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Aim: To understand whether the science to date has focused on single or multiple chest compression components and identify the evidence related to chest compression components to determine the need for a full systematic review., Methods: This review was undertaken by members of the International Liaison Committee on Resuscitation and guided by a specific methodological framework and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR). Studies were eligible for inclusion if they were peer-reviewed human studies that examined the effect of different chest compression depths or rates, or chest wall or leaning, on physiological or clinical outcomes. The databases searched were MEDLINE complete, Embase, and Cochrane., Results: Twenty-two clinical studies were included in this review: five observational studies involving 879 patients examined both chest compression rate and depth; eight studies involving 14,285 patients examined chest compression rate only; seven studies involving 12001 patients examined chest compression depth only, and two studies involving 1848 patients examined chest wall recoil. No studies were identified that examined chest wall leaning. Three studies reported an inverse relationship between chest compression rate and depth., Conclusion: This scoping review did not identify sufficient new evidence that would justify conducting new systematic reviews or reconsideration of current resuscitation guidelines. This scoping review does highlight significant gaps in the research evidence related to chest compression components, namely a lack of high-level evidence, paucity of studies of in-hospital cardiac arrest, and failure to account for the possibility of interactions between chest compression components., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Out-of-hospital sudden cardiac arrest is a major public health problem with an overall survival of less than 5%. Upon cardiac arrest, cessation of coronary blood flow rapidly leads to intense myocardial ischemia and activation of the sarcolemmal Na + -H + exchanger isoform-1 (NHE-1). NHE-1 activation drives Na + into cardiomyocytes in exchange for H + with its exchange rate intensified upon reperfusion during the resuscitation effort. Na + accumulates in the cytosol driving Ca 2+ entry through the Na + -Ca 2+ exchanger, eventually causing cytosolic and mitochondrial Ca 2+ overload and worsening myocardial injury by compromising mitochondrial bioenergetic function. We have reported clinically relevant myocardial effects elicited by NHE-1 inhibitors given during resuscitation in animal models of ventricular fibrillation (VF). These effects include: (a) preservation of left ventricular distensibility enabling hemodynamically more effective chest compressions, (b) return of cardiac activity with greater electrical stability reducing post-resuscitation episodes of VF, (c) less post-resuscitation myocardial dysfunction, and (d) attenuation of adverse myocardial effects of epinephrine; all contributing to improved survival in animal models. Mechanistically, NHE-1 inhibition reduces adverse effects stemming from Na + -driven cytosolic and mitochondrial Ca 2+ overload. We believe the preclinical work herein discussed provides a persuasive rationale for examining the potential role of NHE-1 inhibitors for cardiac resuscitation in humans.

Cardiopulmonary resuscitation is a lifesaving technique for victims of sudden cardiac arrest. Despite advances in resuscitation science, basic life support remains a critical factor in determining outcomes. The American Heart Association recommendations for adult basic life support incorporate the most recently published evidence and serve as the basis for education and training for laypeople and healthcare providers who perform cardiopulmonary resuscitation., Competing Interests: The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest., (© 2017 American Heart Association, Inc.)

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 pediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have prioritized and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question., Competing Interests: The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest., (© 2017 American Heart Association, Inc., and European Resuscitation Council.)

Introduction: Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects., Methods: We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls., Results: Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0h cytochrome c levels compared to survivors (3.66ng/mL [1.40, 14.9] vs. 1.27ng/mL [0.16, 2.37], p<0.001). There were significantly higher Ribonuclease P (RNaseP) (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and Beta-2microglobulin (B2M) (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA., Conclusions: Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This review comprises the most extensive literature search and evidence evaluation to date on the most important international BLS interventions, diagnostics, and prognostic factors for cardiac arrest victims. It reemphasizes that the critical lifesaving steps of BLS are (1) prevention, (2) immediate recognition and activation of the emergency response system, (3) early high-quality CPR, and (4) rapid defibrillation for shockable rhythms. Highlights in prevention indicate the rational and judicious deployment of search-and-rescue operations in drowning victims and the importance of education on opioid-associated emergencies. Other 2015 highlights in recognition and activation include the critical role of dispatcher recognition and dispatch-assisted chest compressions, which has been demonstrated in multiple international jurisdictions with consistent improvements in cardiac arrest survival. Similar to the 2010 ILCOR BLS treatment recommendations, the importance of high quality was reemphasized across all measures of CPR quality: rate, depth, recoil, and minimal chest compression pauses, with a universal understanding that we all should be providing chest compressions to all victims of cardiac arrest. This review continued to focus on the interface of BLS sequencing and ensuring high-quality CPR with other important BLS interventions, such as ventilation and defibrillation. In addition, this consensus statement highlights the importance of EMS systems, which employ bundles of care focusing on providing high-quality chest compressions while extricating the patient from the scene to the next level of care. Highlights in defibrillation indicate the global importance of increasing the number of sites with public-access defibrillation programs. Whereas the 2010 ILCOR Consensus on Science provided important direction for the “what” in resuscitation (ie, what to do), the 2015 consensus has begun with the GRADE methodology to provide direction for the quality of resuscitation. We hope that resuscitation councils and other stakeholders will be able to translate this body of knowledge of international consensus statements to build their own effective resuscitation guidelines.

