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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A multipronged approach to improve vital organ perfusion during cardiopulmonary resuscitation that includes sodium nitroprusside, active compression-decompression cardiopulmonary resuscitation, an impedance threshold device, and abdominal pressure (sodium nitroprusside-enhanced cardiopulmonary resuscitation) has been recently shown to increase coronary and cerebral perfusion pressures and higher rates of return of spontaneous circulation vs. standard cardiopulmonary resuscitation. To further reduce reperfusion injury during sodium nitroprusside-enhanced cardiopulmonary resuscitation, we investigated the addition of adenosine and four 20-sec controlled pauses spread throughout the first 3 mins of sodium nitroprusside-enhanced cardiopulmonary resuscitation. The primary study end point was 24-hr survival with favorable neurologic function after 15 mins of untreated ventricular fibrillation.Randomized, prospective, blinded animal investigation.Preclinical animal laboratory.Thirty-two female pigs (four groups of eight) 32±2 kg.After 15 mins of untreated ventricular fibrillation, isoflurane-anesthetized pigs received 5 mins of either standard cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine, or controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine. After 4 mins of cardiopulmonary resuscitation, all animals received epinephrine (0.5 mg) and a defibrillation shock 1 min later. Sodium nitroprusside-enhanced cardiopulmonary resuscitation-treated animals received sodium nitroprusside (2 mg) after 1 min of cardiopulmonary resuscitation and 1 mg after 3 mins of cardiopulmonary resuscitation. After 1 min of sodium nitroprusside-enhanced cardiopulmonary resuscitation, adenosine (24 mg) was administered in two groups.A veterinarian blinded to the treatment assigned a cerebral performance category score of 1-5 (normal, slightly disabled, severely disabled but conscious, vegetative state, or dead, respectively) 24 hrs after return of spontaneous circulation. Sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine, and controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine resulted in a significantly higher 24-hr survival rate compared to standard cardiopulmonary resuscitation (7 of 8, 8 of 8, and 8 of 8 vs. 2 of 8, respectively p.05). The mean cerebral performance category scores for standard cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine, or controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine were 4.6±0.7, 3±1.3, 2.5±0.9, and 1.5±0.9, respectively (p.01 for controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine compared to all other groups).Reducing reperfusion injury and maximizing circulation during cardiopulmonary resuscitation significantly improved functional neurologic recovery after 15 mins of untreated ventricular fibrillation. These results suggest that brain resuscitation after prolonged cardiac arrest is possible with novel, noninvasive approaches focused on reversing the mechanisms of tissue injury.

Background Electromagnetic interference (EMI) induced by electrocautery during surgery in patients with cardiac pacemakers or implanted cardioverter-defibrillators (ICDs) may inhibit pacing and cause inappropriate tachyarrhythmia oversensing. In particular, susceptibility to EMI may be enhanced in ICDs by frequently used wide interelectrode sensing (i.e., integrated bipolar sensing). Consequently, ICD function is usually disabled preoperatively and restored later by noninvasive programming. Because sensing by closely spaced electrodes (i.e., true bipolar) may be less susceptible to EMI, preoperative programming to a true bipolar mode may minimize the need for perioperative programming while preserving device function. Methods Our study population consisted of 23 consecutive patients either receiving a new ICD or undergoing ICD pulse generator change. In each patient, electrocautery-induced EMI was initiated with the ICD in the closely spaced sensing configuration and again during widely spaced sensing. Results In comparing the 2 sensing modes, right ventricular electrogram amplitude was significantly greater and EMI noise amplitude tended to be greater with widely spaced bipolar sensing. Furthermore, widely spaced bipolar sensing was associated with ICD pacing inhibition in 22 of 23 patients and incorrect "ventricular fibrillation" detection in 17 of 23 patients. Conversely, closely spaced bipolar sensing was not accompanied by either pacing inhibition or incorrect ventricular fibrillation sensing. Conclusion Closely spaced bipolar sensing (i.e., true bipolar) appropriately rejects electrocautery-induced EMI. Programming implanted devices to closely spaced bipolar sensing may minimize the need for perioperative reprogramming while preserving intraoperative device operation.

In 2003, the International Liaison Committee on Resuscitation published a consensus document on education in resuscitation that strongly recommended that “…instruction in CPR [cardiopulmonary resuscitation] be incorporated as a standard part of the school curriculum.”1 The next year the American Heart Association (AHA) recommended that schools “…establish a goal to train every teacher in CPR and first aid and train all students in CPR” as part of their preparation for a response to medical emergencies on campus.2 Since that time, there has been an increased interest in legislation that would mandate that school curricula include training in CPR or CPR and automated external defibrillation. Laws or curriculum content standards in 36 states (as of the 2009–2010 school year) now encourage the inclusion of CPR training programs in school curricula. The language in those laws and standards varies greatly, ranging from a suggestion that students “recognize” the steps of CPR to a requirement for certification in CPR. Not surprisingly, then, implementation is not uniform among states, even those whose laws or standards encourage CPR training in schools in the strongest language. This statement recommends that training in CPR and familiarization with automated external defibrillators (AEDs) should be required elements of secondary school curricula and provides the rationale for implementation of CPR training, as well as guidance in overcoming barriers to implementation. Sudden cardiac arrest is a leading cause of death in the United States and Canada. It is estimated that each year emergency medical services (EMS) personnel assess 294 851 (quasi-confidence intervals, 236 063 to 325 007) out-of-hospital cardiac arrests (OHCAs) in the United States. Survival, which is defined as being discharged alive from the hospital, varies widely by region (3.0% to 16.3%; median, 8.4%), but the overall average rate of survival to discharge from the hospital is estimated …

