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Elevation of the head and expiratory negative airway pressure (ENAP) ventilation can both significantly alter cardiovascular hemodynamics. The impact of head-up tilt (HUT) position on mechanically regulated ENAP ventilation-induced hemodynamics was assessed in microminipigs under halothane anesthesia (n = 4) in the absence and presence of adrenergic blockade. Supine ENAP ventilation increased cardiac output, but decreased mean right atrial, systolic pulmonary arterial, and mean left atrial pressures without significantly altering heart rate or aortic pressure. With HUT, the magnitude of ENAP ventilation-induced reduction in right and left atrial pressures was attenuated. HUT minimally altered ENAP ventilation-induced increase in cardiac output and reduction in pulmonary arterial systolic pressure. In addition, with up to 10 cm of HUT there was a significant increase in mean right atrial pressure with and without the ENAP ventilation, whereas HUT did not alter the other hemodynamic variables irrespective of ENAP ventilation. These observations suggest that head elevation augments venous return from the brain irrespective of the ENAP ventilation. Additional studies with pharmacological adrenergic blockade revealed that ENAP ventilation-induced increases in cardiac output and decreases in pulmonary systolic pressure were minimally altered by sympathetic nerve activity, irrespective of the head position. However, the observed ENAP ventilation-induced decreases in right and left atrial pressures were largely dependent upon adrenergic activity. These experimental findings may provide insight into future clinical application of HUT and ENAP for patients with head injury and hypotension.

Motion of mitral valve during cardiac massage was examined using beagle dogs with ventricular fibrillation (n=4). Active compression-decompression cardiac massage (ACD-CM) exhibited greater peak aortic pressure than standard cardiac massage (S-CM), reverse of which was true for peak pulmonary capillary wedge pressure in each animal. Accordingly, peak aortic pressure was greater than peak pulmonary capillary wedge pressure with ACD-CM, whereas its reverse was true with S-CM. Transesophageal echocardiography revealed that mitral valve was incompletely closed with S-CM with showing regurgitation. The valve was more effectively closed during ACD-CM. These results indicate that effective closure of mitral valve during cardiac massage may increase forward blood flow, supporting "cardiac pump theory" rather than "thoracic pump theory" as a principle in dogs.

Aim The optimal head and thorax position after return of spontaneous circulation (ROSC) following cardiac arrest (CA) is unknown. This study examined whether head and thorax elevation post-ROSC is beneficial, in a porcine model. Methods Protocol A: 40 kg anesthetized pigs were positioned flat, after 7.75 min of untreated CA the heart and head were elevated 8 and 12 cm, respectively, above the horizontal plane, automated active compression decompression (ACD) plus impedance threshold device (ITD) CPR was started, and 2 min later the heart and head were elevated 10 and 22 cm, respectively, over 2 min to the highest head up position (HUP). After 30 min of CPR pigs were defibrillated and randomized 10 min later to four 5-min epochs of HUP or flat position. Multiple physiological parameters were measured. In Protocol B, after 6 min of untreated VF, pigs received 6 min of conventional CPR flat, and after ROSC were randomized HUP versus Flat as in Protocol A. The primary endpoint was cerebral perfusion pressure (CerPP). Multivariate analysis-of-variance (MANOVA) for repeated measures was used. Data were reported as mean ± SD. Results In Protocol A, intracranial pressure (ICP) (mmHg) was significantly lower post-ROSC with HUP (9.1 ± 5.5) versus Flat (18.5 ± 5.1) (p Conclusion Post-ROSC head and thorax elevation in a porcine model of cardiac arrest resulted in higher CerPP and lower ICP values, regardless of VF duration or CPR method. IACUC Protocol Number 19-09.

Survival after out-of-hospital cardiac arrest (OHCA) remains poor. A physiologically distinct cardiopulmonary resuscitation (CPR) strategy consisting of (1) active compression-decompression CPR and/or automated CPR, (2) an impedance threshold device, and (3) automated controlled elevation of the head and thorax (ACE) has been shown to improve neurological survival significantly versus conventional (C) CPR in animal models. This resuscitation device combination, termed ACE-CPR, is now used clinically.To assess the probability of OHCA survival to hospital discharge after ACE-CPR versus C-CPR.As part of a prospective registry study, 227 ACE-CPR OHCA patients were enrolled 04/2019-07/2020 from 6 pre-hospital systems in the United States. Individual C-CPR patient data (n = 5196) were obtained from three large published OHCA randomized controlled trials from high-performing pre-hospital systems. The primary study outcome was survival to hospital discharge. Secondary endpoints included return of spontaneous circulation (ROSC) and favorable neurological survival. Propensity-score matching with a 1:4 ratio was performed to account for imbalances in baseline characteristics.Irrespective of initial rhythm, ACE-CPR (n = 222) was associated with higher adjusted odds ratios (OR) of survival to hospital discharge relative to C-CPR (n = 860), when initiated in11 min (3.28, 95 % confidence interval [CI], 1.55-6.92) and 18 min (1.88, 95 % CI, 1.03-3.44) after the emergency call, respectively. Rapid use of ACE-CPR was also associated with higher probabilities of ROSC and favorable neurological survival.Compared with C-CPR controls, rapid initiation of ACE-CPR was associated with a higher likelihood of survival to hospital discharge after OHCA.

Aim Controlled sequential elevation of the head and thorax (CSE) during active compression–decompression (ACD) CPR with an impedance threshold device (ITD) augments cerebral (CerPP) and coronary (CorPP) perfusion pressures. The optimal CSE is unknown. Methods After 8 minutes of untreated VF, 40 kg anesthetized female pigs were positioned on a customized head and thorax elevation device (CED). After 2 min of automated ACD + ITD-16 CPR to ‘prime the system’, 12 pigs were randomized to CSE to the highest CED position over 4-min or 10-min. The primary outcome was CerPP after 7 minutes of CPR. Secondarily, 24-sec (without a priming step) and 2-min CSE times were similarly tested (n = 6 group) in a non-randomized order. Values expressed as mean ± SD. Results After 7 min of CPR, CerPPs were significantly higher in the 4-min vs 10-min CSE groups (53 ± 14.4 vs 38.5 ± 3.6 mmHg respectively, p = 0.03) whereas CorPP trended higher. The 4-min CSE group achieved 50% of baseline (50% BL) CerPP faster than the 10-min group (2.5 ± 1.2 vs 6 ± 3.1 minutes, p = 0.03). CerPP values in the 2-min and 4-min CSE groups were significantly higher than in the 24-sec group. With CSE, CerPPs and CorPPs increased over time in all groups. Conclusions By optimizing controlled sequential elevation timing, CerPP values achieved 50% of baseline within less than 2.5 minutes and >80% of baseline after 7 minutes of CPR. This novel CPR approach rapidly restored CerPPs to near normal values non-invasively and without vasopressors.

