Head and thorax elevation during cardiopulmonary resuscitation using circulatory adjuncts is associated with improved survival.

BACKGROUND: 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. OBJECTIVES: To assess the probability of OHCA survival to hospital discharge after ACE-CPR versus C-CPR. METHODS: 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. RESULTS: 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 in <11 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. CONCLUSIONS: Compared with C-CPR controls, rapid initiation of ACE-CPR was associated with a higher likelihood of survival to hospital discharge after OHCA.

Magnitude of mitral valve closure plays a pivotal role in enhancing the forward blood flow during cardiac massage in dogs with ventricular fibrillation.

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.

Impact of head-up tilt on expiratory negative airway pressure ventilation-induced cardiovascular hemodynamics in the halothane-anesthetized intact microminipigs.

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.

Faster time to automated elevation of the head and thorax during cardiopulmonary resuscitation increases the probability of return of spontaneous circulation.

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). ROSCprobfor all rhythms was 34%(77/227). Median age (range) was 66 years (19-101) and 68% men. TheROSCprobfor 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).ROSCprobalso 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 and 12 min (n = 85),ROSCprobdeclined 5.6% for every minute elapsed (p = 0.024). For shockable rhythms, between 6 and 15 min (n = 23),ROSCprobdeclined 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.

Effects of mechanical ventilation with expiratory negative airway pressure on porcine pulmonary and systemic circulation: mechano-physiology and potential application.

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 < 40 mmHg in the animals assigned to ENAP treatment-group. Fluvoxamine induced cardiovascular collapse within 4 out of 5 animals. ENAP increased systolic pressure to > 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.

Saving the brain after mild-to-moderate traumatic injury: A report on new insights of the physiology underlying adequate maintenance of cerebral perfusion.

ABSTRACT: 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.

Effects of Cardiac Massage and ß-Blocker Pretreatment on the Success Rate of Cardiopulmonary Resuscitation Assessed by the Canine Ischemia/Reperfusion-Induced Ventricular Fibrillation Model.

BACKGROUND: Effects of rapid electrical defibrillation and ß-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 ß-blocker pretreatment may worsen hemodynamics and electrical stability after ROSC.

Improving post-cardiac arrest cerebral perfusion pressure by elevating the head and thorax.

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 ±â€¯SD. RESULTS: In Protocol A, intracranial pressure (ICP) (mmHg) was significantly lower post-ROSC with HUP (9.1 ±â€¯5.5) versus Flat (18.5 ±â€¯5.1) (p < 0.001). Conversely, CerPP was higher with HUP (62.5 ±â€¯19.9) versus Flat (53.2 ±â€¯19.1) (p = 0.004), respectively. Protocol A and B results comparing HUP versus Flat were similar. 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.

Rationale and Strategies for Development of an Optimal Bundle of Management for Cardiac Arrest.

OBJECTIVES: To construct a highly detailed yet practical, attainable roadmap for enhancing the likelihood of neurologically intact survival following sudden cardiac arrest. DESIGN SETTING AND PATIENTS: Population-based outcomes following out-of-hospital cardiac arrest were collated for 10 U.S. counties in Alaska, California, Florida, Ohio, Minnesota, Utah, and Washington. The 10 identified emergency medical services systems were those that had recently reported significant improvements in neurologically intact survival after introducing a more comprehensive approach involving citizens, hospitals, and evolving strategies for incorporating technology-based, highly choreographed care and training. Detailed inventories of in-common elements were collated from the ten 9-1-1 agencies and assimilated. For reference, combined averaged outcomes for out-of-hospital cardiac arrest occurring January 1, 2017, to February 28, 2018, were compared with concurrent U.S. outcomes reported by the well-established Cardiac Arrest Registry to Enhance Survival. INTERVENTIONS: Most commonly, interventions and components from the ten 9-1-1 systems consistently included extensive public cardiopulmonary resuscitation training, 9-1-1 system-connected smart phone applications, expedited dispatcher procedures, cardiopulmonary resuscitation quality monitoring, mechanical cardiopulmonary resuscitation, devices for enhancing negative intrathoracic pressure regulation, extracorporeal membrane oxygenation protocols, body temperature management procedures, rapid cardiac angiography, and intensive involvement of medical directors, operational and quality assurance officers, and training staff. MEASUREMENTS AND MAIN RESULTS: Compared with Cardiac Arrest Registry to Enhance Survival (n = 78,704), the cohorts from the 10 emergency medical services agencies examined (n = 2,911) demonstrated significantly increased likelihoods of return of spontaneous circulation (mean 37.4% vs 31.5%; p < 0.001) and neurologically favorable hospital discharge, particularly after witnessed collapses involving bystander cardiopulmonary resuscitation and shockable cardiac rhythms (mean 10.7% vs 8.4%; p < 0.001; and 41.6% vs 29.2%; p < 0.001, respectively). CONCLUSIONS: The likelihood of neurologically favorable survival following out-of-hospital cardiac arrest can improve substantially in communities that conscientiously and meticulously introduce a well-sequenced, highly choreographed, system-wide portfolio of both traditional and nonconventional approaches to training, technologies, and physiologic management. The commonalities found in the analyzed systems create a compelling case that other communities can also improve out-of-hospital cardiac arrest outcomes significantly by conscientiously exploring and adopting similar bundles of system organization and care.