Active compression-decompression cardiopulmonary resuscitation (CPR) with decreased intrathoracic pressure in the decompression phase can lead to improved haemodynamics compared with standard CPR. We aimed to assess effectiveness and safety of this intervention on survival with favourable neurological function after out-of-hospital cardiac arrest.In our randomised trial of 46 emergency medical service agencies (serving 2·3 million people) in urban, suburban, and rural areas of the USA, we assessed outcomes for patients with out-of-hospital cardiac arrest according to Utstein guidelines. We provisionally enrolled patients to receive standard CPR or active compression-decompression CPR with augmented negative intrathoracic pressure (via an impedance-threshold device) with a computer-generated block randomisation weekly schedule in a one-to-one ratio. Adults (presumed age or age ≥18 years) who had a non-traumatic arrest of presumed cardiac cause and met initial and final selection criteria received designated CPR and were included in the final analyses. The primary endpoint was survival to hospital discharge with favourable neurological function (modified Rankin scale score of ≤3). All investigators apart from initial rescuers were masked to treatment group assignment. This trial is registered with ClinicalTrials.gov, number NCT00189423.2470 provisionally enrolled patients were randomly allocated to treatment groups. 813 (68%) of 1201 patients assigned to the standard CPR group (controls) and 840 (66%) of 1269 assigned to intervention CPR received designated CPR and were included in the final analyses. 47 (6%) of 813 controls survived to hospital discharge with favourable neurological function compared with 75 (9%) of 840 patients in the intervention group (odds ratio 1·58, 95% CI 1·07-2·36; p=0·019]. 74 (9%) of 840 patients survived to 1 year in the intervention group compared with 48 (6%) of 813 controls (p=0·03), with equivalent cognitive skills, disability ratings, and emotional-psychological statuses in both groups. The overall major adverse event rate did not differ between groups, but more patients had pulmonary oedema in the intervention group (94 [11%] of 840) than did controls (62 [7%] of 813; p=0·015).On the basis of our findings showing increased effectiveness and generalisability of the study intervention, active compression-decompression CPR with augmentation of negative intrathoracic pressure should be considered as an alternative to standard CPR to increase long-term survival after cardiac arrest.US National Institutes of Health grant R44-HL065851-03, Advanced Circulatory Systems.

Out-of-hospital cardiac arrest continues to be an important public health problem, with large and important regional variations in outcomes. Survival rates vary widely among patients treated with out-of-hospital cardiac arrest by emergency medical services and among patients transported to the hospital after return of spontaneous circulation. Most regions lack a well-coordinated approach to post–cardiac arrest care. Effective hospital-based interventions for out-of-hospital cardiac arrest exist but are used infrequently. Barriers to implementation of these interventions include lack of knowledge, experience, personnel, resources, and infrastructure. A well-defined relationship between an increased volume of patients or procedures and better outcomes among individual providers and hospitals has been observed for several other clinical disorders. Regional systems of care have improved provider experience and patient outcomes for those with ST-elevation myocardial infarction and life-threatening traumatic injury. This statement describes the rationale for regional systems of care for patients resuscitated from cardiac arrest and the preliminary recommended elements of such systems. Many more people could potentially survive out-of-hospital cardiac arrest if regional systems of cardiac resuscitation were established. A national process is necessary to develop and implement evidence-based guidelines for such systems that must include standards for the categorization, verification, and designation of components of such systems. The time to do so is now.

Objective: The purpose of this study is to: 1) describe a newly discovered mechanism of blood flow to the brain during cardiopulmonary resuscitation using the impedance threshold device in a piglet model of cardiac arrest, and 2) describe the survival benefits in humans of applying all of the highly recommended changes in the 2005 guidelines related to increasing circulation during cardiopulmonary resuscitation, including use of the impedance threshold device, from six emergency medical services systems in the United States. Design: Animal studies prospective trial with each piglet serving as its own control. Historical controls were used for the human studies. Subjects: Piglets and patients with out-of-hospital cardiac arrest. Interventions: Piglets (10-12 kg) were treated with an active (n = 9) or sham (n = 9) impedance threshold device after 6 mins of ventricular fibrillation. Humans were treated with cardiopulmonary resuscitation per the American Heart Association 2005 guidelines and the impedance threshold device. Measurements and Main Results: Animals: The primary endpoint in the piglet study was carotid blood flow which increased from 59 mL/min without an impedance threshold device to 91 mL/min (p = 0.017) with impedance threshold device use. Airway pressures during the chest recoil phase decreased from -0.46 mm Hg to -2.59 mm Hg (p = 0.0006) with the active impedance threshold device. Intracranial pressure decreased more rapidly and to a greater degree during the decompression phase of cardiopulmonary resuscitation with the active impedance threshold device. Humans: Conglomerate quality assurance data were analyzed from six emergency medical services systems in the United States serving a population of 3 million people. There were 920 patients treated for cardiac arrest after implementation of the 2005 American Heart Association guidelines, including impedance threshold device use, and 1750 patients in the control group during the year before implementation. Demographics were similar between the two groups. Survival to hospital discharge was 9.3% in the control group versus 13.6% in the intervention group. The odds ratio, 95% confidence interval, and p value were 1.54 (1.19-1.99) and p = 0.0008, respectively. This survival advantage was conferred to patients with a presenting cardiac arrest rhythm of ventricular fibrillation (28.5% vs. 18.0%, p = 0.0008). Conclusions: Use of the impedance threshold device in piglets increased carotid blood flow and coronary and cerebral perfusion pressures and reduced intracranial pressure during the decompression phase of cardiopulmonary resuscitation at a faster rate than controls, resulting in a longer duration of time when intracranial pressures are at their nadir. Patients in six emergency medical services systems treated with the impedance threshold device together with the renewed emphasis on more compressions, fewer ventilations, and complete chest wall recoil had a nearly 50% increase in survival rates after out-of-hospital cardiac arrest compared with historical controls.