Introduction: Survival rates after out-of-hospital cardiac arrest (OHCA) remain poor with widespread use of conventional (C) CPR. Based on pre-clinical studies showing improved cerebral flow and neurologically-intact survival, a FDA approved automated Head Up Positioning (AHUP) device for CPR was developed for use with an impedance threshold device (ITD), and manual and/or automated suction cup-based CPR. A prospective observational IRB approved registry was created to track use and clinical outcomes with this AHUP device based bundle. Hypothesis: Faster time to use of an AHUP CPR bundle improves survival to hospital discharge after OHCA versus historical controls treated with C-CPR. Methods: Registry patients from sites routinely recording time from 911 call to AHUP device placement (T 911 ) were included. C-CPR controls were from 3 prior randomized prospective CPR trials: 1) Resuscitation Outcomes Consortium Prehospital Resuscitation using an IMpedance valve and Early versus Delayed (ROC PRIMED) Study, 2) Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study (ROC-ALPS), 3) The ResQTrial. Propensity score analysis was performed using logistic regression for baseline characteristics including age, sex, witnessed arrest, bystander CPR, shockable rhythm, and time to first responder CPR. Each AHUP patient was matched with up to 4 C-CPR patients. Results: Of 11 U.S. sites reporting AHUP CPR outcomes, 6 had time from 911 call to AHUP device placement recorded (n = 227). The model yielded a c-statistic of 0.76. Stratified by T 911 , the odds of survival with AHUP CPR were significantly higher than with C-CPR between T 911 < 7 minutes (OR 4.57, 95% CI 1.3-16.0) and T 911 < 15 minutes (OR 2.01, 95% CI 1.1-3.8). There was a time dependent effect of AHUP device placement on survival (See Figure). Conclusions: More rapid initiation of an AHUP CPR bundle resulted in improved survival to hospital discharge versus historical controls treated with C-CPR in OHCA.

Introduction: Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest but the optimal target to reach for mean arterial pressure (MAP) remains to be determined. Hypothesis: We hypothesized that MAP levels modify cerebral hemodynamics during E-CPR. Accordingly, we tested two MAP targets (65-75 vs 80-90 mmHg) in a porcine model of E-CPR. Methods: Pigs were anesthetized and instrumented for the evaluation of cerebral and systemic hemodynamics. They were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Electric attempts of defibrillation were then delivered until resumption of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min with a standardized volume expansion in both groups. The dose of epinephrine was set to reach either a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120 min after ROSC. Results: Six animals were included in both groups. After cardiac arrest, MAP was maintained at the expected level (Figure). During E-CPR, high MAP transiently improved carotid blood flow as compared to standard MAP. This blood flow progressively decreased after ROSC in high vs standard MAP, while intra-cranial pressure increased. Interestingly, this was associated with a significant decrease in cerebral oxygen consumption (26±8 vs 54±6 L O 2 /min/kg at 120 min after ROSC, respectively; p Conclusion: Increasing MAP above 80 mmHg with epinephrine aggravates cerebral hemodynamics after E-CPR. Figure: Mean arterial pressure (MAP), cerebral blood flow and oxygen consumption (*, p

Objectives Resuscitation in the Head Up position improves outcomes in animals treated with active compression decompression cardiopulmonary resuscitation and an impedance threshold device (ACD + ITD CPR). We assessed impact of time to deployment of an automated Head Up position (AHUP) based bundle of care after out-of-hospital cardiac arrest on return of spontaneous circulation (ROSC). Methods Observational data were analyzed from a patient registry. Patients received treatment with 1) ACD + and/or automated CPR 2) an ITD and 3) an AHUP device. Probability of ROSC (ROSCprob) from the 9-1-1 call to AHUP device placement was assessed with a restricted cubic spline model and linear regression. Results Of 11 sites, 6 recorded the interval from 9-1-1 to AHUP device (n = 227). ROSCprob for all rhythms was 34%(77/227). Median age (range) was 66 years (19-101) and 68% men. The ROSCprob for shockable rhythms was 47%(18/38). Minutes from 9-1-1 to AHUP device (median, range) varied between sites: 1) 6.4(4,15), 2) 8.0(5,19), 3) 9.9(4, 12), 4) 14.1(6, 36), 5) 15.9(6, 34), 6) 19.0(8, 38),(p = 0.0001). ROSCprob also varied; 1) 55.1%(16/29), 2) 60%(3/5), 3) 50%(3/6), 4) 22.7%(17/75), 5) 26.4%(9/34), and 6) 37.1%(29/78), (p = 0.019). For all rhythms between 4-12 minutes (n = 85), ROSCprob declined 5.6% for every minute elapsed (p = 0.024). For shockable rhythms, between 6-15 minutes (n = 23), ROSCprob declined 9.0% for every minute elapsed (p = 0.006). Conclusions Faster time to deployment of an AHUP based bundle of care is associated with higher incidence of ROSC. This must be considered when evaluating and implementing this bundle.

We studied the impact of mechanically regulated, expiratory negative airway pressure (ENAP) ventilation on pulmonary and systemic circulation including its mechanisms and potential applications. Microminipigs weighing about 10 kg were anesthetized (n = 5). First, hemodynamic variables were evaluated without and with ENAP to approximately −16 cmH2O. ENAP significantly increased heart rate and cardiac output, but decreased right atrial, pulmonary arterial and pulmonary capillary wedge pressures. Second, the evaluation was repeated following pharmacological adrenergic blockade, modestly blunting ENAP effects. Third, fluvoxamine (10 mg/kg) was intravenously administered to intentionally induce cardiovascular collapse in the presence of adrenergic blockade. ENAP was started when systolic pressure was 50 mmHg (n = 2): both animals fully recovered without neurological deficit, whereas without ENAP both animals died of cardiac arrest (n = 2). ENAP may become an innovative treatment for drug-induced cardiovascular collapse.

Traumatic brain injury (TBI) is associated with increased morbidity and mortality in civilian trauma and battlefield settings. It has been classified across a continuum of dysfunctions, with as much as 80% to 90% of cases diagnosed as mild to moderate in combat casualties. In this report, a framework is presented that focuses on the potential benefits for acute noninvasive treatment of reduced cerebral perfusion associated with mild TBI by harnessing the natural transfer of negative intrathoracic pressure during inspiration. This process is known as intrathoracic pressure regulation (IPR) therapy, which can be applied by having a patient breath against a small inspiratory resistance created by an impedance threshold device. Intrathoracic pressure regulation therapy leverages two fundamental principles for improving blood flow to the brain: (1) greater negative intrathoracic pressure enhances venous return, cardiac output, and arterial blood pressure; and (2) lowering of intracranial pressure provides less resistance to cerebral blood flow. These two effects work together to produce a greater pressure gradient that results in an improvement in cerebral perfusion pressure. In this way, IPR therapy has the potential to counter hypotension and hypoxia, potentially significant contributing factors to secondary brain injury, particularly in conditions of multiple injuries that include severe hemorrhage. By implementing IPR therapy in patients with mild-to-moderate TBI, a potential exists to provide early neuroprotection at the point of injury and a bridge to more definitive care, particularly in settings of prolonged delays in evacuation such as those anticipated in future multidomain operations. LEVEL OF EVIDENCE Report.

BACKGROUND Effects of rapid electrical defibrillation and β-blockade on coronary ischemia/reperfusion-induced ventricular fibrillation (VF) during cardiopulmonary resuscitation (CPR) remain unknown.Methods and Results:After induction of VF by 30 min of ischemia followed by reperfusion, animals were treated with defibrillation alone (Group A, n=13), 2 min of open-chest cardiac massage followed by defibrillation (Group B, n=11), or the same therapy to Group B with propranolol (1 mg/kg, i.v.) treatment before ischemia/reperfusion (Group C, n=11). If return of spontaneous circulation (ROSC) was not attained, each therapy was repeated ≤3 times (Set-1). When ROSC was not obtained within Set-1, cardiac massage was applied to all animals followed by defibrillation, which was repeated ≤3 times (Set-2). ROSC after Set-1 was 8% in Group A, 82% in Group B and 82% in Group C, whereas that after Set-2 was 62% in Group A, 100% in Group B and 82% in Group C. Each animal with ROSC in Groups A (n=8) and B (n=11) showed sinus rhythm, whereas those in Group C (n=9) had sinus rhythm (n=5), atrial fibrillation (n=1), accelerated idioventricular rhythm (n=2) and atrioventricular block (n=1). Post ROSC heart rate and mean arterial pressure were significantly lower in Group C. CONCLUSIONS Cardiac massage increased the likelihood of ROSC vs. rapid defibrillation, but β-blocker pretreatment may worsen hemodynamics and electrical stability after ROSC.