The 2010 guidelines for cardiopulmonary resuscitation recommends that the chest be compressed at least 5 cm, with evidence that depths exceeding 5 cm may further aid resuscitation. The current piston-based mechanical device LUCAS 2™ is programmed to deliver a compression depth of 5 cm. We report 2 cases in which the LUCAS 2™ device failed to generate physiological surrogates of blood flow (ie, end-tidal carbon dioxide tension and aortic diastolic blood pressure) at levels indicative of effective chest compressions. A switch to manual compressions allowing greater compression depth yielded higher end-tidal carbon dioxide tension and arterial blood pressure. These cases depict limitations of the LUCAS 2™ device and the importance of guiding chest compression by physiological parameters. Consideration should be given to modifications to the LUCAS 2™, allowing rescuers to increase depth when required to optimize the hemodynamic efficacy of chest compression.

We compared the efficacy of the novel sodium-hydrogen exchanger (NHE-1) inhibitor AVE4454B with cariporide for resuscitation from ventricular fibrillation (VF) assessing the effects on left ventricular myocardial distensibility during chest compression, myocardial function after the return of spontaneous circulation, and survival. Three groups of 10 rats each were subjected to 10 min of untreated VF and resuscitation attempted by providing chest compression for up to 8 min with the depth of compression adjusted to attain an aortic diastolic pressure between 26 and 28 mmHg (to secure a coronary perfusion pressure above 20 mmHg) followed by electrical shocks. Rats received AVE4454B (1 mg/kg), cariporide (1 mg/kg), or vehicle control immediately before chest compression. We observed that NHE-1 inhibition (NHEI) preserved left ventricular myocardial distensibility during chest compression evidenced by less depth of compression required to attain the target aortic diastolic pressure corresponding to (mean ± standard deviation) 14.1 ± 1.1 mm in the AVE4454B group (P < 0.001 versus control), 15.0 ± 1.4 mm in the cariporide group (P < 0.01 versus control), and 17.0 ± 1.2 mm in controls. When the depth of compression was related to the coronary perfusion pressure generated-an index of left ventricular distensibility-only the cariporide group attained statistical significance. Postresuscitation, both compounds ameliorated myocardial dysfunction evidenced by lesser reductions in mean aortic pressure and the maximal rate of left ventricular pressure increase as well as earlier normalization of left ventricular end-diastolic pressure increases. This effect was associated with improved survival corresponding to 55% in the AVE4454B group (not significant) and 70% in the cariporide group (P < 0.01 versus control by Gehan-Breslow analysis) at 240 min postresuscitation. An inverse correlation was found between plasma cytochrome c and indices of left ventricular function at 240 min postresuscitation suggesting that NHEI exerts beneficial effects in part by attenuating mitochondrial injury. We conclude that cariporide is more effective than AVE4454B for resuscitation from cardiac arrest given its more prominent effect on preserving left ventricular myocardial distensibility and promoting survival., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Erythropoietin activates potent protective mechanisms in non-hematopoietic tissues including the myocardium. In a rat model of ventricular fibrillation, erythropoietin preserved myocardial compliance enabling hemodynamically more effective CPR., Objective: To investigate whether intravenous erythropoietin given within 2 min of physician-led CPR improves outcome from out-of-hospital cardiac arrest., Methods: Erythropoietin (90,000 IU of beta-epoetin, n=24) was compared prospectively with 0.9% NaCl (concurrent controls=30) and retrospectively with a preceding group treated with similar protocol (matched controls=48)., Results: Compared with concurrent controls, the erythropoietin group had higher rates of ICU admission (92% vs 50%, p=0.004), return of spontaneous circulation (ROSC) (92% vs 53%, p=0.006), 24-h survival (83% vs 47%, p=0.008), and hospital survival (54% vs 20%, p=0.011). However, after adjusting for pretreatment covariates only ICU admission and ROSC remained statistically significant. Compared with matched controls, the erythropoietin group had higher rates of ICU admission (92% vs 65%, p=0.024) and 24-h survival (83% vs 52%, p=0.014) with statistically insignificant higher ROSC (92% vs 71%, p=0.060) and hospital survival (54% vs 31%, p=0.063). However, after adjusting for pretreatment covariates all four outcomes were statistically significant. End-tidal PCO(2) (an estimate of blood flow during chest compression) was higher in the erythropoietin group., Conclusions: Erythropoietin given during CPR facilitates ROSC, ICU admission, 24-h survival, and hospital survival. This effect was consistent with myocardial protection leading to hemodynamically more effective CPR (Trial registration: http://isrctn.org. Identifier: ISRCTN67856342).

Reversal of cardiac arrest requires reestablishment of aerobic metabolism by reperfusion with oxygenated blood of tissues that have been ischemic for variable periods of time. However, reperfusion concomitantly activates a myriad of pathogenic mechanisms causing what is known as reperfusion injury. At the center of reperfusion injury are mitochondria, playing a critical role as effectors and targets of injury. Studies in animal models of ventricular fibrillation have shown that limiting myocardial cytosolic Na+ overload attenuates mitochondrial Ca2+ overload and maintains oxidative phosphorylation, which is the main bioenergetic function of mitochondria. This effect is associated with functional myocardial benefits such as preservation of myocardial compliance during chest compression and attenuation of myocardial dysfunction after return of spontaneous circulation. Additional studies in similar animal models of ventricular fibrillation have shown that mitochondrial injury leads to activation of the mitochondrial apoptotic pathway, characterized by the release of cytochrome c to the cytosol, reduction of caspase-9 levels, and activation of caspase-3 coincident with marked reduction in left ventricular function. Cytochrome c also "leaks" into the bloodstream attaining levels that are inversely proportional to survival. These data indicate that mitochondria play a key role during cardiac resuscitation by modulating energy metabolism and signaling apoptotic cascades and that targeting mitochondria could represent a promising strategy for cardiac resuscitation.

