Active Decompression during Automated Head-up Cardiopulmonary Resuscitation.

BACKGROUND: The combination of active compression-decompression cardiopulmonary resuscitation (ACD-CPR) with an impedance threshold device (ITD) and controlled head-up positioning (AHUP-CPR) is associated with improved outcomes compared with conventional CPR (C-CPR). This study focused on the role of active decompression (AD) during AHUP-CPR. METHODS: Farm pigs (n=10, ∼40 kg) were anesthetized, intubated and ventilated. Physiological parameters and right ventricular pressure-volume loops were recorded continuously. Ventricular fibrillation was induced and left untreated for 10 mins, followed by automated C-CPR (2 min), ACD+ITD CPR in the flat position (2 min), and then AHUP-CPR with 3 cm of lift above the neutral chest position. After 15 minutes of CPR, AD was discontinued and then restarted incrementally to 4 cm. Data were analyzed with a linear mixed-effects model, using random intercepts for individual pigs. RESULTS: Upon cessation of AD during AHUP-CPR, decompression right atrial pressure (+59%) increased (p<0.01), whereas multiple hemodynamic parameters positively associated with perfusion, including coronary (-25%) and cerebral perfusion pressures (-11%), end-tidal CO2 (-13%), stroke volume and cardiac output (-26%), decreased immediately and significantly with p<0.05. Restoration of AD reduced right atrial pressure and increased positive perfusion parameters in an incremental manner. Only with ≥3 cm of AD were all hemodynamic parameters restored to ≥90% of pre-AD discontinuation levels. CONCLUSION: Full chest wall lift, achieved with ≥3 cm of AD, was needed to maintain and optimize hemodynamics during AHUP-CPR in pigs. These findings should be considered when optimizing care with this new approach.

The association of regional cerebral oximetry and neurologically intact survival in a porcine model of cardiac arrest.

Background: The objective of this study was to determine if regional cerebral oximetry (rSO2) assessed during CPR would be predictive of survival with favorable neurological function in a prolonged model of porcine cardiac arrest. This study also examined the relative predictive value of rSO2 and end-tidal carbon dioxide (ETCO2), separately and together. Methods: This study is a post-hoc analysis of data from a previously published study that compared conventional CPR (C-CPR) and automated head-up positioning CPR (AHUP-CPR). Following 10 min of untreated ventricular fibrillation, 14 pigs were treated with either C-CPR (C-CPR) or AHUP-CPR. rSO2, ETCO2, and other hemodynamic parameters were measured continuously. Pigs were defibrillated after 19 min of CPR. Neurological function was assessed 24 h later. Results: There were 7 pigs in the neurologically intact group and 7 pigs in the poor outcomes group. Within 6 min of starting CPR, the mean difference in rSO2 by 95% confidence intervals between the groups became statistically significant (p < 0.05). The receiver operating curve for rSO2 to predict survival with favorable neurological function reached a maximal area under the curve value after 6 min of CPR (1.0). The correlation coefficient between rSO2 and ETCO2 during CPR increased towards 1.0 over time. The combined predictive value of both parameters was similar to either parameter alone. Conclusion: Significantly higher rSO2 values were observed within less than 6 min after starting CPR in the pigs that survived versus those that died. rSO2 values were highly predictive of survival with favorable neurological function.

Hemodynamics, survival and neurological function with early versus delayed automated head-up CPR in a porcine model of prolonged cardiac arrest.

AIM: To determine if controlled head and thorax elevation, active compression-decompression cardiopulmonary resuscitation (CPR), and an impedance threshold device combined, termed automated head-up positioning CPR (AHUP-CPR), should be initiated early, as a basic (BLS) intervention, or later, as an advanced (ALS) intervention, in a severe porcine model of cardiac arrest. METHODS: Yorkshire pigs (n = 22) weighing ∼40 kg were anesthetized and ventilated. After 15 minutes of untreated ventricular fibrillation, pigs were randomized to AHUP-CPR for 25 minutes (BLS group) or conventional CPR for 10 minutes, followed by 15 minutes of AHUP-CPR (ALS group). Thereafter, epinephrine, amiodarone, and defibrillation were administered. Neurologic function, the primary endpoint, was assessed 24-hours later with a Neurological Deficit Score (NDS, 0 = normal and 260 = worst deficit score or death). Secondary outcomes included return of spontaneous circulation (ROSC), cumulative survival, hemodynamics and epinephrine responsivity. Data, expressed as mean ± standard deviation, were compared using Fisher's Exact, log-rank, Mann-Whitney U and unpaired t-tests. RESULTS: ROSC was achieved in 10/11 pigs with early AHUP-CPR versus 6/11 with delayed AHUP-CPR (p = 0.14), and cumulative 24-hour survival was 45.5% versus 9.1%, respectively (p < 0.02). The NDS was 203 ± 80 with early AHUP-CPR versus 259 ± 3 with delayed AHUP-CPR (p = 0.035). ETCO2, rSO2, and responsiveness to epinephrine were significantly higher in the early versus delayed AHUP-CPR. CONCLUSION: When delivered early rather than late, AHUP-CPR resulted in significantly increased hemodynamics, 24-hour survival, and improved neurological function in pigs after prolonged cardiac arrest. Based on these findings, AHUP-CPR should be considered a BLS intervention.