Background Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65–75 vs 80–90 mmHg) in a porcine model. Methods Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65–75 vs 80–90 mmHg, respectively). Animals were followed during 120-min after ROSC. Results Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC. Conclusions During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.

We studied the impact of mechanically regulated, expiratory negative airway pressure (ENAP) ventilation on pulmonary and systemic circulation including its mechanisms and potential applications. Microminipigs weighing about 10 kg were anesthetized (n = 5). First, hemodynamic variables were evaluated without and with ENAP to approximately -16 cmH

Introduction: Spontaneous gasping (SG) during cardiac arrest is associated with favorable neurological outcomes. SG lowers intrathoracic pressure (ITP), enhancing flow of respiratory gases to the lungs and venous blood to the heart, while simultaneously lowering intracranial pressure (ICP). The impact of SG on regional cerebral oximetry (rSO2) is unknown. Hypothesis: During untreated ventricular fibrillation (VF), SG will increase rSO2 until the gasping effort declines. Methods: Swine (~40 kg) were intubated and anesthetized with isoflurane. After 8 min of untreated VF, conventional mechanical CPR at 100 compressions/min was performed. Intrathoracic pressure (ITP), mean aortic pressure (MAP), ICP, right atrial pressure (RAP) and calculated cerebral perfusion pressure (CerPP) were measured continuously. rSO2 was measured continuously with near-infrared spectroscopy (Equanox 7600, Nonin Medical). These parameters were assessed before and during SG, and during CPR. Data are expressed as mean ± SD. A paired Student’s t- test was used. Results: SG occurred in 19/22 pigs during untreated VF, with 9.2 ± 4.3 gasps/pig. For pigs that gasped, the individual gasp duration was 1.74 ± 0.52 sec and the maximum negative ITP (mmHg) was -3.24 ± 1.93 mmHg. rSO2 increased in 9/19 (47%) pigs from 54.7% ± 4.1 to 57.8% ± 4.8 during SG (p Conclusions: rSO2 values increased in nearly half of animals with SG. This increase in rSO2 with SG was equal to the level of rSO2 achieved after 1 minute of CPR. Further study is warranted to determine potential prognostic and therapeutic implications of SG-induced increases rSO2 during cardiac arrest.

Aim of the study Controlled sequential elevation of the head and thorax (CSE) during active compression decompression (ACD) cardiopulmonary resuscitation (CPR) with an impedance threshold device (ITD) has been shown to increase cerebral perfusion pressure and cerebral blood flow in previous animal studies as compared to the traditional supine position. The potential for this novel bundled treatment strategy to improve survival with intact neurological function is unknown. Methods Female farm pigs were sedated, intubated, and anesthetized. Central arterial and venous access were continuously monitored. Regional brain tissue perfusion (CerO2) was also measured transcutaneous. Ventricular fibrillation (VF) was induced and untreated for 10 min. Pigs were randomized to (1) Conventional CPR (C-CPR) flat or (2) ACD + ITD CSE CPR that included 2 min of ACD + ITD with the head and heart first elevated 10 and 8 cm, and then gradual elevation over 2 min to 22 and 9 cm, respectively. After 19 min of CPR, pigs were defibrillated and recovered. A veterinarian blinded to the intervention assessed cerebral performance category (CPC) at 24 h. A neurologically intact outcome was defined as a CPC score of 1 or 2. Categorical outcomes were analyzed by Fisher's exact test and continuous outcomes with an unpaired student's t-test. Results In 16 animals, return of spontaneous circulation rate was 8/8 (100%) with ACD + ITD CSE and 3/8 (25%) for C-CPR (p = 0.026). For the primary outcome of neurologically intact survival, 6/8 (75%) pigs had a CPC score 1 or 2 with ACD + ITD CSE versus 1/8 (12.5%) with C-CPR (p = 0.04). Coronary perfusion pressure (mmHg, mean ± SD) was higher with CSE at 18 min (41 ± 24 versus 10 ± 5, p = 0.004). rSO2 (%, mean ± SD) and ETCO2 (mmHg, mean ± SD) values were higher at 18 min with CSE (32 ± 9 versus 17 ± 2, p = 0.01, and 55 mmHg ± 10 versus 21 mmHg ± 4, p Conclusions The novel bundled resuscitation approach of CSE with ACD + ITD CPR increased favorable neurological survival versus C-CPR in a swine model of cardiac arrest.

Study objective Ventricular paced rhythm is thought to obscure the electrocardiographic diagnosis of acute coronary occlusion myocardial infarction. Our primary aim was to compare the sensitivity of the modified Sgarbossa criteria (MSC) to that of the original Sgarbossa criteria for the diagnosis of occlusion myocardial infarction in patients with ventricular paced rhythm. Methods In this retrospective case-control investigation, we studied adult patients with ventricular paced rhythm and symptoms of acute coronary syndrome who presented in an emergency manner to 16 international cardiac referral centers between January 2008 and January 2018. The occlusion myocardial infarction group was defined angiographically as thrombolysis in myocardial infarction grade 0 to 1 flow or angiographic evidence of coronary thrombosis and peak cardiac troponin I ≥10.0 ng/mL or troponin T ≥1.0 ng/mL. There were 2 control groups: the "non-occlusion myocardial infarction-angio" group consisted of patients who underwent coronary angiography for presumed type I myocardial infarction but did not meet the definition of occlusion myocardial infarction; the "no occlusion myocardial infarction" control group consisted of randomly selected emergency department patients without occlusion myocardial infarction. Results There were 59 occlusion myocardial infarction, 90 non-occlusion myocardial infarction-angio, and 102 no occlusion myocardial infarction subjects (mean age, 72.0 years; 168 [66.9%] men). For the diagnosis of occlusion myocardial infarction, the MSC were more sensitive than the original Sgarbossa criteria (sensitivity 81% [95% confidence interval [CI] 69 to 90] versus 56% [95% CI 42 to 69]). Adding concordant ST-depression in V4 to V6 to the MSC yielded 86% (95% CI 75 to 94) sensitivity. For the no occlusion myocardial infarction control group of ED patients, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 96% (95% CI 90 to 99) versus 97% (95% CI 92 to 99); negative likelihood ratio (LR) 0.19 (95% CI 0.11 to 0.33) versus 0.45 (95% CI 0.34 to 0.65); and positive LR 21 (95% CI 7.9 to 55) versus 19 (95% CI 6.1 to 59). For the non-occlusion myocardial infarction-angio control group, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 84% (95% CI 76 to 91) versus 90% (95% CI 82 to 95); negative LR 0.22 (95% CI 0.13 to 0.38) versus 0.49 (95% CI 0.35 to 0.66); and positive LR 5.2 (95% CI 3.2 to 8.6) versus 5.6 (95% CI 2.9 to 11). Conclusion For the diagnosis of occlusion myocardial infarction in the presence of ventricular paced rhythm, the MSC were more sensitive than the original Sgarbossa criteria; specificity was high for both rules. The MSC may contribute to clinical decisionmaking for patients with ventricular paced rhythm.