More than 50,000 people suffer annually in Spain an episode of out-of-hospital cardiac arrest, but less than 10% of those individuals are successfully resuscitated and return home to live productive lives. The application of the scientific evidence available in resuscitation could substantially improve such dismal outcome. However, most of the procedures that have been able to reduce mortality are not sufficiently being used in Spain. In addition to the development of really intense strategies for early defibrillation, 4 current aspects in resuscitation have the greatest potential for improving outcome: a) prevention of cardiac arrests through recognition of early warning signs and timely intervention; b) flow-based cardiopulmonary resuscitation limiting the role of ventilation; c) use of technology in driving resuscitation interventions, and d) use of hypothermia.

Ca(2+) overload and reactive oxygen species can injure mitochondria during ischemia and reperfusion. We hypothesized that mitochondrial injury occurs during cardiac resuscitation, causing release of cytochrome c to the cytosol and bloodstream while activating apoptotic pathways. Plasma cytochrome c was measured using reverse-phase HPLC and Western immunoblotting in rats subjected to 4 or 8 min of untreated ventricular fibrillation and 8 min of closed-chest resuscitation followed by 240 min of postresuscitation hemodynamic observation. A sham group served as control. Plasma cytochrome c rose progressively to levels 10-fold higher than in sham rats 240 min after resuscitation (P < 0.01), despite reversal of whole body ischemia (decreases in arterial lactate). Cytochrome c levels were inversely correlated with left ventricular stroke work (r = -0.40, P = 0.02). Western immunoblotting of left ventricular tissue demonstrated increased levels of 17-kDa cleaved caspase-3 fragments in the cytosol. Plasma cytochrome c was then serially measured in 12 resuscitated rats until the rat died or cytochrome c returned to baseline. In three survivors, cytochrome c rose slightly to

Purpose of Review: Successful treatment of cardiac arrest requires that an electrically stable and mechanically competent cardiac activity be promptly reestablished. However, many interventions used to attempt to reestablish cardiac activity may also inflict additional myocardial injury and, in turn, compromise resuscitability. In this review, we examine mechanisms of such myocardial injury and discuss potential new strategies for myocardial protection during resuscitation from cardiac arrest., Recent Findings: Efforts are currently directed at understanding underlying mechanisms of myocardial injury associated with current resuscitation methods, with the purpose of developing alternative approaches that are safer and more effective. These new approaches include, among others, the development of alternative low-energy defibrillation waveforms, methods for optimizing the timing for attempting defibrillation, and the use of vasopressor agents devoid of beta-agonist effects. There is also interest in understanding the role that activation of pathways of ischemic and reperfusion injury could play during resuscitation from cardiac arrest. To this end, activation of the sarcolemmal sodium-hydrogen exchanger isoform 1 seems to play an important role. Other potentially important pathways involve adenosine metabolism, activation of potassium ATP channels, and generation of oxygen radical species. These pathways may become novel pharmacologic targets for cardiac resuscitation., Summary: The growing body of research in these areas is bringing hope that in a not so distant future new approaches and interventions for cardiac resuscitation could be available for resuscitation of humans in various clinical settings.

Whereas myocardial cell injury can occur during electrical defibrillation proportional to the energy level of individual shocks, only minimal (or no) injury seems to develop when the energy is limited to the levels typically required to terminate ventricular fibrillation. During cardiac arrest, however, multiple shocks are often required to terminate ventricular fibrillation or to treat episodes that appear subsequently during the resuscitation effort or the postresuscitation interval. Concern exists because an inverse relationship has been reported between the number of electrical shocks delivered during cardiac resuscitation and both resuscitability and survival. Repetitive electrical shocks can alter diastolic function and prompt leftward shifts of the end-diastolic pressure-volume curves. Repetitive shocks may, therefore, contribute to the recently recognized phenomenon of postresuscitation myocardial dysfunction and hamper efforts to reestablish competent myocardial function after resuscitation. Thus, strategies aimed at limiting the number of electrical shocks during cardiopulmonary resuscitation are highly desirable. These may include real-time ventricular fibrillation waveform analysis to improve targeting of individual shocks and efforts (using mechanical and pharmacologic means) to render the myocardium more responsive to individual shocks and to promote greater electrical stability after successful defibrillation.