INTRODUCTION Symptoms of orthostatic intolerance, e.g., following prolonged bed rest and microgravity exposure, are associated with reductions in cerebral blood flow. We tested the hypothesis that spontaneously breathing through an impedance threshold device (ITD) would attenuate the fall in cerebral blood flow velocity (CBFV) during a hypotensive orthostatic challenge and reduce the severity of reported symptoms. METHODS While breathing through either an active ITD (-7 cm H2O inspiratory impedance) or a sham ITD (no impedance), 19 subjects performed a squat stand test (SST). Symptoms upon stand were recorded on a 5-point scale (1 = normal; 5 = faint) of subject-perceived rating (SPR). To address our hypothesis, only data from symptomatic subjects (SPR > 1 during the sham trial) were analyzed (N = 9). Mean arterial blood pressure (MAP) and mean CBFV were measured continuously throughout the SST and analyzed in time and frequency domains. RESULTS Breathing with the active ITD during the SST reduced the severity of orthostatic symptoms in eight of the nine symptomatic subjects (sham ITD SPR, 1.9 +/- 0.1; active ITD SPR, 1.1 +/- 0.1), but there was no statistically distinguishable difference in the reduction of mean CBFV between the two trials (sham ITD, -39 +/- 3% vs. active ITD, -44 +/- 3%). High frequency oscillations in mean CBFV, however, were greater during the active ITD trial (7.8 +/- 2.6 cm x s(-2)) compared with the sham ITD trial (2.5 +/- 0.9 cm x s(-2)). CONCLUSIONS Higher oscillations in CBFV while breathing with the active ITD may account for the reduction in symptom severity during orthostatic hypotension despite the same fall in absolute CBFV.

ObjectivesWe sought to identify the impact of cardiac resynchronization therapy (CRT) on atrial tachyarrhythmia (AT) susceptibility in patients with left ventricular (LV) systolic dysfunction in whom worsening heart failure (HF) resulted in upgrade from conventional dual-chamber pulse generator to cardiac resynchronization therapy-defibrillator (CRT-D).BackgroundCardiac resynchronization therapy with a defibrillator improves survival rates and symptoms in patients with LV systolic dysfunction but little is known about its effects on AT incidence in the same patient population.MethodsTwenty-eight consecutive HF patients who underwent device upgrade to CRT-D were included. Patients had ≥2 device interrogations in the 1 year before upgrade and ≥3 interrogations in the 18- to 24-month follow-up after upgrade. Echocardiographic parameters were assessed before and at 3 to 6 months after CRT-D. Additional observations included number of hospital stays, HF clinical status, and concomitant pharmacological therapy. By virtue of this study design, each patient served as his/her own control. Statistical analysis was performed by 2-tailed paired ttest and with nonparametric tests where appropriate.ResultsWithin 3 months after CRT, the number of HF patients with documented AT decreased significantly from the immediate pre-CRT value and tended to decline with time. At 1-year follow-up, 90% of patients were AT-free compared with 14% of patients 3 months before CRT (p < 0.001). Furthermore, the number of AT episodes/year and their maximum duration decreased after CRT (mean ± SD; 181 ± 50 vs. 50 ± 20.2, p < 0.05, and 220.8 ± 87 s vs. 28 ± 21 s, p < 0.05, respectively). Finally, CRT was associated with improved LV ejection fraction (mean ± SD; from 26 ± 5.3% to 31 ± 7%, p < 0.001) and reduced number of HF or arrhythmia hospital stays (p < 0.05).ConclusionsOur findings support the view that CRT might decrease AT susceptibility in HF patients with LV systolic dysfunction.

