Giuseppe Ristagno

Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation.

Objective: Epinephrine has been the primary drug for cardiopulmonary resuscitation (CPR) for more than a century. The therapeutic rationale was to restore threshold levels of myocardial and cerebral blood flows by its alpha1 (&agr;1) and alpha2 (&agr;2)-adrenergic agonist vasopressor actions. On the basis of coincidental observations on changes in microvascular flow in the cerebral cortex, we hypothesized that epinephrine selectively decreases microvascular flow. Design: Randomized prospective animal study. Setting: University-affiliated research laboratory. Subjects: Domestic pigs. Interventions: Four groups of five male domestic pigs weighing 40 ± 3 kg were investigated. After induction of anesthesia, endotracheal intubation was followed by mechanical ventilation. A frontoparietal bilateral craniotomy was created. Ventricular fibrillation was induced and untreated for 3 minutes before the start of precordial compression, mechanical ventilation, and attempted defibrillation. Animals were randomized to receive central venous injections during CPR of 1) placebo, 2) epinephrine, 3) epinephrine in which both &agr;1- and beta (&bgr;)-adrenergic effects were blocked by previous administration of prazosin and propranolol, and 4) epinephrine in which both &agr;2- and &bgr;-adrenergic effects were blocked by previous administration of yohimbine and propranolol. Measurements and Main Results: Cerebral cortical microcirculatory blood flow (MBF) was measured with orthogonal polarization spectral imaging. Cerebral cortical carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were concurrently measured using miniature tissue optical sensors. Each animal was resuscitated. No differences in the number of electrical shocks for defibrillation or in the duration of CPR preceding return of spontaneous circulation were observed. Yet when epinephrine induced increases in arterial pressure, it significantly decreased Pbo2 tension and increased Pbco2 tension. Epinephrine therefore significantly decreased MBF and increased indicators of cerebral ischemia. Reduced MBF and magnified brain tissue ischemia during and after cardiopulmonary resuscitation were traced to the &agr;1-adrenergic agonist action of epinephrine. When the &agr;2 effects of epinephrine were blocked, reduced MBF and tissue ischemia persisted. No differences in cardiac output, end tidal Pco2, arterial Po2 and Pco2, and brain temperature were observed before inducing cardiac arrest and following return of spontaneous circulation. Conclusions: In this model, epinephrine through its &agr;1-agonist action had adverse effects on cerebral microvascular blood flow such as to increase the severity of cerebral ischemia during CPR.

Part 3: Adult Basic Life Support and Automated External Defibrillation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

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.

Favourable survival of in-hospital compared to out-of-hospital refractory cardiac arrest patients treated with extracorporeal membrane oxygenation: An Italian tertiary care centre experience

OBJECTIVE Extracorporeal membrane oxygenation (ECMO) support has been suggested to improve the survival rate in patients with refractory in- and out-of-hospital cardiac arrest (IHCA and OHCA). The aim of our study is to report our experience with ECMO in these patients. DESIGN Retrospective, single-centre, observational study. PATIENTS From January 2006 to February 2011 we studied 42 patients (31 males) with refractory cardiac arrest. MEASUREMENT AND MAIN RESULTS ECMO implantation was successful in 38 (90%) of the 42 patients. ECMO support was positioned: three times (8%) in the operating room, six (16%) in the cardiac surgery intensive care unit, 21 (55%) in the emergency room, five (13%) in the catheterisation laboratory and three (8%) in the general ward. A total of 14 IHCA (58%) and three OHCA (16%) patients were weaned from ECMO (p<0.05). Eleven IHCA (46%) and one OHCA (5%, p<0.05) patients were discharged from intensive care unit (ICU). Among IHCA patients, 10 were alive at 6 months, nine of whom (38%) with good neurological outcome. Among OHCA patients weaned from ECMO, one was alive at 6 months with good neurological outcome (5%, p<0.05 vs. IHCA). CONCLUSIONS ECMO support should be considered as a resuscitation alternative in selected patients. More specifically, patients with witnessed IHCA benefit more from ECMO treatment compared to those who experience an out-of-hospital cardiac arrest.

Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation.

Objectives:Both epinephrine and vasopressin increase aortic and carotid arterial pressure when administered during cardiopulmonary resuscitation. However, we recently demonstrated that epinephrine reduces cerebral cortical microcirculatory blood flow. Accordingly, we compared the effects of nonadrenergic vasopressin with those of epinephrine on cerebral cortical microvascular flow together with cortical tissue Po2 and Pco2 as indicators of cortical tissue ischemia. Design:Randomized, prospective animal study. Setting:University-affiliated research laboratory. Subjects:Domestic pigs. Measurements and Main Results:The tracheae of ten domestic male pigs, weighing 40 ± 2 kg, were noninvasively intubated, and the animals were mechanically ventilated. A frontoparietal bilateral craniotomy was created. Microcirculatory blood flow was quantitated with orthogonal polarization spectral imaging. Blood flow velocity in pial and cortical penetrating vessels measuring <20 μm was graded from 0 (no flow) to 3 (normal). Cerebral cortical tissue carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were measured concurrently using miniature optical sensors. Ventricular fibrillation, induced with an alternating current delivered to the right ventricular endocardium, was untreated for 3 mins. Animals were then randomized to receive central venous injections of equipressor doses of epinephrine (30 μg/kg) or vasopressin (0.4 units/kg) at 1 min after the start of cardiopulmonary resuscitation. After 4 mins of cardiopulmonary resuscitation, defibrillation was attempted. Spontaneous circulation was restored in each animal. However, postresuscitation microvascular flows and Pbo2 were greater and Pbco2 less after vasopressin when compared with epinephrine. We observed that a significantly greater number of cortical microvessels were perfused after vasopressin. Conclusions:Cortical microcirculatory blood flow was markedly reduced after epinephrine, resulting in a greater severity of brain ischemia after the restoration of spontaneous circulation in contrast to the more benign effects of vasopressin.

Part 4: Advanced life support

The International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support (ALS) Task Force performed detailed systematic reviews based on the recommendations of the Institute of Medicine of the National Academies1 and using the methodological approach proposed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group.2 Questions to be addressed (using the PICO [population, intervention, comparator, outcome] format)3 were prioritized by ALS Task Force members (by voting). Prioritization criteria included awareness of significant new data and new controversies or questions about practice. Questions about topics no longer relevant to contemporary practice or where little new research has occurred were given lower priority. The ALS Task Force prioritized 42 PICO questions for review. With the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library). By using detailed inclusion and exclusion criteria, articles were screened for further evaluation. The reviewers for each question created a reconciled risk of bias assessment for each of the included studies, using state-of-the-art tools: Cochrane for randomized controlled trials (RCTs),4 Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 for studies of diagnostic accuracy,5 and GRADE for observational studies that inform both therapy and prognosis questions.6 GRADE evidence profile tables7 were then created to facilitate an evaluation of the evidence in support of each of the critical and important outcomes. The quality of the evidence (or confidence in the estimate of the effect) was categorized as high, moderate, low, or very low,8 based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias).9 These evidence profile tables were then used to create a …

Part 3: Adult Basic Life Support and Automated External Defibrillation

This Part of the 2015 International Consensus on Cardiopul monary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) Science With Treatment Recommendations (CoSTR) presents the consensus on science and treatment recommendations for adult basic life support (BLS) and automated external defibrillation (AED). After the publication of the 2010 CoSTR, the Adult BLS Task Force developed review questions in PICO (population, intervention, comparator, outcome) format.1 This resulted in the generation of 36 PICO questions for systematic reviews. The task force discussed the topics and then voted to prioritize the most important questions to be tackled in 2015. From the pool of 36 questions, 14 were rated low priority and were deferred from this round of evidence evaluation. Two new questions were submitted by task force members, and 1 was submitted via the public portal. Two of these (BLS 856 and BLS 891) were taken forward for evidence review. The third question (368: Foreign-Body Airway Obstruction) was deferred after a preliminary review of the evidence failed to identify compelling evidence that would alter the treatment recommendations made when the topic was last reviewed in 2005.2 Each task force performed a systematic review using detailed inclusion and exclusion criteria, based on the recommendations of the Institute of Medicine of the National Academies.3 With the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library). Reviewers were unable to identify any relevant evidence for 3 questions (BLS 811, BLS 373, and BLS 348), and the evidence review was not completed in time for a further question (BLS 370). A revised PICO question was developed for the opioid question (BLS 891). The task force reviewed 23 PICO questions for the …

