entered into univariate regression models to predict rSO2. Results: A total of 53,314 heartbeats were identified in the 8 animals. Mean systolic aortic pressure at baseline was 85±12 mmHg and reduced to 44±11 mmHg later into the hemorrhage. Baseline mean cardiac power was 0.15±0.08 W and reduced to 0.04±0.03 W, 40±7 min from start of bleed. Cardiac power, peak systolic aortic pressure, and carotid blood flow were all predictors of rSO2 [p< 0.05]. Cardiac power was the strongest predictor, explaining 85% of the variance in the rSO2 data, with peak systolic aortic pressure explaining 77%, and carotid blood flow explaining 83%. Conclusions: Cardiac power, peak systolic aortic pressure, and carotid blood flow are all significant predictors of rSO2 values with cardiac power explaining slightly more of the variance in rSO2 data. This highlights that composite measures of hemodynamics including both pressure and flow are better correlates of rSO2 than pressure and flow independently in this animal model of hemorrhagic shock.
It is not yet clear whether hemofiltration can reduce blood cytokine levels sufficiently to benefit patients who suffer prolonged cardiac arrest (CA) treated with cardiopulmonary bypass (CPB). We sought to assess effects of high-volume and standard volume continuous veno-venous hemofiltration (CVVH) on blood cytokine levels and survival in a rat model of prolonged CA treated with CPB.Sprague-Dawley male rats were subjected to 12 min of asphyxia to induce CA. CPB was initiated for resuscitation of animals and maintained for 30 min. Twenty-four rats were randomly assigned into three groups: without CVVH treatment (sham); standard volume CVVH at a filtration rate of 35-45 mL/kg/h; and high-volume hemofiltration (HVHF, 105-135 mL/kg/h). Hemofiltration was started simultaneously with CPB and maintained for 6 h. Plasma TNFα and IL-6 levels were measured at baseline, 0.5, 1, 2, 3, and 6 h after reperfusion. Survival time, neurological deficit score, and hemodynamic status were assessed.All animals survived over 6 h and died within 24 h. There were no significant differences in survival time (log-rank test, sham vs. CVVH; p = 0.49, sham vs. HVHF; p = 0.33) or neurological deficit scores (ANOVA, p = 0.14) between the groups. There were no significant differences in blood cytokine levels between the groups. Mean blood pressure in sham group animals increased to 1.5-fold higher than baseline levels at 30 min. HVHF significantly reduced blood pressure to 0.7-fold of sham group (p < 0.01).There was no improvement in mortality, neurological dysfunction, TNFα, or IL-6 levels in rats after prolonged CA with CPB on either hemofiltration group when compared to the sham group.
Abstract Using a new method for measuring the molecular ratio (R) of inhalation to exhalation, we investigated the effect of high fraction of inspired oxygen (FIO2) on oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ) in mechanically ventilated rats. Twelve rats were equally assigned into two groups by anesthetics: intravenous midazolam/fentanyl vs. inhaled isoflurane. R, VO2, VCO2, and RQ were measured at FIO2 0.3 or 1.0. R error was ± 0.003. R was 1.0099 ± 0.0023 with isoflurane and 1.0074 ± 0.0018 with midazolam/fentanyl. R was 1.0081 ± 0.0017 at an FIO2 of 0.3 and 1.0092 ± 0.0029 at an FIO2 of 1.0. There were no differences in VCO2 among the groups. VO2 increased at FIO2 1.0, which was more notable when midazolam/fentanyl was used (isoflurane-FIO2 0.3: 15.4 ± 1.1; isoflurane-FIO2 1.0: 17.2 ± 1.8; midazolam/fentanyl-FIO2 0.3: 15.4 ± 1.1; midazolam/fentanyl-FIO2 1.0: 21.0 ± 2.2 mL/kg/min at STP). The RQ was lower at FIO2 1.0 than FIO2 0.3 (isoflurane-FIO2 0.3: 0.80 ± 0.07; isoflurane-FIO2 1.0: 0.71 ± 0.05; midazolam/fentanyl-FIO2 0.3: 0.79 ± 0.03; midazolam/fentanyl-FIO2 1.0: 0.59 ± 0.04). R was not affected by either anesthetics or FIO2. Inspired 100% O2 increased VO2 and decreased RQ, which might be more remarkable when midazolam/fentanyl was used.
Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival.To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF).After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure-targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival.The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9-13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0-12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0-3] vs. 2 [range, 2-2]; P = 0.003).Blood pressure-targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest.
Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion.A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition.After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue.The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.