Implantable cardioverter defibrillators (ICD) reduce arrhythmic mortality in a wide range of patients with poor left ventricular (LV) function. However, whether ICD therapy is equally effective in younger and older patients remains uncertain. To address this question, we compared ICD-documented ventricular tachyarrhythmia burden in patients75 years of age (Group 1) andor= 75 years of age (Group 2).Data were obtained from 208 consecutive ICD-treated patients: 159 Group 1 (mean age 59 +/- 12), and 49 Group 2 (mean age 79 +/- 3). Demographic and clinical features including presenting arrhythmias, LV ejection fraction, and nature of heart disease were similar. Medications were comparable except that amiodarone use was more frequent in Group 2.The numbers of combined ventricular tachycardia (VT) and ventricular fibrillation (VF) episodes per month were 0.4 +/- 2 and 0.3 +/- 2 for groups 1 and 2, respectively (P = 0.7). Individually, VT episodes per month were 0.4 +/- 2 and 0.3 +/- 2 (P = 0.7) and VF episodes per month were 0.003 +/- 0.01 and 0.03 +/- 0.2 (P = 0.2) for the two groups, respectively. The mean duration and average cycle length of arrhythmias were 3.1 +/- 20.4 s and 275 +/- 119 ms in Group 1, and 6 +/- 45 s and 285 +/- 114 ms in Group 2 (P values, 0.6 and 0.8). The mean time between the ICD implantation and the first episode of a device-treated arrhythmia was comparable in the two groups. Thirty-six patients died during follow-up; 22 (14%) Group 1 and 14 (29%) Group 2 (P = 0.02), almost exclusively on a non-sudden cardiac basis. Thus, despite higher ultimate mortality in older patients, both the nature and characteristics of spontaneous arrhythmia recurrence, and the time to first apparently beneficial therapy, were similar during follow-up in the two groups.In terms of reversing potentially life-threatening arrhythmias, the rationale for ICD therapy is comparable in older and younger individuals.

Outcomes after cardiac arrest remain poor more than a half a century after closed chest cardiopulmonary resuscitation (CPR) was first described. This review article is focused on recent insights into the physiology of blood flow to the heart and brain during CPR. Over the past 20 years, a greater understanding of heart-brain-lung interactions has resulted in novel resuscitation methods and technologies that significantly improve outcomes from cardiac arrest. This article highlights the importance of attention to CPR quality, recent approaches to regulate intrathoracic pressure to improve cerebral and systemic perfusion, and ongoing research related to the ways to mitigate reperfusion injury during CPR. Taken together, these new approaches in adult and pediatric patients provide an innovative, physiologically based road map to increase survival and quality of life after cardiac arrest.

Background: Chest compressions during conventional cardiopulmonary resuscitation (C-CPR) increase arterial and venous pressures simultaneously, delivering bidirectional high pressure compression waves to the brain. It is possible that this may be detrimental neurologically and could be partially overcome by elevating the head during CPR. Previous animal study work using a tilt table has shown that a 30° head up position for the entire body during CPR significantly increases cerebral blood flow and cerebral perfusion pressure (CerPP) over a period of 5 minutes. We hypothesize that elevating the head and shoulders only will increase CerPP over a prolonged period of time with two different CPR techniques. Methods: Female farm pigs were sedated, intubated, anesthetized, and placed on a table designed to elevate the head and shoulders to 30°. After 8 min of untreated ventricular fibrillation and 2 min of automated C-CPR in the supine position, pigs were randomized to head up (HUP) or supine (SUP) CPR for 20 more min. In Group A, pigs were treated after 2 min of C-CPR with automated active compression decompression (ACD) CPR at 100 cycles/min plus an impedance threshold device (ITD), randomized to HUP (n=8) or SUP (n=8). In Group B, pigs were randomized after 2 min of C-CPR to treatment with HUP (n=7) or SUP (n=7) automated C-CPR. After 22 total min of CPR, defibrillation was performed. The primary outcome of the study was the comparison of CerPP at 22 min between HUP and SUP positions within each group. Results: After 22 min of CPR, CerPP (mmHg) was 39±7 with HUP versus 14±4 with SUP CPR (p=0.013) in Group A and 3.4±2.2 with HUP versus -6.3±2.6 with SUP CPR (p = 0.014) in Group B. There was no significant difference within groups for coronary perfusion pressure (CPP) after 22 min, but CPP trended higher with HUP in Group A (32.0 ± 4.9) versus SUP (18.8 ± 4.7)(p=0.072). The CPPs in Group B were 5.8 ± 1.1 with HUP versus 3.3±1.8 with SUP CPR, p=0.26). In Group A, 6/8 pigs were resuscitated in both positions where no pigs could be resuscitated in Group B. Conclusions: The HUP position using two different CPR techniques significantly improved CerPP over a prolonged period of time. This simple maneuver has the potential to improve neurological outcomes after cardiac arrest.

Ischemic postconditioning (IPC) during cardiopulmonary resuscitation (CPR) increases neurologically intact survival in a porcine cardiac arrest model. We investigated the effect of IPC on mitochondrial respiration, an important therapeutic target for resuscitation, during CPR in this model. Blood pressure and ECG were continuously recorded. After 15 min of ventricular fibrillation, animals received standard CPR +/- IPC. IPC consisted of 3 cycles of 20 sec compression / 20 sec pause for the first 2 min of CPR. Cardiac mitochondria were isolated after 4 min. Closed-cell respiration was measured for complex I (pyruvate+malate) and II (succinate+rotenone). In IPC-treated animals vs. standard CPR, complex I and II respiratory control indices (RCI), calculated as the ratio of state 3:4 respiration, were higher (6.7±0.8 and 3.1±0.6 vs. 4.3±0.7 and 2.4±0.2, respectively) and complex I and II state 4 respiration (µmol O2*hr-1*mg-1) were lower (1.7±0.2 and 2.7±0.3 vs. 2.3±0.5 and 3.3±0.5, respectively). Blood press...