Introduction Cerebral blood flow during cardiopulmonary resuscitation (CPR) is a major neuroprognostic factor although not clinically feasible for routine assessment and monitoring. In this context, a surrogate marker for cerebral perfusion during CPR is highly desirable. Yet, cerebral blood flow hemodynamic determinants remain poorly understood and their significance might be altered by changes in head positioning such as flat, head up, and head down during CPR. Hypothesis We hypothesized that routinely measured hemodynamic parameters would correlate with cerebral brain flow during CPR, independently of the head position. Methods Associations between cerebral blood flow, measured using microsphere techniques, and hemodynamic parameters were studied from two prior publications. Eight pigs receiving CPR with an automated device and an impedance threshold device in the flat or supine, whole body head down and whole body head up tilt positions were analysed for the derivation sample. Relevant associations were examined for consistency in an external validation sample consisting of 18 pigs randomized to supine position versus head and torso elevation. Results After adjusting for position, arterial blood pressure and cerebral perfusion pressure during decompression were significantly associated with cerebral blood flow, in the derivation and the external validation samples. No significant associations were found between cerebral blood flow during CPR and right atrial pressure, intracranial pressure, end tidal CO2, carotid blood flow, and coronary perfusion pressure in the derivation sample. Conclusion Decompression arterial blood pressure and cerebral perfusion pressure are relevant candidate surrogate markers for cerebral blood flow during CPR, independently of head position.

Report, One of the most effective ways to increase the cardiopulmonary resuscitation (CPR) rate of lay rescuers is through education of school children. We developed a learning tool called “Dock-kun" to help school children understand and master high-quality manual cardiac massage. With “Dock-kun," school children can visually learn about the physiology of CPR and how to correctly perform this life-saving technique by checking the amount of water, a surrogate for blood, being pumped out of the model heart and sucked back into the heart with each compression-decompression cycle. The forward flow was maximized when the high-quality cardiac massage was performed with a depth of 4.5-5.0 cm and a rate of 105-110 compressions per minute. The real-time flow of “water" and feedback to the rescuer provide a means for school children to learn high-quality cardiac massage technique and understand its related mechanophysiology. Workshops using this new educational tool will greatly contribute to widespread knowledge of the high-quality cardiac massage among school children.

Background The prevalence of coronary artery disease (CAD) among patients with refractory out-of-hospital (OH) ventricular fibrillation (VF)/ventricular tachycardia (VT) cardiac arrest is unknown. Objectives The goal of this study was to describe the prevalence and complexity of CAD and report survival to hospital discharge in patients experiencing refractory VF/VT cardiac arrest treated with a novel protocol of early transport to a cardiac catheterization laboratory (CCL) for extracorporeal life support (ECLS) and revascularization. Methods Between December 1, 2015, and December 1, 2016, consecutive adult patients with refractory OH VF/VT cardiac arrest requiring ongoing cardiopulmonary resuscitation were transported by emergency medical services to the CCL. ECLS, coronary angiography, and percutaneous coronary intervention were performed, as appropriate. Functionally favorable survival to hospital discharge (Cerebral Performance Category 1 or 2) was determined. Outcomes in a historical comparison group were also evaluated. Results Sixty-two (86%) of 72 transported patients met emergency medical services transport criteria. Fifty-five (89%) of the 62 patients met criteria for continuing resuscitation on CCL arrival; 5 had return of spontaneous circulation, 50 received ECLS, and all 55 received coronary angiography. Forty-six (84%) of 55 patients had significant CAD, 35 (64%) of 55 had acute thrombotic lesions, and 46 (84%) of 55 had percutaneous coronary intervention with 2.7 ± 2.0 stents deployed per patient. The mean SYNTAX score was 29.4 ± 13.9. Twenty-six (42%) of 62 patients were discharged alive with Cerebral Performance Category 1 or 2 versus 26 (15.3%) of 170 in the historical comparison group (odds ratio: 4.0; 95% confidence interval: 2.08 to 7.7; p Conclusions Complex but treatable CAD was prevalent in patients with refractory OH VF/VT cardiac arrest who also met criteria for continuing resuscitation in the CCL. A systems approach using ECLS and reperfusion seemed to improve functionally favorable survival.

Chest compliance plays a fundamental role in the generation of circulation during cardiopulmonary resuscitation (CPR). To study potential changes in chest compliance over time, anterior posterior (AP) chest height measurements were performed on newly deceased (never frozen) human cadavers during CPR before and after 5min of automated CPR. We tested the hypothesis that after 5min of CPR chest compliance would be significantly increased.Static compression (30, 40, and 50kg) and decompression forces (-10, -15kg) were applied with a manual ACD-CPR device (ResQPUMP, ZOLL) before and after 5min of automated CPR. Lateral chest x-rays were obtained with multiple reference markers to assess changes in AP distance.In 9 cadavers, changes (mean±SD) in the AP distance (cm) during the applied forces were 2.1±1.2 for a compression force of 30kg, 2.9±1.3 for 40kg, 4.3±1.0 for 50kg, 1.0±0.8 for a decompression force of -10kg and 1.8±0.6 for -15kg. After 5min of automated CPR, AP excursion distances were significantly greater (p0.05). AP distance increased to 3.7±1.4 for a compression force of 30kg, 4.9±1.6 for 40kg, 6.3±1.9 for 50kg, 2.3±0.9 for -10kg of lift and 2.7±1.1 for -15kg of lift.These data demonstrate chest compliance increases significantly over time as demonstrated by the significant increase in the measured AP distance after 5min of CPR. These findings suggest that adjustments in compression and decompression forces may be needed to optimize CPR over time.

Background Potential cardiovascular benefits of precordial percussion pacing (PPP) during cardiac standstill are unknown.Methods and Results:A cardiac standstill model in amicrominipigwas created by inducing complete atrioventricular block with a catheter ablation technique (n=7). Next, the efficacy of cardiopulmonary resuscitation by standard chest compressions (S-CPR), PPP and ventricular electrical pacing in this model were analyzed in series (n=4). To assess the mechanism of PPP, a non-selective, stretch-activated channel blocker, amiloride, was administered during PPP (n=3). Peak systolic and diastolic arterial pressures during S-CPR, PPP and ventricular electrical pacing were statistically similar. However, the duration of developed arterial pressure with PPP was comparable to that with ventricular electrical pacing, and significantly greater than that with S-CPR. Amiloride decreased the induction rate of ventricular electrical activity by PPP in a dose-related manner. Each animal survived without any neurological deficit at 24, 48 h and 1 week, even with up to 2 h of continuous PPP. Conclusions In amicrominipigmodel of cardiac standstill, PPP can become a novel means to significantly improve physiological outcomes after cardiac standstill or symptomatic bradyarrhythmias in the absence of cardiac pacing. Activation of the non-selective stretch-activated channels may mediate some of the mechanophysiological effects of PPP. Further study of PPP by itself and together with S-CPR is warranted using cardiac arrest models of atrioventricular block and asystole.