Electrocardiogram waveforms for monitoring effectiveness of chest compression during cardiopulmonary resuscitation.

Background:Newer guidelines address the importance of effective chest compressions, citing evidence that this primary intervention is usually suboptimally performed during cardiopulmonary resuscitation. We therefore sought a readily available option for monitoring the effectiveness of chest compressions, specifically using the electrocardiogram. Methods and Results:Ventricular fibrillation was induced by coronary artery occlusion and untreated for 5 mins. Male domestic pigs weighing 40 ± 2 kg were randomized to optimal or suboptimal chest compressions after onset of ventricular fibrillation. Optimal depth of mechanical compression in six animals was defined as a decrease of 25% in anterior posterior diameter of the chest during compression. Suboptimal compression, also in six animals, was defined as a decrease of 17.5% in anterior posterior diameter. For each group, the chest compressions were maintained at a rate of 100 per min. After 3 mins of chest compression, defibrillation was attempted with a 150-J biphasic shock. All animals had return of spontaneous circulation after optimal compressions. This contrasted with suboptimal compressions, after which none of the animals had return of spontaneous circulation. Amplitude spectrum area values, representing the electrocardiographic amplitude frequency spectral area computed from conventional precordial leads, like coronary perfusion pressure and end tidal Pco2, were predictive of outcomes. Conclusion:The effectiveness of chest compressions was reflected in the amplitude spectrum area values. Accordingly, the amplitude spectrum area predictor may be incorporated in current automated external defibrillators to monitor and prompt the effectiveness of chest compression during cardiopulmonary resuscitation.

The effects of epinephrine on outcomes of normothermic and therapeutic hypothermic cardiopulmonary resuscitation

Objective:To investigate the effects of epinephrine when administered during either normothermic or therapeutic hypothermic cardiopulmonary resuscitation on postresuscitation myocardial and cerebral function and survival. Design:Prospective, randomized, placebo-controlled experimental study. Setting:University-affiliated animal research laboratory. Subjects:Thirty-two healthy male Sprague-Dawley rats. Interventions:Ventricular fibrillation was induced and untreated for 8 mins. The animals were then randomly assigned to one of four groups: normothermic placebo control; normothermic epinephrine; hypothermic placebo control; and hypothermic epinephrine. Hypothermia was initiated coincident with the start of cardiopulmonary resuscitation. The blood temperature was reduced and maintained at 32 ± 0.2°C and continued for 4 hrs after resuscitation. Normothermic animals were maintained at 37 ± 0.2°C. Either placebo or epinephrine (20 &mgr;g/kg) was administered 5 mins after the start of cardiopulmonary resuscitation and 3 mins before defibrillation. Measurements and Main Results:Postresuscitation cardiac output, ejection fraction, and myocardial performance index were measured hourly for 4 hrs after resuscitation; neurologic deficit scores were measured daily for 7 days, and durations of survival were observed for up to 3 mos. Except for three normothermic control animals, all animals were resuscitated. When epinephrine was administered during normothermic cardiopulmonary resuscitation, postresuscitation myocardial function was severely impaired when compared with the normothermic control group. However, postresuscitation myocardial function was significantly better in animals treated with epinephrine during hypothermic cardiopulmonary resuscitation when compared with hypothermic controls. This was associated with significantly fewer postresuscitation ventricular arrhythmias, less ST-segment elevation, better postresuscitation neurologic deficit scores, and longer duration of survival. Conclusions:Epinephrine, when administered during normothermic cardiopulmonary resuscitation, significantly increases the severity of postresuscitation myocardial dysfunction and decreases the duration of survival. These detrimental effects of epinephrine, however, no longer exist when it is administered during therapeutic hypothermic cardiopulmonary resuscitation.