Objective: To investigate the functional and metabolic changes in the myocardium after successful resuscitation from cardiac arrest., Design: Prospective, randomized, sham-controlled study., Setting: Animal laboratory at a university center., Subjects: Domestic pigs., Interventions: Electric induction of ventricular fibrillation by alternating current delivered to the right ventricular endocardium through a pacing electrode. Electric defibrillation was attempted after an interval of 12 mins of ventricular fibrillation, which included 4 mins of untreated ventricular fibrillation and 8 mins of precordial compression in 13 animals, seven of which were successfully resuscitated. Seven additional animals were randomized to serve as "sham" controls, in which cardiac arrest was not induced., Measurements and Main Results: Left ventricular pressure-volume relationships utilizing the conductance method were obtained in conjunction with conventional hemodynamic and metabolic measurements at baseline and during a 6-hr interval after successful cardiac resuscitation. Progressive and striking increases in left ventricular volumes were observed after successful cardiac resuscitation. The end-diastolic volume increased from a prearrest level of 89 +/- 21 mL to a maximum of 154 +/- 53 mL (p<.05) at 360 mins after successful resuscitation. The time-coincident end-systolic volume increased from 54 +/- 21 to 126 +/- 54 mL (p<.05), such that the ejection fraction was reduced from 0.41 +/- 0.10 to 0.20 +/- 0.07 ( p<.05). Ventricular dilation was associated with marked reductions in stroke volume and ventricular work. However, compensatory increases in heart rate maintained cardiac output at levels that sustained adequate systemic oxygen delivery. The slope of the end-systolic pressure-volume relationships progressively decreased from 5.04 +/- 1.88 to 2.00 +/- 0.57 mm Hg/mL (p<.05) at 360 mins after successful resuscitation. The volume intercept at left ventricular pressure of 100 mm Hg increased from 43 +/- 19 to 94 +/- 51 mL (p=.03). Both the decrease in the slope and the increase in the volume intercept were characteristic of progressive impairment in contractile function. The rate of left ventricular pressure decrease was unchanged. Accordingly, no substantial changes in lusitropic properties were identified. Despite large increases in end-diastolic volume, the end-diastolic pressure remained unchanged., Conclusion: Postresuscitation myocardial dysfunction in this animal model was characterized by impaired contractile function, decreased work capability, and ventricular dilation.

Objectives: To evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO2 as predictors of resuscitability after prolonged cardiac arrest., Design: Prospective, randomized, controlled animal study., Setting: University research laboratory., Subjects: Twenty-one Sprague-Dawley rats, including three groups of seven animals in each group., Interventions: Ventricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted., Measurements and Main Results: All animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO2 produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest., Conclusions: The efficacy of precordial compression--as measured by coronary perfusion pressure and end-tidal CO2 concentration after prolongation of untreated cardiac arrest--was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO2 failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest.

Objective: To evaluate the effect of spontaneous gasping on cardiorespiratory functions and the ability to resuscitate during experimental cardiac arrest., Data Sources: Studies in rat and pig models during cardiac arrest and cardiopulmonary resuscitation (CPR)., Study Selection: We retrospectively examined the role of spontaneous gasping during the course of experimental studies on cardiopulmonary resuscitation., Data Extraction: The data were extracted to illustrate the mechanisms of spontaneous gasping and its effects on pulmonary gas exchange and blood circulation during CPR., Data Synthesis: Spontaneous gasping increased PaO2 and decreased PaCO2 values during precordial compression in the absence of mechanical ventilation. The frequency of gasping during precordial compression was greater in successfully resuscitated animals. A significant linear correlation was established between coronary artery perfusion pressure and both the frequency (r2 = .90, p < .01) and the duration (r2 = 0.69, p < .01) of gasping during untreated ventricular fibrillation and before resuscitation was attempted. Like coronary perfusion pressure, the frequency and duration of gasping predicted the success of cardiac resuscitation attempts., Conclusions: Spontaneous gasping is associated with both pulmonary and hemodynamic effects during cardiac arrest in experimental animals. Spontaneous gasping is biologically useful and is predictive of a more favorable outcome of resuscitative efforts.

Background: After prolonged cardiac arrest, conventional methods of closed-chest cardiac compression are ineffective. This is primarily because of failure to generate minimal threshold levels of coronary perfusion pressure for cardiac resuscitation. This report introduces a new option for cardiac resuscitation by use of a combination of intermittent ascending aortic balloon occlusion, aortic infusion, and precordial compression to increase the pressure gradient for coronary perfusion., Methods and Results: Twenty anesthetized, mechanically ventilated, normovolemic domestic pigs were investigated. A 10F balloon catheter was advanced from the left femoral artery into the ascending aorta. Ventricular fibrillation was induced with an AC current delivered through an electrode catheter advanced into the right ventricle. Precordial compression was initiated after 7 minutes of untreated ventricular fibrillation. The animals were randomized to one of four groups: (1) balloon occlusion with proximal infusion of oxygenated saline, (2) balloon occlusion alone, (3) proximal aortic infusion together with epinephrine without balloon occlusion, and (4) injection of epinephrine without balloon occlusion or proximal infusion. For balloon occlusion, the balloon was inflated for 30 seconds during each minute of cardiopulmonary resuscitation. In the subsets of animals that received infusions, oxygenated saline (30 mL) was injected into the proximal aorta immediately after balloon occlusion. Epinephrine was used in two subsets: It was injected as a bolus in amounts of 30 micrograms/kg into the right atrium at 30 seconds after start of precordial compression and repeated as required to maintain coronary perfusion pressure within the range of 25 to 30 mm Hg. Defibrillation was attempted at 1 minute after start of precordial compression and at 1-minute intervals thereafter. Resuscitation attempts were continued until there was return of spontaneous circulation or for a total of 30 minutes after start of precordial compression. Coronary perfusion pressure generated by precordial compression was significantly increased after balloon occlusion. Each of 10 animals was successfully resuscitated and survived for 48 hours after balloon occlusion whether or not it was combined with infusion. Three of five animals were resuscitated by a combination of infusion and epinephrine in the absence of aortic occlusion, but none survived for 48 hours (P = .02). Only one epinephrine-treated animal was successfully resuscitated and survived for 48 hours in the absence of balloon occlusion or infusion (P < .05)., Conclusions: Ascending aortic balloon occlusion with or without proximal aortic infusion strikingly increased resuscitability and 48-hour survival after cardiac arrest under conditions when conventional methods failed.