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15min of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17min of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) ( n =8) or Bundle therapy with stutter ACD CPR+ITD+sevoflurane+P188 ( n =12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48h), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48h). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17min of untreated cardiac arrest in pigs. All studies were performed with approval from the Institutional Animal Care Committee of the Minneapolis Medical Research Foundation (protocol #12-11).

Objective: The purpose of this study is to review cardiopulmonary resuscitation hemodynamics and vital organ blood flow in animal models with the use of the impedance threshold device (ITD) and to correlate these findings with the results of human clinical trials. Results: Animal studies have demonstrated near normalization of cerebral blood flow and an increase between 50% and 100% in cardiac blood flow with use of the ITD. Coincident coronary perfusion pressure is significantly increased with the ITD. Results of human clinical trials generally reflect the data seen in animal models, with near normal blood pressure during active compression-decompression cardiopulmonary resuscitation and the ITD, near doubling of blood pressure with standard cardiopulmonary resuscitation plus the ITD, and significantly increased short-term survival rates. Conclusions: Improved vital organ perfusion with ITD use during cardiopulmonary resuscitation is an important advance in resuscitation. Incorporation of the ITD into protocols that improve other aspects of the care of patients during cardiac arrest and after successful resuscitation should result in further benefit from the ITD. (Crit Care Med 2006; 34[Suppl.]:S466-S473)

The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have recently published, in both the Journal of the American College of Cardiology (JACC) and Circulation, a Scientific Statement on the Evaluation of Syncope ('Statement'). This Scientific Statement was commissioned to provide guidance for clinicians regarding the evaluation of patients who present with 'syncope'. The Statement was not intended to be a formal set of practice guidelines. However, in the absence of generally accepted practice guidelines in North America, the Statement's potential impact on clinical care may be more far-reaching than expected; it may erroneously be considered to be the authoritative 'de-facto' guideline document. This commentary, submitted by a multidisciplinary consortium of more than 60 physicians with expertise in the management of transient loss of consciousness (TLOC), points out that in many respects the ACCF/AHA Syncope Statement fails to address long-standing clinical errors associated with the evaluation of episodes of apparent TLOC, including syncope. If not appropriately revised, the current Statement may lead to both inadequate patient care as well as a potentially damaging legal environment for physicians undertaking evaluation of patients who present with transient loss of consciousness.

ObjectivesA rapid, ice-cold saline flush combined with active compression-decompression (ACD) plus an inspiratory impedance threshold device (ITD) cardiopulmonary resusitation (CPR) will cool brain tissue more effectively than with standard CPR (S-CPR) during cardiac arrest (CA).BackgroundEarly institution of hypothermia after CPR and return of spontaneous circulation improves survival and outcomes after CA in humans.MethodsVentricular fibrillation (VF) was induced for 8 min in anesthetized and tracheally intubated pigs. Pigs were randomized to receive either ACD + ITD CPR (n = 8) or S-CPR (n = 8). After 2 min of CPR, 30 ml/kg ice-cold saline (3°C) was infused over the next 3 min of CPR via femoral vein followed by up to three defibrillation attempts (150 J, biphasic). If VF persisted, epinephrine (40 μg/kg) and vasopressin (0.3 U/kg) were administered followed by three additional defibrillation attempts. Hemodynamic variables and temperatures were continuously recorded.ResultsAll ACD + ITD CPR pigs (8 of 8) survived (defined as 15 min of return of spontaneous circulation [ROSC]) versus 3 of 8 pigs with S-CPR (p < 0.05). In survivors, brain temperature (°C) measured at 2-cm depth in brain cortex 1 min after ROSC decreased from 37.6 ± 0.2 to 35.8 ± 0.3 in ACD + ITD CPR versus 37.8 ± 0.2 to 37.3 ± 0.3 in S-CPR (p < 0.005). Immediately before defibrillation: 1) right atrial systolic/diastolic pressures (mm Hg) were lower (85 ± 19, 4 ± 1) in ACD + ITD CPR than S-CPR pigs (141 ± 12, 8 ± 3, p < 0.01); and 2) coronary perfusion pressures (mm Hg) were higher in ACD + ITD CPR (28.3 ± 2) than S-CPR pigs (17.4 ± 3, p < 0.01).ConclusionsA rapid ice-cold saline infusion combined with ACD + ITD CPR during cardiac arrest induces cerebral hypothermia more rapidly immediately after ROSC than with S-CPR.

Implantable cardioverter defibrillators have been shown to provide similar survival benefits for patients who have left ventricular dysfunction due to ischemic heart disease and for subsets of patients who have nonischemic cardiomyopathy. Findings in this study extend these observations by showing that patients who have ischemic or nonischemic heart disease and receive implantable cardioverter defibrillators not only have comparable mortality rates but also similar tachyarrhythmia frequencies during follow-up; further, mortality and tachyarrhythmia outcomes are independent of initial arrhythmia indication.