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.

Development of a Non-invasive Cerebrovascular Status Algorithm to Estimate Cerebral Perfusion Pressure and Intracranial Pressure in a Porcine Model of Focal Brain Injury.

Background: New tools for diagnosis, monitoring, and treatment of elevated intracranial pressure (ICP) or compromised cerebral perfusion pressure (CPP) are urgently needed to improve outcomes after brain injury. Previous success in applying advanced data analytics to build precision monitors based on large, noisy sensor datasets suggested applying the same approach to monitor cerebrovascular status. In these experiments, a new algorithm was developed to estimate ICP and CPP using the arterial pressure waveform. Methods: Sixty-five porcine subjects were subjected to a focal brain injury to simulate a mass lesion with elevated ICP. The arterial pressure waveform and the measured ICP from these subjects during injury and treatment were then utilized to develop and calibrate an ICP and CPP estimation algorithm. These estimation algorithms were then subsequently evaluated on 14 new subjects. Results: The root mean square difference between actual ICP and estimated ICP was 2.0961 mmHg. The root mean square difference between the actual CPP and the estimated CPP was 2.6828 mmHg. Conclusion: A novel ICP or CPP monitor based on the arterial pressure signal produced a very close approximation to actual measured ICP and CPP and warrants further evaluation.

Correlation of end tidal carbon dioxide, amplitude spectrum area, and coronary perfusion pressure in a porcine model of 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 < 0.05). This study established a moderate positive correlation between ETCO2 and AMSA These findings provide the physiological basis for developing and testing a novel noninvasive method that utilizes either ETCO2 alone or the combination of ETCO2 and AMSA to predict when defibrillation might be successful.

Chest compliance is altered by static compression and decompression as revealed by changes in anteroposterior chest height during CPR using the ResQPUMP in a human cadaver model.

INTRODUCTION: Chest compliance plays a fundamental role in the generation of circulation during cardiopulmonary resuscitation (CPR). To study potential changes in chest compliance over time, anterior posterior (AP) chest height measurements were performed on newly deceased (never frozen) human cadavers during CPR before and after 5min of automated CPR. We tested the hypothesis that after 5min of CPR chest compliance would be significantly increased. METHODS: Static compression (30, 40, and 50kg) and decompression forces (-10, -15kg) were applied with a manual ACD-CPR device (ResQPUMP, ZOLL) before and after 5min of automated CPR. Lateral chest x-rays were obtained with multiple reference markers to assess changes in AP distance. RESULTS: In 9 cadavers, changes (mean±SD) in the AP distance (cm) during the applied forces were 2.1±1.2 for a compression force of 30kg, 2.9±1.3 for 40kg, 4.3±1.0 for 50kg, 1.0±0.8 for a decompression force of -10kg and 1.8±0.6 for -15kg. After 5min of automated CPR, AP excursion distances were significantly greater (p<0.05). AP distance increased to 3.7±1.4 for a compression force of 30kg, 4.9±1.6 for 40kg, 6.3±1.9 for 50kg, 2.3±0.9 for -10kg of lift and 2.7±1.1 for -15kg of lift. CONCLUSIONS: These data demonstrate chest compliance increases significantly over time as demonstrated by the significant increase in the measured AP distance after 5min of CPR. These findings suggest that adjustments in compression and decompression forces may be needed to optimize CPR over time.

Reperfusion injury protection during Basic Life Support improves circulation and survival outcomes in a porcine model of prolonged cardiac arrest.

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.

The Effect of Head Up Cardiopulmonary Resuscitation on Cerebral and Systemic Hemodynamics.

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° (15cm) (HUP) and the heart 10° (4cm) or remain in the supine (SUP) flat position during CPR. After 8minutes of untreated ventricular fibrillation and 2minutes of SUP CPR, pigs were randomized to HUP or SUP CPR for 20 more minutes. In Group A, pigs were randomized after 2minutes of flat automated conventional (C) CPR to HUP (n=7) or SUP (n=7) C-CPR. In Group B, pigs were randomized after 2minutes 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 22minutes of CPR, CerPP was 6±3mmHg 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 22minutes 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.

Effect of regulating airway pressure on intrathoracic pressure and vital organ perfusion pressure during cardiopulmonary resuscitation: a non-randomized interventional cross-over study.