Objective: To define changes in intramyocardial pH and PCO2 during cardiac arrest and resuscitation., Design: Prospective and observational trial., Setting: Mammalian research laboratory utilizing a porcine model of cardiac arrest., Subjects: Sixteen domestic pigs., Interventions: Ventricular fibrillation was induced by an alternating current delivered to the epicardium. Precordial compression was begun after 3 mins of untreated cardiac arrest and was initially adjusted to produce a coronary perfusion pressure of 10 mm Hg. Electrical defibrillation was attempted after an additional 8 mins of precordial compression., Measurements and Main Results: A rapid-response, ion-selective field effect transistor sensor was adapted for measurement of intramyocardial PCO2. Intramyocardial PCO2 progressively increased from 54 to 346 torr (7.2 to 46.1 kPa) during the 11-min interval of cardiac arrest. Intramyocardial hydrogen ion concentrations were simultaneously measured with a glass electrode. The intramyocardial hydrogen ion value increased from 65 nmol/L (pH 7.20) to 441 nmol/L (pH 6.38) over the same interval. The increases in myocardial PCO2 were inversely correlated with coronary perfusion pressure and with the likelihood of successful resuscitation. Within 30 mins after successful cardiac resuscitation, myocardial PCO2 had almost completely returned to prearrest levels., Conclusions: Striking increases in myocardial PCO2 and hydrogen ion values accompany the global myocardial ischemia of cardiac arrest. The increases in myocardial PCO2, rather than decreases in pH, reflected more precisely the hemodynamic efficacy of the resuscitation effort, correlated inversely with coronary perfusion pressure, and predicted the likelihood of successful resuscitation.

Background: The severity of spontaneous myocardial hypercarbic acidosis during cardiac arrest previously has been predictive of the likelihood of restoring spontaneous circulation. The present study investigated whether hypercarbia itself impairs cardiac resuscitation. Since coronary perfusion pressure is the overriding determinant of cardiac resuscitability, we used a porcine model of cardiac arrest in which coronary perfusion pressure was controlled., Methods: In 31 domestic pigs anesthetized with pentobarbital, the lungs were mechanically ventilate. Myocardial carbon dioxide tension and hydrogen ion concentration were measured by sensors advanced into the myocardium. After 15 min of untreated ventricular fibrillation, venoarterial extracorporeal circulation was initiated. Animals were randomized to receive a carbon dioxide gas fraction in the extracorporeal perfusate of 0.00, 0.10, 0.30, or 0.50 with oxygen concentration maintained constant at 0.50. Extracorporeal flow was adjusted to maintain a coronary perfusion pressure in the range of 60-80 mmHg, a level of predictive resuscitability., Results: The proportion of animals successfully resuscitated and the proportion of animals maintaining spontaneous circulation for 60 min or longer decreased with increasing perfusate PCO2 and concurrent increases in myocardial CO2 tension in the absence of altered oxygen utilization (P < .01)., Conclusions: Hypercarbia, in this experimental setting, was therefore a quantitative determinant of both myocardial resuscitability and the restoration of spontaneous circulation.

Open-chest direct cardiac compression represents a more potent but highly invasive option for cardiac resuscitation when conventional techniques of closed-chest cardiac resuscitation fail after prolonged cardiac arrest. We postulated that venoarterial extracorporeal circulation might be a more effective intervention with less trauma. In the setting of human cardiac resuscitation, however, controlled studies would be limited by strategic constraints. Accordingly, the effectiveness of open-chest cardiac compression was compared with that of extracorporeal circulation after a 15-min interval of untreated ventricular fibrillation in a porcine model of cardiac arrest. Sixteen domestic pigs were randomized to resuscitation by either peripheral venoarterial extracorporeal circulation or open-chest direct cardiac compression. During resuscitation, epinephrine was continuously infused into the right atrium, and defibrillation was attempted by transthoracic countershock at 2-min intervals. Systemic blood flows averaged 198 ml.kg-1.min-1 with extracorporeal circulation. This contrasted with direct cardiac compression, in which flows averaged only 40 ml.kg-1.min-1. Coronary perfusion pressure, the major determinant of resuscitability on the basis of earlier studies, was correspondingly lower (94 vs 29 mm Hg). Extracorporeal circulation, in conjunction with transthoracic DC countershock and epinephrine, successfully reestablished spontaneous circulation in each of eight animals after 15 min of untreated ventricular fibrillation. This contrasted with the outcome after open-chest cardiac compression, in which spontaneous circulation was reestablished in only four of eight animals (p = .038). We conclude that extracorporeal circulation is a more effective alternative to direct cardiac compression for cardiac resuscitation after protracted cardiac arrest.