Cerebral cortical microvascular flow during and following cardiopulmonary resuscitation after short duration of cardiac arrest

AIM To examine changes in cerebral cortical macro- and microcirculation and their relationship to the severity of brain ischaemia during and following resuscitation from a short duration of cardiac arrest. METHODS Bilateral cranial windows were created in eight domestic pigs weighing 41+/-1 kg, exposing the frontoparietal cortex for orthogonal polarization spectral imaging together with estimation of cortical-tissue partial pressure of carbon dioxide, a quantitator of the severity of cerebral ischaemia. After 3 min of untreated ventricular fibrillation, cardiopulmonary resuscitation was begun and continued for 4 min before defibrillation. Aortic pressure, end-tidal and cortical-tissue partial pressure of carbon dioxide, and cortical microcirculatory blood flow in vessels of less and more than 20 microm in diameter were continuously measured. RESULTS Cerebral microcirculatory blood flow progressively decreased over the 3-min interval that followed onset of ventricular fibrillation. Chest compression restored cortical microvascular flow to approximately 40% of the pre-arrest value. Following return of spontaneous circulation, microvascular flow velocity was restored to baseline values over 3 min. Reversal of cerebral ischaemia with normalisation of cerebral cortical-tissue partial pressure of carbon dioxide occurred over 7 min after resuscitation. Cortical microcirculatory blood flow in microvessels less than 20 microm was highly correlated with flow in vessels more than 20 microm together with mean aortic pressure and end-tidal partial pressure of carbon dioxide. CONCLUSION Cerebral cortical microcirculatory flow ceased only 3 min after onset of cardiac arrest. Flow was promptly restored to 40% of its pre-arrest value after start of chest compression. After resuscitation, both macro- and microcirculatory flows were fully restored over 3 min, but cerebral ischaemia reversed more slowly.

Survival and neurological outcomes after nasopharyngeal cooling or peripheral vein cold saline infusion initiated during cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest.

Objective:We have previously demonstrated that nasopharyngeal cooling initiated during cardiopulmonary resuscitation improves the success of resuscitation. In this study, we compared the effects of nasopharyngeal cooling with cold saline infusion initiated during cardiopulmonary resuscitation on resuscitation outcome in a porcine model of prolonged cardiac arrest. We hypothesized that nasopharyngeal cooling initiated during cardiopulmonary resuscitation would yield better resuscitation outcome when compared with cold saline infusion. Design:Randomized, prospective animal study. Setting:University-affiliated research laboratory. Subjects:Yorkshire-X domestic pigs (Sus scrofa). Interventions:Ventricular fibrillation was induced in 14 pigs weighing 38 ± 2 kg. After 15 mins of untreated ventricular fibrillation, cardiopulmonary resuscitation was performed for 5 mins before defibrillation. Coincident with the start of cardiopulmonary resuscitation, animals were randomly assigned to receive nasopharyngeal cooling with the aid of the RhinoChill Device (BeneChill, San Diego, CA) or cold saline infusion with 30 mL/kg 4°C saline. One hour after restoration of spontaneous circulation, surface cooling was begun with the aid of a water blanket in both groups and maintained for 4 hrs. Measurements and Main Results:Jugular vein temperature significantly decreased in animals subjected to nasopharyngeal cooling in comparison with those receiving cold saline infusion (p < .01). Core temperature, however, decreased only in animals receiving cold saline infusion (p < .01). Coronary perfusion pressure was significantly higher in the animals treated with nasopharyngeal cooling (p = .02). All seven animals treated with nasopharyngeal cooling were successfully resuscitated in contrast to only two animals resuscitated in the cold saline infusion group (p = .02). Conclusion:In this model, nasopharyngeal cooling initiated during cardiopulmonary resuscitation improved the success of resuscitation compared to cooling with cold saline infusion.