Introduction: Controlled sequential elevation of the head and thorax (CSE) during active compression-decompression (ACD) CPR with an impedance threshold device (ITD) has previously resulted in sustained nearly normal cerebral perfusion pressures (CerPP) of 75 mmHg. However, the optimal speed of CSE remains unknown. It is also unknown if some CPR is needed to ‘prime the system’ prior to maximal CSE. Hypothesis: An optimized CSE will achieve 50% of baseline (50% BL) CerPP in Methods: Female farm pigs were intubated and anesthetized. Central vascular and intracranial access were obtained. After 8 min of untreated ventricular fibrillation, pigs were placed in a customized elevation device (CED). After 2 min of ACD+ITD CPR at the lowest CED level to prime the circulation, pigs were randomized to CSE over 1) 4-min or 2) 10-min until the CED reached its highest level. ACD ITD CPR was performed for a total of 19 minutes. Based upon initial results, two additional groups of pigs were studied: one with a CSE over 2-min after the 2 min ‘priming’ step, and the other with CSE over 24-sec without priming. The primary outcome was time in minutes to achieve 50% BL of CerPP values. Results: There were six pigs per study group (4-min, 10-min, 2-min and 24-sec). The 4-min CSE group achieved 50% BL CerPP faster (min ± SD) than the 10-min CSE group (2.53 ± 1.26 vs 5.98 ± 3.16 , p=0.04, Figure 1). The 2-min CSE group CerPP was similar to the 4-min group (2.36 ± 2.18, p=0.92). The time to 50% BL CerPP trended 4 min faster in the 2-min CSE group versus the 24-sec CSE group (6.6 ± 6.73, p=0.16), as shown in the figure. With CSE, CerPPs increased over time in all groups. All pigs were resuscitated. Conclusions: A 50% BL CerPP value was achieved in

Aim of the study Negative intrathoracic pressure (ITP) during the decompression phase of cardiopulmonary resuscitation (CPR) is essential to refill the heart, increase cardiac output, maintain cerebral and coronary perfusion pressures, and improve survival. In order to generate negative ITP, an airway seal is necessary. We tested the hypothesis that some supraglottic airway (SGA) devices do not seal the airway as well the standard endotracheal tube (ETT). Methods Airway pressures (AP) were measured as a surrogate for ITP in seven recently deceased human cadavers of varying body habitus. Conventional manual, automated, and active compression-decompression CPR were performed with and without an impedance threshold device (ITD) in supine and Head Up positions. Positive pressure ventilation was delivered by an ETT and 5 SGA devices tested in a randomized order in this prospective cross-over designed study. The primary outcome was comparisons of decompression AP between all groups. Results An ITD was required to generate significantly lower negative ITP during the decompression phase of all methods of CPR. SGAs varied in their ability to support negative ITP. Conclusion In a human cadaver model, the ability to generate negative intrathoracic pressures varied with different SGAs and an ITD regardless of the body position or CPR method. Differences in SGAs devices should be strongly considered when trying to optimize cardiac arrest outcomes, as some SGAs do not consistently develop a seal or negative intrathoracic pressure with multiple different CPR methods and devices.

Aim of the Study Elevation of the head and thorax (HUP) during cardiopulmonary resuscitation (CPR) has been shown to double brain blood flow with increased cerebral perfusion pressures (CerPP) after active compression-decompression (ACD) CPR with an impedance threshold device (ITD). However, the optimal angle for HUP CPR is unknown. Methods In Study A, different angles were assessed (20°, 30°, 40°), each randomized over 5-min periods of ACD + ITD CPR, after 8 min of untreated ventricular fibrillation in an anesthetized swine model. Based upon Study A, Study B was performed, where animals were randomized to 1 of 2 sequences: 20°, 30°, 40° or 40°, 30°, 20° with a similar protocol. The primary endpoint was CerPP for both studies. Results In Study A, no optimal HUP angle was observed in 18 pigs. CerPPs for 30° and 40° (mmHg, mean ± SD) were equivalent (44 ± 22 and 47 ± 26, p = 0.18). However, CerPP appeared higher when 40° HUP was performed during the last 5-min of CPR, suggestive of a sequence effect. For Study B, after 17 min of CPR, CerPP (mmHg) were higher with the 20°, 30°, 40° sequence: 60 ± 17 versus 33 ± 18 (p = 0.035). Conclusions No optimal HUP CPR angle was observed. However, controlled progressive elevation of the head and thorax during CPR is more beneficial than an absolute angle or height to maximize CerPP. Further studies are needed to determine the optimal rate of rise during HUP ACD + ITD CPR. Institutional Protocol Number 17-06.

Objective Ischemic postconditioning (PC) using three intentional pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. We hypothesized PC, performed during basic life support (BLS) in the absence of epinephrine, would reduce reperfusion injury and enhance 24h functional recovery. Design Prospective animal investigation. Setting Animal laboratory Subjects Female farm pigs ( n =46, 39±1kg). Interventions Protocol A: After 12min of ventricular fibrillation (VF), 28 pigs were randomized to four groups: (A) Standard CPR (SCPR), (B) active compression-decompression CPR with an impedance threshold device (ACD-ITD), (C) SCPR+PC (SCPR+PC) and (D) ACD-ITD CPR+PC. Protocol B: After 15min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD+PC. The BLS duration was 2.75min in Protocol A and 5min in Protocol B. Following BLS, up to three shocks were delivered. Without return of spontaneous circulation (ROSC), CPR was resumed and epi (0.5mg) and defibrillation delivered. The primary end point was survival without major adverse events. Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean±SEM. Measurements and Main Results Protocol A: ACD-ITD+PC (group D) improved coronary perfusion pressure after 3min of BLS versus the three other groups (28±6, 35±7, 23±5 and 47±7 for groups A, B, C, D respectively, p =0.05). There were no significant differences in 24h survival between groups. Protocol B LVEF 4h post ROSC was significantly higher with ACD-ITD+PC vs ACD-ITD alone (52.5±3% vs. 37.5±6.6%, p =0.045). Survival rates were significantly higher with ACD-ITD+PC vs. ACD-ITD alone ( p =0.027). Conclusions BLS using ACD-ITD+PC reduced post resuscitation cardiac dysfunction and improved functional recovery after prolonged untreated VF in pigs. Protocol number 12-11.

Survival rates after cardiac arrest have shown minimal improvement in the last 60 years. However, in some forward-thinking cities and hospitals, out-of and in-hospital cardiac arrest survival rates exceed 20% and 40% respectively. These beacons of hope can enlighten us, providing a clearer vision of what it takes to provide Ideal cardiopulmonary resuscitation. To make progress in a field that has seemingly stagnated for too many decades, we must be open to new ideas and develop bundles of care that work in communities with varying EMS systems and various existing infrastructure to bring the best practices to the rest of the country.