When immediate defibrillation fails, successful cardiac resuscitation is contingent on prompt reestablishment of myocardial blood flow. Conventional methods of closed-chest resuscitation generates only critical levels of myocardial blood flow and therefore are of limited value for successful resuscitation. Methods that optimize the site, depth, rate and duration of precordial compression may increase myocardial blood flow, however, the lack of objective measurements of their hemodynamic effects limits the optimal performance of this resuscitation method. With the recognition that elimination of CO2 is flow limited, measurement of end-expired PCO2 has emerged as a practical option for continuous assessment of systemic blood flow and coronary perfusion pressure. With measurement of the end-expired PCO2, operator fatigue may be recognized, the technique of precordial compression may be optimized, and the likelihood of restoring spontaneous circulation may be estimated. When conventional cardiac resuscitation fails or is predicted to fail by measurements of end-tidal PCO2, more effective interventions such as open-chest direct cardiac massage may be instituted. Regarding the vast resuscitation polypharmacy, only agents that act by selectively augmenting coronary perfusion pressure and myocardial blood flow are of proven benefit for successful resuscitation.

Objective: --To investigate the effects of hypertonic buffer solutions on coronary perfusion pressure (CPP) and resuscitability during experimental closed-chest cardiac resuscitation., Design: --Randomized, placebo-controlled trial., Setting: --Mammalian research laboratory., Participants: --Forty-four domestic pigs., Interventions: --Cardiac arrest was induced by ventricular fibrillation in mechanically ventilated pigs anesthetized with pentobarbital sodium. Precordial compression was started at the third minute of untreated ventricular fibrillation and maintained for an interval of 8 minutes. A hypertonic solution of sodium bicarbonate, Carbicarb (an equimolar mixture of sodium bicarbonate and sodium carbonate [International Medication Systems, Ltd]), or sodium chloride or an isotonic solution of sodium chloride was infused into the right atrium over a 1-minute interval starting at the sixth minute of ventricular fibrillation. Restoration of spontaneous circulation was attempted by DC transthoracic countershock after 11 minutes of ventricular fibrillation., Main Outcome Measures: --Plasma osmolality, CPP, and cardiac resuscitability., Results: --Infusion of hypertonic buffer and sodium chloride solutions increased plasma osmolality from an average of 280 to 330 mOsm/kg. This was accompanied by a significant decrease in the aortic pressures and CPPs generated during precordial compression. No such changes occurred after infusion of isotonic sodium chloride. Restoration of spontaneous circulation, as in earlier studies, was contingent on the levels of CPP prior to attempted defibrillation. Accordingly, none of 13 animals in which the CPP declined to less than 10 mm Hg after infusion of the hypertonic solutions were successfully resuscitated. This contrasted with nine animals that received isotonic sodium chloride and served as controls. Coronary perfusion pressure consistently exceeded 10 mm Hg in these control animals, and spontaneous circulation was restored in each instance., Conclusions: --Hypertonic solutions and specifically buffer solutions administered in the absence of vasopressor agents may adversely affect cardiac resuscitation efforts by reducing CPP below critical thresholds.

After cardiac arrest, return of cardiac function and effective circulation are contingent on prompt restoration of myocardial blood flow. Because conventional closed-chest CPR has limited hemodynamic efficiency, we investigated venoarterial ECC utilizing peripheral vascular access as an alternative for cardiac resuscitation. Ventricular fibrillation was induced in domestic pigs by alternating current delivered to the endocardium of the right ventricle. Conventional closed-chest CPR was begun after 10 minutes. In each instance, precordial compression and external defibrillation failed to restore a viable rhythm. ECC was begun at 15 minutes at an average flow rate of 183 ml/kg/min. In each of eight animals, sinus rhythm was restored. In six of these eight animals, spontaneous circulation was reestablished after an average interval of 152 minutes. When epinephrine was administered concomitantly with ECC in an additional eight animals so as to maintain mean aortic pressure between 60 and 100 mm Hg, sinus rhythm and spontaneous circulation were reestablished in each pig after an average of only 23 minutes. The effects of ECC in conjunction with epinephrine were then compared with those of conventional precordial compression in conjunction with epinephrine (sham ECC). In contrast to ECC, which successfully resuscitated each of five animals, none of five sham ECC-treated animals was resuscitated by continued precordial compression and maximal doses of epinephrine (p less than 0.01). We conclude that ECC in conjunction with epinephrine emerges as a highly effective experimental intervention for resuscitation when conventional techniques of precordial compression and external defibrillation fail to reverse cardiac arrest.

After failure of external defibrillation, return of cardiac activity with spontaneous circulation is contingent on rapid and effective reversal of myocardial ischemia. Closed-chest cardiopulmonary resuscitation (CPR) evolved about 30 years ago and was almost universally implemented by both professional providers and lay bystanders because of its technical simplicity and noninvasiveness. However, there is growing concern since the limited hemodynamic efficacy of precordial compression accounts for a disappointingly low success rate; especially so if there is a delay of more than 3 minutes before resuscitation is started. There is also increasing concern with the lack of objective hemodynamic measurements currently available for the assessment and quantitation of the effectiveness of resuscitation efforts. Accordingly, the resuscitation procedure proceeds without confirmation that it increases systemic and myocardial blood flows to levels that would be likely to restore spontaneous circulation. Continuous monitoring of end-tidal carbon dioxide (PETCO2) now appears to be a practical measurement which provides a noninvasive quantitative indication of both systemic blood flow and coronary perfusion pressure. Consequently, PETCO2 predicts the likelihood of successful resuscitation and guides the operator who may modify the technique of precordial compression to improve systemic and myocardial perfusion. Among the large polypharmacy for cardiac resuscitation, only alpha-adrenergic agents (which increase coronary perfusion pressure) and especially epinephrine are of proven benefit. Neither buffer agents nor calcium salts appear to improve outcome except under unique conditions. To the contrary, there is increasing awareness of adverse effects of pharmacologic interventions such that they may hinder the return of viable myocardial and cerebral function. This has constrained the routine use of all drugs except for the use of alpha-adrenergic agonists. More invasive interventions by which blood flow is restored such as open-chest cardiac massage or extra-corporeal pump oxygenation (ECPO) are consistently more effective than conventional CPR. Experimentally, both methods promptly restore systemic and myocardial perfusion to viable levels and thereby increase the likelihood that spontaneous circulation is restored even after prolonged cardiac arrest or failure of conventional CPR.