Lay rescuer automated external defibrillator (AED) programs may increase the number of people experiencing sudden cardiac arrest who receive bystander cardiopulmonary resuscitation (CPR), can reduce time to defibrillation, and may improve survival from sudden cardiac arrest. These programs require an organized and practiced response, with rescuers trained and equipped to recognize emergencies, activate the emergency medical services system, provide CPR, and provide defibrillation. To determine the effect of public access defibrillation (PAD) programs on survival and other outcomes after SCA, the National Heart, Lung, and Blood Institute, the American Heart Association (AHA), and others funded a large prospective randomized trial. The results of this study were recently published in The New England Journal of Medicine and support current AHA recommendations for lay rescuer AED programs and emphasis on planning, training, and practice of CPR and use of AEDs. The purpose of this statement is to highlight important findings of the Public Access Defibrillation Trial and summarize implications of these findings for healthcare providers, healthcare policy advocates, and the AHA training network.

Introduction: Biventricular cardiac pacemakers provide important hemodynamic benefit in selected patients with heart failure and severe left ventricular (LV) dysfunction. Nevertheless, these patients remain at high mortality risk. To address this issue, we examined mortality outcome in patients with heart failure treated with biventricular pacemakers alone and those treated with biventricular implantable cardioverter defibrillators (ICDs). Methods and Results: The study population consisted of 126 consecutive patients with LV dysfunction and heart failure who received either a biventricular ICD (n = 62) or a biventricular pacemaker (n = 64) between January 1998 and December 2002. A minimum 12 months of follow-up was obtained in all survivors. ICD indications were conventional in all patients. Kaplan-Meier actuarial method and log rank statistics were used to calculate and compare survival rates in both groups. Comparison of mortality rates utilized Chi-square test. The two groups had similar clinical and demographic features, LV ejection fraction, and medication use. Average follow-up times were 13 ± 11.8 months (range 4–60) and 18 ± 13.2 months (range 0.5–53) for biventricular ICD and pacemaker groups, respectively. Overall mortality rate was significantly lower in the biventricular ICD group (13%, 8 deaths) compared to the pacemaker group (41%, 26 deaths) (P = 0.01). Further, the predominant survival benefit for ICD-treated patients becomes evident after the first 12 months of follow-up. Conclusion: The findings in this study, although necessarily limited in their interpretation by the absence of treatment randomization, suggest that biventricular ICDs offer a survival benefit compared to biventricular pacing alone. Furthermore, this benefit may be most apparent if other clinical factors do not preclude patient survival >1 year postimplant.

Background:The basic premise that frequent ventilations during cardiopulmonary resuscitation (CPR) are a necessity for tissue oxygenation has recently been challenged. An inspiratory impedance threshold device (ITD) recently has also been shown to increase CPR efficiency, principally by augmenting circulation with little impact on ventilation. The optimal compression to ventilation (C/V) is not known for this new device. The purpose of this study was to compare the currently recommended C/V ratio of 5:1 with a 10:1 ratio, ± the ITD, to optimize circulation and oxygenation during CPR. Methods: Thirty-two adult pigs weighing 26–31 kg were randomized to CPR with varying C/V ratios ± the ITD as follows: A = 5:1, B = 5:1 + ITD, C = 10:1, D = 10:1 + ITD. After 6 min of untreated ventricular fibrillation (VF), closed-chest standard CPR was performed with an automatic piston device that does not impede passive chest wall recoil, at a continuous compression rate of 100 min −1 . Synchronous breaths were given every 5 or 10 compressions during the decompression phase depending on the group. CPR was performed for 6 min and physiological variables were measured throughout the experimental protocol. Results: A reduction in the frequency of ventilation from 5:1 to 10:1 resulted in significantly improved arterial and coronary perfusion pressure in a pig model of cardiac arrest. Addition of an ITD resulted in further increases in arterial and coronary perfusion pressures with both 5:1 and 10:1 C/V ratios, without compromising oxygenation. Conclusion: CPR efficiency can be optimized by changing the compression: ventilation ratio from 5:1 to 10:1 and with concurrent use of the inspiratory threshold device. © 2004 Published by Elsevier Ireland Ltd.

Background— Active compression-decompression (ACD) CPR combined with an inspiratory impedance threshold device (ITD) improves vital organ blood flow during cardiac arrest. This study compared survival rates with ACD+ITD CPR versus standard manual CPR (S-CPR). Methods and Results— A prospective, controlled trial was performed in Mainz, Germany, in which a 2-tiered emergency response included early defibrillation. Patients with out-of-hospital arrest of presumed cardiac pathogenesis were sequentially randomized to ACD+ITD CPR or S-CPR by the advanced life support team after intubation. Rescuers learned which method of CPR to use at the start of each work shift. The primary end point was 1-hour survival after a witnessed arrest. With ACD+ITD CPR (n=103), return of spontaneous circulation and 1- and 24-hour survival rates were 55%, 51%, and 37% versus 37%, 32%, and 22% with S-CPR (n=107) ( P =0.016, 0.006, and 0.033, respectively). One- and 24-hour survival rates in witnessed arrests were 55% and 41% with ACD+ITD CPR versus 33% and 23% in control subjects ( P =0.011 and 0.019), respectively. One- and 24-hour survival rates in patients with a witnessed arrest in ventricular fibrillation were 68% and 58% after ACD+ITD CPR versus 27% and 23% after S-CPR ( P =0.002 and 0.009), respectively. Patients randomized ≥10 minutes after the call for help to the ACD+ITD CPR had a 3 times higher 1-hour survival rate than control subjects ( P =0.002). Hospital discharge rates were 18% after ACD+ITD CPR versus 13% in control subjects ( P =0.41). In witnessed arrests, overall neurological function trended higher with ACD+ITD CPR versus control subjects ( P =0.07). Conclusions— Compared with S-CPR, ACD+ITD CPR significantly improved short-term survival rates for patients with out-of-hospital cardiac arrest. Additional studies are needed to evaluate potential long-term benefits of ACD+ITD CPR.