Background: Elevation of the head and thorax (HUP) during cardiopulmonary resuscitation (CPR) has been shown to result in a doubling of brain blood flow with higher Cerebral Perfusion Pressures (CerPP) after prolonged active compression-decompression (ACD) CPR with an impedance threshold device (ITD). However, the optimal angle and speed of elevation are unknown. Methods: In study A, in an anesthetized female 40 kg pig model of untreated ventricular fibrillation for 8 min, different HUP angles were assessed (20°, 30°, 40°) in a randomized manner each over a 5-minute periods of ACD+ITD CPR. Based upon study A results, study B was performed, wherein animals were randomized to the two following sequences: 20°, 30°, 40° or 40°, 30°, 20° using the same protocol. The primary endpoint was mean ± SD CerPP (mmHg) for both studies. Results: In study A, 18 pigs were studied. Overall, there was no optimal HUP angle: CerPP was 36 ± 19 for 20°, 42 ± 21 for 30°, and 44 ± 27 for 40° (p = 0.57). However, CerPPs were higher if 40 o HUP was performed during the last 5 minutes of the resuscitation (77 ± 17), versus 20 o HUP and 30 o HUP (44± 18, p = 0.003), suggestive of a sequence effect. To test this hypothesis, study B then enrolled additional animals to compare two elevation sequences 20°, 30°, 40° (n = 6) or 40°, 30°, 20° (n = 5). At 15 min of CPR, the CerPP for 20°, 30°, 40° group was 60 ± 17 and for 40°, 30°, 20° the CerPP was 23 ± 19 (p = 0.01). CerPPs were higher for the 20°, 30°, 40° group throughout the resuscitation (Figure 1). Coronary perfusion pressure was also significantly higher in the 20°, 30°, 40° group (50 ± 17 mmHg versus 22 ± 16 mmHg, p = 0.036) Conclusions: There did not appear to be an optimal HUP angle during ACD+ITD CPR. By contrast, there was an optimal HUP sequence (20,30,40) that resulted in significantly higher CerPP, suggesting controlled progressive elevation is important when performing HUP CPR as compared to an absolute immediate elevation of the head and thorax.

Aim The objectives were: 1) replicate key elements of Head Up (HUP) cardiopulmonary resuscitation (CPR) physiology in a traditional swine model of ventricular fibrillation (VF), 2) compare HUP CPR physiology in pig cadavers (PC) to the VF model 3) develop a new human cadaver (HC) CPR model, and 4) assess HUP CPR in HC. Methods Nine female pigs were intubated, and anesthetized. Venous, arterial, and intracranial access were obtained. After 6 min of VF, CPR was performed for 2 min epochs as follows: Standard (S)-CPR supine (SUP), Active compression decompression (ACD) CPR + impedance threshold device (ITD-16) CPR SUP, then ACD + ITD HUP CPR. The same sequence was performed in PC 3 h later. In 9 HC, similar vascular and intracranial access were obtained and CPR performed for 1 min epochs using the same sequence as above. Results The mean cerebral perfusion pressure (CerPP, mmHg) was 14.5 ± 6 for ACD + ITD SUP and 28.7 ± 10 for ACD + ITD HUP (p = .007) in VF, −3.6 ± 5 for ACD + ITD SUP and 7.8 ± 9 for ACD + ITD HUP (p = .007) in PC, and 1.3 ± 4 for ACD + ITD SUP and 11.3 ± 5 for ACD + ITD HUP (p = .007) in HC. Mean systolic and diastolic intracranial pressures (ICP) (mmHg) were significantly lower in the ACD + ITD HUP group versus the ACD + ITD SUP group in all three CPR models. Conclusion HUP CPR decreased ICP while increasing CerPP in pigs in VF as well as in PC and HC CPR models. This first-time demonstration of HUP CPR physiology in humans provides important implications for future resuscitation research and treatment.

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Brain injury is a leading cause of death and disability in children and adults in their most productive years. Use of intrathoracic pressure regulation (IPR) to generate negative intrathoracic pressure during the expiratory phase of positive pressure ventilation improves mean arterial pressure and 24-h survival in porcine models of hemorrhagic shock and cardiac arrest and has been demonstrated to decrease intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in these models. Application of IPR for 240 min in a porcine model of intracranial hypertension (ICH) will increase CPP when compared with controls. Twenty-three female pigs were subjected to focal brain injury by insertion of an epidural Foley catheter inflated with 3 mL of saline. Animals were randomized to treatment for 240 min with IPR set to a negative expiratory phase pressure of -12 cmH2O or no IPR therapy. Intracranial pressure, mean arterial pressure, CPP, and cerebral blood flow (CBF) were evaluated. Intrathoracic pressure regulation significantly improved mean CPP and CBF. Specifically, mean CPP after 90, 120, 180, and 240 min of IPR use was 43.7 ± 2.8 mmHg, 44.0 ± 2.7 mmHg, 44.5 ± 2.8 mmHg, and 43.1 ± 1.9 mmHg, respectively; a significant increase from ICH study baseline (39.5 ± 1.7 mmHg) compared with control animals in which mean CPP was 36.7 ± 1.4 mmHg (ICH study baseline) and then 35.9 ± 2.1 mmHg, 33.7 ± 2.8 mmHg, 33.9 ± 3.0 mmHg, and 36.0 ± 2.7 mmHg at 90, 120, 180, and 240 min, respectively (P < 0.05 for all time points). Cerebral blood flow, as measured by an invasive CBF probe, increased in the IPR group (34 ± 4 mL/100 g-min to 49 ± 7 mL/100 g-min at 90 min) but not in controls (27 ± 1 mL/100 g-min to 25 ± 5 mL/100 g-min at 90 min) (P = 0.01). Arterial pH remained unchanged during the entire period of IPR compared with baseline values and control values. In this anesthetized pig model of ICH, treatment with IPR significantly improved CPP and CBF. This therapy may be of clinical value by noninvasively improving cerebral perfusion in states of compromised cerebral perfusion.

To improve the likelihood for survival with favorable neurologic function after cardiac arrest, we assessed a new advanced life support approach using active compression-decompression cardiopulmonary resuscitation plus an intrathoracic pressure regulator.Prospective animal investigation.Animal laboratory.Female farm pigs (n = 25) (39 ± 3 kg).Protocol A: After 12 minutes of untreated ventricular fibrillation, 18 pigs were randomized to group A-3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with standard cardiopulmonary resuscitation; group B-3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator; and group C-3 minutes of basic life support with active compression-decompression cardiopulmonary resuscitation plus an impedance threshold device, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator. Advanced life support always included IV epinephrine (0.05 μg/kg). The primary endpoint was the 24-hour Cerebral Performance Category score. Protocol B: Myocardial and cerebral blood flow were measured in seven pigs before ventricular fibrillation and then following 6 minutes of untreated ventricular fibrillation during sequential 5 minutes treatments with active compression-decompression plus impedance threshold device, active compression-decompression plus intrathoracic pressure regulator, and active compression-decompression plus intrathoracic pressure regulator plus epinephrine.Protocol A: One of six pigs survived for 24 hours in group A versus six of six in groups B and C (p = 0.002) and Cerebral Performance Category scores were 4.7 ± 0.8, 1.7 ± 0.8, and 1.0 ± 0, respectively (p = 0.001). Protocol B: Brain blood flow was significantly higher with active compression-decompression plus intrathoracic pressure regulator compared with active compression-decompression plus impedance threshold device (0.39 ± 0.23 vs 0.27 ± 0.14 mL/min/g; p = 0.03), whereas differences in myocardial perfusion were not statistically significant (0.65 ± 0.81 vs 0.42 ± 0.36 mL/min/g; p = 0.23). Brain and myocardial blood flow with active compression-decompression plus intrathoracic pressure regulator plus epinephrine were significantly increased versus active compression-decompression plus impedance threshold device (0.40 ± 0.22 and 0.84 ± 0.60 mL/min/g; p = 0.02 for both).Advanced life support with active compression-decompression plus intrathoracic pressure regulator significantly improved cerebral perfusion and 24-hour survival with favorable neurologic function. These findings support further evaluation of this new advanced life support methodology in humans.