We investigated the effects of carbon dioxide-producing and carbon dioxide-consuming buffers on intramyocardial pH and on cardiac resuscitability. In 29 pigs, intramyocardial pH was continuously measured with a glass electrode advanced into the midmyocardium of the posterior left ventricle through a diaphragmatic window. Ventricular fibrillation (VF) was electrically induced by alternating current applied to the epicardium of the left ventricle. After 3 minutes of VF, precordial compression was begun and continued for an interval of 8 minutes. Sodium bicarbonate (a carbon dioxide-generating buffer), Carbicarb (a carbon dioxide-consuming buffer), and hypertonic sodium chloride (control solution) were infused into the right atrium during cardiac resuscitation. Defibrillation was attempted by transthoracic direct-current shock after 11 minutes of VF. Intramyocardial pH progressively decreased from an average value of 7.26 before VF to 6.87 before infusion of buffers. Systemic circulation and great cardiac vein pH significantly increased after administration of the two buffer agents. However, intramyocardial pH continued to decline to an average of 6.62 after 11 minutes of VF, and this decline was not altered by either buffer solution or by the saline control. As in previous studies, resuscitability was closely related to coronary perfusion pressure at the time of direct-current countershock but not to pH. Accordingly, the rationale of reversing acidosis by the administration of these buffer agents is not supported. Even more important, neither carbon dioxide-consuming nor carbon dioxide-producing buffers altered myocardial acidosis or improved myocardial resuscitability under controlled experimental conditions of cardiac arrest.

We investigated the aortic, mixed venous, and great cardiac vein acid-base changes in eight domestic pigs during cardiac arrest produced by ventricular fibrillation and during cardiopulmonary resuscitation (CPR). The great cardiac vein PCO2 increased from a control value of 52 +/- 2 to 132 +/- 28 (SD) Torr during CPR, whereas the arterial PCO2 was unchanged (39 +/- 4 vs. 38 +/- 4). The coronary venoarterial PCO2 gradient, therefore, increased remarkably from 13 +/- 2 to 94 +/- 29 Torr. The simultaneously measured great cardiac vein lactate concentrations increased from 0.24 +/- 0.06 to 7.3 +/- 2.34 mmol/l. Much more moderate increases in the lactate content of aortic blood from 0.64 +/- 0.25 to 2.56 +/- 0.27 mmol/l were observed. Increases in great cardiac vein PCO2 and lactate were highly correlated during CPR (r = 0.91). After successful CPR, the coronary venoarterial PCO2 gradient returned to normal levels within 2 min after restoration of spontaneous circulation. Lactate content was rapidly reduced and lactate extraction was reestablished within 30 min after CPR. These studies demonstrate marked but reversible acidosis predominantly as the result of myocardial CO2 production during CPR.

1. Calcium-entry blockers increase the intramyocardial pH and decrease the intramyocardial Pco2 of ischaemic canine myocardium. However, the evidence documenting improvements in myocardial acidosis and in myocardial resuscitability after administration of calcium-entry blockers during cardiac arrest is incomplete. We therefore compared the effects of verapamil (0.05 mg/kg) and diltiazem (0.075 mg/kg) with those of saline placebo in an established porcine model of cardiac arrest and cardiopulmonary resuscitation. 2. After verapamil, six of 11 animals were successfully resuscitated; after diltiazem, five of 10; and after saline placebo, six of 10. Coronary perfusion and mean aortic pressures together with end-tidal CO2 concentration during precordial compression were predictive of resuscitation, independently of the drug or placebo. 3. Coronary vein pH decreased to 6.91 +/- 0.06 units (mean +/- SEM) with concurrent increases in PCO2 to levels exceeding 100 mmHg. Coronary vein lactate increased to a maximum of 7.5 +/- 0.6 mmol/l. Coronary vein acidaemia was accompanied by decreases in intramyocardial pH to 6.64 +/- 0.06 units. However, each of these differences between success and failure of resuscitation was unrelated to treatment with calcium-entry blockers. 4. Accordingly, neither verapamil nor diltiazem selectively altered coronary perfusion pressure, attenuated intramyocardial acidosis or improved resuscitability after porcine cardiac arrest and cardiopulmonary resuscitation.