The implantable loop recorder (ILR) has become an important tool for evaluating patients with recurrent syncope. Second generation ILRs have the ability to record events either automatically (auto activated) or by manual activation (patient activated). In an attempt to evaluate the relative utility of the auto-activation feature, this study stratified ILR events based on a grading system designed to classify detected arrhythmias in terms of the likelihood that they provide a diagnostic basis for syncope. Data from 50 patients (27 men, mean age 64 +/- 22 years) who underwent ILR implantation for investigation of recurrent syncope were assessed. The arrhythmia syncope grading system used 5 levels, ranging from grade 0 (rhythm recorded during syncope) to grade IV (rhythm unlikely to provide a diagnostic basis for syncope). Thirty-six patients (72%) demonstratedor =1 auto-activated or patient-activated recording during a follow-up of 14.3 +/- 7.9 months. Of the total of 529 recordings, 223 (194 after auto activation [86.9%]) from 30 patients showed a rhythm abnormality. Auto activation was more effective for documenting arrhythmias that were recorded during syncope or those with highest probability of providing a syncope diagnosis (grade 0 or I arrhythmias: auto activated, 19 patients, patient activated, 3 patients). Times from ILR implantation to first grade 0 and grade I arrhythmias were 13.4 and 7.8 months, respectively. The ILR auto-activation feature proved effective in providing a high probability basis for syncope (196 arrhythmia recordings [87.1%] in 27 patients) and enhanced the diagnostic effectiveness of the device compared with patient activation alone (29 arrhythmia recordings [12.9%] in 6 patients).

UNLABELLED: During normothermic cardiac arrest, a combination of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) with the inspiratory threshold valve (ITV) significantly improves vital organ blood flow, but this technique has not been studied during hypothermic cardiac arrest. Accordingly, we evaluated the hemodynamic effects of ACD + ITV CPR before, and after, the administration of vasopressin in a porcine model of hypothermic cardiac arrest. Pigs were surface-cooled until their body core temperature was 26 degrees C. After 10 min of untreated ventricular fibrillation, 14 animals were randomly assigned to either ACD CPR with the ITV (n = 7) or to standard (STD) CPR (n = 7). After 8 min of CPR, all animals received 0.4 U/kg vasopressin IV, and CPR was maintained for an additional 10 min in each group; defibrillation was attempted after 28 min of cardiac arrest, including 18 min of CPR. Before the administration of vasopressin, mean +/- SEM common carotid blood flow was significantly higher in the ACD + ITV group compared with STD CPR (67 +/- 13 versus 26 +/- 5 mL/min, respectively; P < 0.025). After vasopressin was given at minute 8 during CPR, mean +/- SEM coronary perfusion pressure was significantly higher in the ACD + ITV group, but did not increase in the STD group (29 +/- 3 versus 15 +/- 2 mm Hg, and 25 +/- 1 versus 14 +/- 1 mm Hg at minute 12 and 18, respectively; P < 0.001); mean +/- SEM common carotid blood flow remained higher at respective time points (33 +/- 8 versus 10 +/- 3 mL/min, and 31 +/- 7 versus 7 +/- 3 mL/min, respectively; P < 0.01). Without active rewarming, spontaneous circulation was restored and maintained for 1 h in three of seven animals in the ACD + ITV group versus none of seven animals in the STD CPR group (not significant). During hypothermic cardiac arrest, ACD CPR with the ITV improved common carotid blood flow compared with STD CPR alone. Moreover, after the administration of vasopressin, coronary perfusion pressure was significantly higher during ACD + ITV CPR, but not during STD CPR. IMPLICATIONS: New strategies are needed to improve the efficiency of cardiopulmonary resuscitation (CPR) in hypothermic cardiac arrest. Active compression-decompression CPR with the inspiratory threshold valve improved carotid blood flow (and coronary perfusion pressure with vasopressin) compared with standard CPR.

OBJECTIVE We recently demonstrated that vasopressin alone resulted in a poorer outcome in a pediatric porcine model of asphyxial cardiac arrest when compared with epinephrine alone or with epinephrine plus vasopressin in combination. Accordingly, this study was designed to differentiate whether the inferior effects of vasopressin in pediatrics were caused by the type of cardiac arrest. DESIGN Prospective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SETTING University hospital laboratory. SUBJECTS Eighteen piglets weighing 8-11 kg. INTERVENTIONS After 8 mins of ventricular fibrillation and 8 mins of cardiopulmonary resuscitation, either 0.4 units/kg vasopressin (n = 6), 45 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered. Six minutes after drug administration, a second respective bolus dose of 0.8 units/kg vasopressin, 200 microg/kg epinephrine, or a combination of 200 microg/kg epinephrine with 0.8 units/kg vasopressin was given. Defibrillation was attempted 20 mins after initiating cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS Mean +/- sem left ventricular myocardial blood flow 2 mins after each respective drug administration was 65 +/- 4 and 70 +/- 13 mL x min(-1) x 100 g(-1) in the vasopressin group; 83 +/- 42 and 85 +/- 41 mL x min(-1) x 100 g(-1) in the epinephrine group; and 176 +/- 32 and 187 +/- 29 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p

Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) with the inspiratory threshold valve (ITV) has been recently recommended by the American Heart Association for treatment of adults in cardiac arrest (class IIb: alternative, useful intervention), but this new technique has never been used in a pediatric population. Thus, this study was designed to evaluate ACD + ITV CPR in a young porcine model of cardiac arrest. After 10 min of ventricular fibrillation, and 8 min of standard CPR, ACD + ITV CPR was performed in seven 4- to 6-wk-old pigs (8-12 kg); defibrillation was attempted 8 min later. Within 2 min after initiation of ACD + ITV CPR, mean (+/- SEM) coronary perfusion pressure increased from 18 +/- 2 to 24 +/- 3 mm Hg (p = 0.018). During standard versus ACD + ITV CPR, mean left ventricular myocardial and total cerebral blood flow was 59 +/- 21 versus 126 +/- 32 mL.min(-1).100 g(-1), and 36 +/- 7 versus 60 +/- 15 mL.min(-1).100 g(-1), respectively (p = 0.028). Six of seven animals were successfully defibrillated, and survived15 min. In conclusion, the combination of ACD + ITV CPR significantly increased both coronary perfusion pressure and vital organ blood flow after prolonged standard CPR in this young porcine model of ventricular fibrillation.

Despite aggressive measures for the treatment of cardiovascular collapse and cardiac arrest, the hypotension associated with these malignant processes usually leads to profound vital-organ ischemia and death. A fundamental therapeutic challenge of such life-threatening processes is the restoration of adequate blood flow to the heart and the brain. However, to maintain adequate forward blood flow out of the heart, venous blood return must be drawn back into the heart. With the exception of administration of exogenous fluid replacement, there are limited ways to enhance blood flow back to the heart during prolonged hypotension. This article describes the potential value of a new impedance threshold valve for the treatment of cardiac arrest and hypotension. The valve was designed to create a vacuum within the thorax during the decompression phase of cardiopulmonary resuscitation or during inhalation. By transiently blocking inspiratory gas exchange during the decompression phase of cardiopulmonary resuscitation, after phrenic nerve-stimulated gasping, or during spontaneous ventilation, the impedance-valve concept may have clinical value in the treatment of patients in cardiac arrest, hemorrhagic shock, and cardiovascular collapse secondary to a number of life-threatening clinical processes.

Objectives Emergency medical research performed under federal regulation 21 § CFR 50.24 provides a means to protect human subjects and investigate novel time-sensitive treatments. Although prospective individual consent is not required for studies conducted under this regulation, consent from a legally authorized representative (LAR) or the patient at the earliest feasible opportunity is required to obtain short- and long-term outcome data. The objective of this study was to determine which demographic, cardiac arrest, and patient outcome characteristics predicted the likelihood of obtaining informed consent following enrollment under exception from informed consent in a multicenter cardiac arrest study. Methods This investigation was an analysis of data collected during a multisite, randomized, controlled, out-of-hospital cardiac arrest clinical trial performed under 21 § CFR 50.24. Research personnel attempted to obtain informed consent from LARs and subjects for medical records review of primary outcome data, as well as consent for neurologic outcome assessments up to 1 year post–cardiac arrest. Hospital discharge and neurologic status were obtained from public records and/or medical records up until the time consent was formally denied, in accordance with federal regulations and guidance. Local institutional review boards also allowed medical records review for cases where consent was neither obtained nor declined despite multiple consent attempts. Patient demographic, cardiac arrest, and clinical outcome characteristics were analyzed in univariate multinomial regression models, with consent status (obtained, denied, neither obtained nor denied) as the dependent variable. A multivariate multinomial logistic regression was then performed. An exploratory secondary analysis following the same process was performed after assigning patients who neither consented nor declined to the declined consent group. Results Among a total study population of 1,655 cardiac arrest subjects, 457 were transported and had consent attempted (27.6%). The survival status and neurologic function at the time of hospital discharge were known in 440 of 457 (96%) subjects. In the multivariate analysis, initial rhythm of ventricular fibrillation/ventricular tachycardia (VF/VT) and survival with good neurologic outcome were strong predictors of obtaining consent (odds ratio [OR] = 3.15, 95% confidence interval [CI] = 1.73 to 5.75; OR = 7.64, 95% CI = 2.28 to 25.63, respectively). The exploratory secondary analysis also showed initial rhythm of VF/VT and survival with good neurologic outcome as strong predictors of obtaining consent (OR = 1.86, 95% CI = 1.17 to 2.95; OR = 4.52, 95% CI = 2.21 to 9.26, respectively). Conclusions Initial arrest rhythm and survival with good neurologic outcome were highly predictive of obtaining consent in this cardiac arrest trial. This phenomenon could result in underrepresentation of outcome data in the study arm with the worse outcome and represents a significant potential confounder in studies performed under 21 § CFR 50.24. Future revisions to the exception from informed consent regulations should allow access to critical survival data recorded as part of standard documentation, regardless of patient consent status.