Relationship between hemodynamic parameters and cerebral blood flow during cardiopulmonary resuscitation.

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.

Controlled progressive elevation rather than an optimal angle maximizes cerebral perfusion pressure during head up CPR in a swine model of cardiac arrest.

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 ±â€¯SD) were equivalent (44 ±â€¯22 and 47 ±â€¯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 ±â€¯17 versus 33 ±â€¯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.

Supraglottic airway devices variably develop negative intrathoracic pressures: A prospective cross-over study of cardiopulmonary resuscitation in human cadavers.

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.

Effect of controlled sequential elevation timing of the head and thorax during cardiopulmonary resuscitation on cerebral perfusion pressures in a porcine model of cardiac arrest.

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 ±â€¯SD. RESULTS: After 7 min of CPR, CerPPs were significantly higher in the 4-min vs 10-min CSE groups (53 ±â€¯14.4 vs 38.5 ±â€¯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 ±â€¯1.2 vs 6 ±â€¯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.

Intrathoracic pressure regulation therapy applied to ventilated patients for treatment of compromised cerebral perfusion from brain injury.

BACKGROUND: Reducing intrathoracic pressure in the setting of compromised cerebral perfusion due to acute brain injury has been associated with reduced intracranial pressure and enhanced cerebral perfusion pressure and blood flow in animals. Noninvasive active intrathoracic pressure regulation lowers intrathoracic pressure, increases preload, reduces the volume of venous blood and cerebral spinal fluid in the skull, and enhances cerebral blood flow. We examined the feasibility of active intrathoracic pressure regulation therapy in patients with brain injury. We hypothesized that active intrathoracic pressure regulation therapy would be associated with lowered intracranial pressure and increased cerebral perfusion pressure in these patients. METHODS: At three institutions, active intrathoracic pressure regulation therapy (CirQlator™, ZOLL) was utilized for 2 consecutive hours in five mechanically ventilated patients with brain injury. A 30-minute interval was used to collect baseline data and determine persistence of effects after device use. End-tidal carbon dioxide was controlled by respiratory rate changes during device use. The intracranial pressure, mean arterial pressure, and cerebral perfusion pressure were recorded at 5-minute intervals throughout all three periods of the protocol. Results for each interval are reported as mean and standard deviation. RESULTS: Intracranial pressure was decreased in all five patients by an average of 21% during (15 ± 4 mmHg) compared to before active intrathoracic pressure regulation (19 ± 4) (p = 0.005). This effect on intracranial pressure (15 ± 6) was still present in four of the five patients 30 minutes after therapy was discontinued (p = 0.89). As a result, cerebral perfusion pressure was 16% higher during (81 ± 10) compared to before active intrathoracic pressure regulation (70 ± 14) (p = 0.04) and this effect remained present 30 minutes after therapy was discontinued. No adverse events were reported. CONCLUSIONS: These data support the notion that active intrathoracic pressure regulation, in this limited evaluation, can successfully augment cerebral perfusion by lowering intracranial pressure and increasing mean arterial pressure in patients with mild brain injury. The measured effects were immediate on administration of the therapy and persisted to some degree after the therapy was terminated.

Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models.

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 ±â€¯6 for ACD + ITD SUP and 28.7 ±â€¯10 for ACD + ITD HUP (p = .007) in VF, -3.6 ±â€¯5 for ACD + ITD SUP and 7.8 ±â€¯9 for ACD + ITD HUP (p = .007) in PC, and 1.3 ±â€¯4 for ACD + ITD SUP and 11.3 ±â€¯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.