A standardized method of cardiopulmonary resuscitation in rodents has been developed for anesthetized, mechanically ventilated rats. Ventricular fibrillation was induced and maintained by an alternating current delivered to the right ventricular endocardium. After 4 min of ventricular fibrillation, the chest was compressed with a pneumatic piston device. Eight of 14 animals were successfully resuscitated with DC countershock after 6 min of cardiac arrest. In confirmation of earlier studies from our laboratories in dogs, pigs, and human patients, this rodent model of cardiopulmonary resuscitation demonstrated large venoarterial [H+] and PCO2 gradients associated with reduced pulmonary excretion of CO2 during the low-flow state. Mean aortic pressure, coronary perfusion pressure, and end-tidal CO2 during chest compression were predictive of successful resuscitation.

End-tidal PCO2 (PetCO2) is a quantitative indicator of pulmonary blood flow generated by precordial compression and therefore predicts resuscitability during CPR. A striking increase in PetCO2 follows return of spontaneous circulation. Since PaCO2 is closely related to alveolar PCO2 (PACO2) and therefore PetCO2, we hypothesized that PaCO2 may itself serve as an indicator of the blood flow generated during CPR. In a porcine model of cardiac arrest, PaCO2 during precordial compression was highly correlated with PetCO2 (r = .89), cardiac output (r = .72), and coronary perfusion pressure (CPP) (r = .74). In 14 successfully resuscitated animals, PaCO2, PetCO2, and CPP during precordial compression were significantly higher than in nine nonresuscitated animals. After restoration of spontaneous circulation, there was a marked increase in PaCO2 to levels exceeding control values, which corresponded to the sharp increase in PetCO2 that is characteristic of successful resuscitation. We therefore confirm that both PetCO2 and PaCO2 correspond to the pulmonary blood flow and therefore cardiac output which is generated by precordial compression during CPR. Moreover, both serve as prognosticators of cardiac resuscitability and early indicators that spontaneous circulation has been restored.

During cardiac arrest (no flow) and CPR (low flow), the onset of myocardial ischemia is followed by myocardial respiratory acidosis. Myocardial contractility is more decreased by respiratory than by metabolic acidosis. We demonstrated in a porcine model of cardiac arrest and in human patients increases in mixed venous PCO2 during CPR, whereas PaCO2 was decreased. Consequently, there was a striking increase in the venoarterial gradients for both [H+] and CO2. Both cardiac output (pulmonary blood flow) and the concentration of expired CO2 were simultaneously decreased. In great cardiac vein blood, even more profound respiratory acidosis with only minor decreases in bicarbonate and only moderate increases in lactate were observed. Intramyocardial pH was profoundly decreased. The severity of respiratory acidosis as a determinant of resuscitability and survival should be further investigated.

It is generally believed that metabolic acidosis prevails during cardiac arrest. However, recent experimental and clinical studies have demonstrated that respiratory acidosis in mixed venous blood and respiratory alkalosis in arterial blood with only minor increases in lactic acid characterize the early acid-base changes that follow cardiac arrest and cardiopulmonary resuscitation (CPR). While continued CO2 production with critical reduction in systemic perfusion explains the accumulation of CO2 in the venous side, the reduction of pulmonary blood flow with maintenance of constant minute ventilation explains the decreases in expired CO2 and therefore arterial PCO2. In the heart, marked increases in CO2 tension and lactic acid are associated with dramatic decreases in myocardial pH with consequent depression of contractile function. Administration of sodium bicarbonate, however, neither increases resuscitability nor improves long term outcome. Moreover, adverse effects stemming from increases in plasma osmolality, increases in hemoglobin-O2 affinity, induction of alkalemia and generation of CO2 are potentially deleterious for myocardial and cerebral function. Consequently, the American Heart Association has recently discouraged the routine administration of bicarbonate during the initial 10 minutes of CPR in which interventions with proven efficacy such as artificial ventilation, precordial compression, electric defibrillation and epinephrine administration take place. Alternative experimental buffer therapy with agents that consume CO2 have also failed to alter the outcome of cardiac arrest.

Previous studies from our institution demonstrated significant hypercarbic acidosis in the mixed venous (pulmonary artery) blood in animals and human patients during cardiac arrest and cardiopulmonary resuscitation (CPR). In the present study, the acid-base state of the myocardium during cardiac arrest was investigated. Cardiac arrest was electrically induced in 11 pentobarbital-anesthetized and mechanically ventilated domestic pigs. Precordial compression was begun 3 minutes after onset of ventricular fibrillation and continued for 8 minutes. During CPR, there was rapid onset of profound myocardial acidosis with an increase in intramyocardial [H+] from 54 +/- 5 to 146 +/- 20 nmol/l (7.27 +/- 0.04 to 6.88 +/- 0.20 pH units). Great cardiac vein PCO2 increased from 57 +/- 2 to 158 +/- 12 mm Hg. Profound hypercarbic acidosis in great cardiac vein blood was associated with myocardial lactate production to levels of 8.1 +/- 0.7 mmol/l. Only moderate decreases in cardiac vein bicarbonate concentrations from 31 +/- 1 to 23 +/- 1 mmol/l were observed. These acid-base changes were almost completely reversed over an interval of 60 minutes after the animals were successfully resuscitated by DC countershock. The PCO2 in cardiac vein blood was significantly greater than that of mixed venous blood, demonstrating disproportionate myocardial production of CO2 during CPR. Accordingly, it is CO2 production during ischemia that is implicated as the predominant mechanism accounting for myocardial [H+] increases during cardiac arrest. Important clinical implications for buffer therapy during CPR and, in particular, treatment with bicarbonate emerge from these observations.