As most cardiopulmonary resuscitation (CPR) efforts last longer than 15min, the aim of this study was to compare brain blood flow between the Head Up (HUP) and supine (SUP) body positions during a prolonged CPR effort of 15min, using active compression-decompression (ACD) CPR and impedance threshold device (ITD) in a swine model of cardiac arrest.Ventricular fibrillation (VF) was induced in anesthetized pigs. After 8min of untreated VF followed by 2min of ACD-CPR+ITD in the SUP position, pigs were randomized to 18min of continuous ACD-CPR+ITD in either a 30° HUP or SUP position. Microspheres were injected before VF and then 5 and 15min after start of CPR.The mean blood flow (ml/min/g, mean±SD) to the brain after 15min of CPR was 0.42±0.05 in the HUP group (n=8) and 0.21±0.04 SUP (n=10), respectively, (p0.01). The HUP group also had statistically significantly lower intracranial pressures and higher calculated cerebral perfusion pressures after 5, 15, 19 (before adrenaline) and 20 (after adrenaline) minutes of HUT versus SUP CPR.After prolonged ACD-CPR+ITD in the HUP position, brain blood flow was 2-fold higher versus the SUP position. These positive findings provide strong pre-clinical support to proceed with a clinical evaluation of elevation of the head and thorax during ACD-CPR+ITD in humans in cardiac arrest.

Objectives: Intrathoracic pressure regulation therapy (IPRT) has been shown to increase blood pressure in hypotensive patients. The potential value of this therapy in patients with hypotension secondary to trauma with bleeding is not well understood. Hypothesis: We hypothesized that IPRT would non-invasively and safely enhance blood pressure in spontaneously breathing patients with trauma-induced hypotension. Methods: This prospective observational cohort study assessed vital signs from hypotensive patients with a systolic blood pressure (SBP) ≤90 mmHg secondary to trauma treated by pre-hospital emergency medical personnel with IPRT (ResQGARD) in three large US metropolitan areas. Upon determination of hypotension, facemask-based IPRT was initiated as long as bleeding was controlled. Vital signs were recorded before, during, and after IPRT. An increased SBP with IPRT use was the primary study endpoint. Device tolerance and ease of use were also reported. Results: A total of 54 patients with hypotension secondary to trauma were treated from 2009 to 2016. The mean (± SD) SBP increased from 81 ± 12 mmHg to 107 ± 19 with IPRT (p < 0.0001) and mean arterial pressures (MAP) increased from 62 ± 11 mmHg to 82 ± 17 (p < 0.0001). There were no significant changes in mean heart rate or oxygen saturation. Approximately 75% of patients reported moderate to easy tolerance of the device. There were no safety concerns or reported adverse events. Conclusion: In patients with hypotension secondary to trauma IPRT increased blood pressure to levels known to provide near normal or normal vital organ blood flow in the vast majority of patients. Patients were treated safely and not over resuscitated with this intervention. These findings support the use of IPRT to treat trauma-induced hypotension as long as bleeding has been controlled.

Amplitude Spectrum Area (AMSA) values during ventricular fibrillation (VF) correlate with myocardial energy stores and predict defibrillation success. By contrast, end tidal CO2 (ETCO2) values provide a noninvasive assessment of coronary perfusion pressure and myocardial perfusion during cardiopulmonary resuscitation (CPR). Given the importance of the timing of defibrillation shock delivery on clinical outcome, we tested the hypothesis that AMSA and ETCO2 correlate with each other and can be used interchangably to correlate with myocardial perfusion in an animal laboratory preclinical, randomized, prospective investigation. After 6 min of untreated VF, 12 female pigs (32 ± 1 Kg), isoflurane anesthetized pigs received sequentially 3 min periods of standard (S) CPR, S‐CPR+ an impedance threshold device (ITD), and then active compression decompression (ACD) + ITD CPR. Hemodynamic, AMSA, and ETCO2 measurements were made with each method of CPR. The Spearman correlation and Friedman tests were used to compare hemodynamic parameters. ETCO2, AMSA, coronary perfusion pressure, cerebral perfusion pressure were lowest with STD CPR, increased with STD CPR + ITD and highest with ACD CPR + ITD. Further analysis demonstrated a positive correlation between AMSA and ETCO2 (r = 0.37, P = 0.025) and between AMSA and key hemodynamic parameters (P

Background Gasping is a natural reflex that enhances oxygenation and circulation during cardiopulmonary resuscitation (CPR). Objectives This study sought to assess the relationship between gasping during out-of-hospital cardiac arrest and 1-year survival with favorable neurological outcomes. Methods The authors prospectively collected incidence of gasping on all evaluable subjects in a multicenter, randomized, controlled, National Institutes of Health–funded out-of-hospital cardiac arrest clinical trial from August 2007 to July 2009. The association between gasping and 1-year survival with favorable neurological function, defined as a Cerebral Performance Category (CPC) score ≤2 was estimated using multivariable logistic regression. Results The rates of 1-year survival with a CPC score of ≤2 were 5.4% (98 of 1,827) overall, and 20% (36 of 177) and 3.7% (61 of 1,643) for individuals with and without spontaneous gasping or agonal respiration during CPR, respectively. In multivariable analysis, 1-year survival with CPC ≤2 was independently associated with younger age (odds ratio [OR] for 1 SD increment 0.57; 95% confidence interval [CI]: 0.43 to 0.76), gasping during CPR (OR: 3.94; 95% CI: 2.09 to 7.44), shockable initial recorded rhythm (OR: 16.50; 95% CI: 7.40 to 36.81), shorter CPR duration (OR: 0.31; 95% CI: 0.19 to 0.51), lower epinephrine dosage (OR: 0.47; 95% CI: 0.25 to 0.87), and pulmonary edema (OR: 3.41; 95% CI: 1.53 to 7.60). Gasping combined with a shockable initial recorded rhythm had a 57-fold higher OR (95% CI: 23.49 to 136.92) of 1-year survival with CPC ≤2 versus no gasping and no shockable rhythm. Conclusions Gasping during CPR was independently associated with increased 1-year survival with CPC ≤2, regardless of the first recorded rhythm. These findings underscore the importance of not terminating resuscitation prematurely in gasping patients and the need to routinely recognize, monitor, and record data on gasping in all future cardiac arrest trials and registries.

Objective It is unknown whether patient position is associated with the optimal cerebral (CePP) and coronary (CoPP) perfusion pressure. Methods This study utilized a randomized experimental design and anesthetized, intubated and paralyzed female pigs (n = 12) (mean 42, SD 3 kg). After 6 min of untreated ventricular fibrillation, mechanical CPR with was performed for 3 min in 0° supine position. The CPR was then performed for 5 min in a position randomly assigned to either 1) head-up tilt (HUT) by three angles (30°, 45°, or 60°) or 2) head-down tilt (HDT) by three angles (30°, 45°, or 60°) and at 3) supine position between HUT and HDT positions. 4 Pigs were assigned to each angle of HUT or HDT position and 12 pigs were assigned to supine position. CePPs and CoPPs were measured and compared using MIXED procedure with pig as a random effect among angles and compared between angles with Tukey post-hoc analysis. Results With 60°, 45°, 30° head-down, 0° (supine), and 30°, 45°, 60° head-up positioning, mean(SD) CePPs increased consistently as follows: 2.4(0.4), 9.3(1.6), 16.5(1.6), 27.0(1.5), 35.1(0.4), 39.4(0.6), and 39.9(0.3) mmHg, respectively. CoPPs were followings according to same angle: 12.9(2.5), 13.3(2.5), 12.8(0.4), 18.1(0.7), 30.3(0.4), 24.1(0.6), and 26.5(0.9) mmHg, respectively. The CePPs were peak at HUT(45°) and HUT(60°), but CoPP was peak in HUT(30°) and higher than HUT(45°) and HUT(60°). Conclusion Cerebral perfusion pressure during mechanical CPR were similar and highest in the HUT(45° and 60°) positions whereas the peak coronary perfusion pressure was observed with HUT(30°).

Preservation of cardiac output (CO) and pulmonary artery pressure (PAP) is vital to maintaining tissue oxygenation in sepsis. This feasibility study tested the hypothesis that therapeutic intra-thoracic pressure regulation (tIPR), delivered with a novel device, was designed to non-invasively enhance venous return by creating sub-atmospheric intra-thoracic pressure during the expiratory phase of mechanical ventilation, improves CO without fluid resuscitation in a porcine E. coli peritonitis model of sepsis. Seven pigs were intubated, anaesthetized and instrumented with a Swan-Ganz and femoral artery catheter. After a 30 min basal period, a fibrin clot containing 4-5 × 10(9) cfu kg(-1) E. coli O111.B4 was implanted in the peritoneum. One hour after clot implantation, tIPR was utilized for 30 min and then removed from the ventilator circuit for 30 min. This tIPR cycle was repeated 4-times. Changes in haemodynamic parameters were calculated by comparing pre-tIPR values to peak values during tIPR administration. Following peritonitis, tIPR significantly increased the peak cardiac index (mean ± SEM) (14.8 ± 2.6 vs 7.9 ± 2.3 ml kg(-1)) and mean arterial pressure (10.2 ± 1.5 vs 4.9 ± 1.1 mmHg) and simultaneously decreased PAP (-7.7 ± 1.5 vs -2.7 ± 0.8 mmHg). These results support the feasibility of the concept that therapeutic application of negative expiratory pressure may provide a non-invasive and complementary approach to increase cardiac output and organ perfusion in the setting of septic shock.

Background A recent out-of-hospital cardiac arrest (OHCA) clinical trial showed improved survival to hospital discharge (HD) with favorable neurologic function for patients with cardiac arrest of cardiac origin treated with active compression decompression cardiopulmonary resuscitation (CPR) plus an impedance threshold device (ACD+ICD) versus standard (S) CPR. The current analysis examined whether treatment with ACD+ITD is more effective than standard (S-CPR) for all cardiac arrests of non-traumatic origin, regardless of the etiology. Methods This is a secondary analysis of data from a randomized, prospective, multicenter, intention-to-treat, OHCA clinical trial. Adults with presumed non-traumatic cardiac arrest were enrolled and followed for one year post arrest. The primary endpoint was survival to hospital discharge (HD) with favorable neurologic function (Modified Rankin Scale score≤3). Results Between October 2005 and July 2009, 2738 patients were enrolled (S-CPR=1335; ACD+ITD=1403). Survival to HD with favorable neurologic function was greater with ACD+ITD compared with S-CPR: 7.9% versus 5.7%, (OR 1.42, 95% CI 1.04, 1.95, p =0.027). One-year survival was also greater: 7.9% versus 5.7%, (OR 1.43, 95% CI 1.04, 1.96, p =0.026). Nearly all survivors in both groups had returned to their baseline neurological function by one year. Major adverse event rates were similar between groups. Conclusions Treatment of out-of-hospital non-traumatic cardiac arrest patients with ACD+ITD resulted in a significant increase in survival to hospital discharge with favorable neurological function when compared with S-CPR. A significant increase survival rates was observed up to one year after arrest in subjects treated with ACD+ITD, regardless of the etiology of the cardiac arrest.

Aim Chest compressions during cardiopulmonary resuscitation (CPR) increase arterial and venous pressures, delivering simultaneous bidirectional high-pressure compression waves to the brain. We hypothesized that this may be detrimental and could be partially overcome by elevation of the head during CPR. Measurements Female Yorkshire farm pigs (n = 30) were sedated, intubated, anesthetized, and placed on a table able to elevate the head 30° (15 cm) (HUP) and the heart 10° (4 cm) or remain in the supine (SUP) flat position during CPR. After 8 minutes of untreated ventricular fibrillation and 2 minutes of SUP CPR, pigs were randomized to HUP or SUP CPR for 20 more minutes. In Group A, pigs were randomized after 2 minutes of flat automated conventional (C) CPR to HUP (n = 7) or SUP (n = 7) C-CPR. In Group B, pigs were randomized after 2 minutes of automated active compression decompression (ACD) CPR plus an impedance threshold device (ITD) SUP CPR to either HUP (n = 8) or SUP (n = 8). Results The primary outcome of the study was difference in CerPP (mmHg) between the HUP and SUP positions within groups. After 22 minutes of CPR, CerPP was 6 ± 3 mmHg in the HUP versus -5 ± 3 in the SUP (p = 0.016) in Group A, and 51 ± 8 versus 20 ± 5 (p = 0.006) in Group B. Coronary perfusion pressures after 22 minutes were HUP 6 ± 2 vs SUP 3 ± 2 (p = 0.283) in Group A and HUP 32 ± 5 vs SUP 19 ± 5, (p = 0.074) in Group B. In Group B, 6/8 pigs were resuscitated in both positions. No pigs were resuscitated in Group A. Conclusions The HUP position in both C-CPR and ACD + ITD CPR significantly improved CerPP. This simple maneuver has the potential to improve neurological outcomes after cardiac arrest.

OBJECTIVES: Ischemic postconditioning (PC) with “stuttering” reintroduction of blood flow after prolonged ischemia has been shown to offer protection from ischemia reperfusion injury to the myocardium and brain. We hypothesized that four 20-s pauses during the first 3 min of standard CPR would improve post resuscitation cardiac and neurological function, in a porcine model of prolonged untreated cardiac arrest. METHODS: 18 female farm pigs, intubated and isoflurane anesthetized had 15 min of untreated ventricular fibrillation followed by standard CPR (SCPR). Nine animals were randomized to receive PC with four, controlled, 20-s pauses, during the first 3 min of CPR (SCPR + PC). Resuscitated animals had echocardiographic evaluation of their ejection fraction after 1 and 4 h and a blinded neurological assessment with a cerebral performance category (CPC) score assigned at 24 and 48 h. All animals received 12 h of post resuscitation mild therapeutic hypothermia. RESULTS: SCPR + PC animals had significant improvement in left ventricular ejection fraction at 1 and 4 h compared to SCPR (59 ± 11% vs 35 ± 7% and 55 ± 8% vs 31 ± 13% respectively, p < 0.01). Neurological function at 24 h significantly improved with SCPR + PC compared to SCPR alone (CPC: 2.7 ± 0.4 vs 3.8 ± 0.4 respectively, p = 0.003). Neurological function significantly improved in the SCPR + PC group at 48 h and the mean CPC score of that group decreased from 2.7 ± 0.4 to 1.7 ± 0.4 (p < 0.00001). CONCLUSIONS: Ischemic postconditioning with four 20-s pauses during the first 3 min of SCPR improved post resuscitation cardiac function and facilitated neurological recovery after 15 min of untreated cardiac arrest in pigs.