BACKGROUND: The objective of this investigation was to evaluate changes in intrathoracic pressure (Ppl), airway pressure (Paw) and vital organ perfusion pressures during standard and intrathoracic pressure regulation (IPR)-assisted cardiopulmonary resuscitation (CPR). METHODS: Multiple CPR interventions were assessed, including newer ones based upon IPR, a therapy that enhances negative intrathoracic pressure after each positive pressure breath. Eight anesthetized pigs underwent 4 min of untreated ventricular fibrillation followed by 2 min each of sequential interventions: (1) conventional standard CPR (STD), (2) automated active compression decompression (ACD) CPR, (3) ACD+ an impedance threshold device (ITD) CPR or (4) ACD+ an intrathoracic pressure regulator (ITPR) CPR, the latter two representing IPR-based CPR therapies. Intrapleural (Ppl), airway (Paw), right atrial, intracranial, and aortic pressures, along with carotid blood flow and end tidal CO2, were measured and compared during each CPR intervention. RESULTS: The lowest mean and decompression phase Ppl were observed with IPR-based therapies [Ppl mean (mean ± SE): STD (0.8 ± 1.1 mmHg); ACD (-1.6 ± 1.6); ACD-ITD (-3.7 ± 1.5, p < 0.05 vs. both STD and ACD); ACD-ITPR (-7.0 ± 1.9, p < 0.05 vs. both STD and ACD)] [Ppl decompression (mean ± SE): STD (-6.3 ± 2.2); ACD (-13.0 ± 3.8); ACD-ITD -16.9 ± 3.6, p < 0.05 vs. both STD and ACD); ACD-ITPR -18.7 ± 3.5, p < 0.05 vs. both STD and ACD)]. Interventions with the lower mean or decompression phase Ppl also demonstrated lower Paw and were associated with higher vital organ perfusion pressures. CONCLUSIONS: IPR-based CPR methods, specifically ACD-ITPR, yielded the most pronounced reduction in both Ppl and Paw and resulted in the most favorable augmentation of hemodynamics during CPR.

Evaluation of Zoll Medical's ResQCPR System for cardiopulmonary resuscitation.

Cardiac arrest remains a leading cause of death, currently affecting more than 250,000 Americans annually. As recommended by the American Heart Association, the current standard of care for patients with an out-of-hospital cardiac arrest (OHCA) includes manual cardiopulmonary resuscitation (S-CPR). Survival with favorable neurological function for all patients following OHCA and treated with S-CPR averages <6%. The ResQCPR System is intended to provide greater circulation to the heart and brain compared with S-CPR, thereby increasing the likelihood of survival. A recent Phase III, multicenter randomized study demonstrated a 50% increase in survival to hospital discharge with favorable neurologic function in subjects with an OHCA of presumed cardiac etiology treated with the ResQCPR System compared with conventional CPR. The ResQCPR System has been recently approved by the FDA as a CPR adjunct to improve the likelihood of survival in adult patients with non-traumatic cardiac arrest.

Enhanced perfusion during advanced life support improves survival with favorable neurologic function in a porcine model of refractory cardiac arrest.

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

Intrathoracic Pressure Regulation Improves Cerebral Perfusion and Cerebral Blood Flow in a Porcine Model of Brain Injury.

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.

Tilting for perfusion: head-up position during cardiopulmonary resuscitation improves brain flow in a porcine model of cardiac arrest.

INTRODUCTION: Cerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT). METHODS: Twenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5min of L-CPR+ITD at 0° supine, 5min at 30° HUT, and then 5min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR+ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT. RESULTS: Coronary perfusion pressure was 19±2mmHg at 0° vs. 30±3 at 30° HUT (p<0.001) and 10±3 at 30° HDT (p<0.001). Cerebral perfusion pressure was 19±3 at 0° vs. 35±3 at 30° HUT (p<0.001) and 4±4 at 30° HDT (p<0.001). Brain-blood flow was 0.19±0.04mlmin(-1)g(-1) at 0° vs. 0.27±0.04 at 30° HUT (p=0.01) and 0.14±0.06 at 30° HDT (p=0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21±2, 16±2, 10±2, 5±2, 0±2, -5±2 respectively, (p<0.001), CerPP increased linearly (p=0.001), and CPP remained constant. CONCLUSION: During CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.

Biphasic intra-thoracic pressure regulation augments cardiac index during porcine peritonitis: a feasibility study.

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.

Awakening after cardiac arrest and post resuscitation hypothermia: are we pulling the plug too early?

BACKGROUND: Time to awakening after out-of-hospital cardiac arrest (OHCA) and post-resuscitation therapeutic hypothermia (TH) varies widely. We examined the time interval from when comatose OHCA patients were rewarmed to 37°C to when they showed definitive signs of neurological recovery and tried to identify potential predictors of awakening. METHODS: With IRB approval, a retrospective case study was performed in OHCA patients who were comatose upon presentation to a community hospital during 2006-2010. They were treated with TH (target of 33°C) for 24h, rewarmed, and discharged alive. Comatose patients were generally treated medically after TH for at least 48h before any decision to withdraw supportive care was made. Pre-hospital TH was not used. Data are expressed as medians and interquartile range. RESULTS: The 89 patients treated with TH in this analysis were divided into three groups based upon the time between rewarming to 37°C and regaining consciousness. The 69 patients that regained consciousness in ≤48h after rewarming were termed "early-awakeners". Ten patients regained consciousness 48-72h after rewarming and were termed "intermediate-awakeners". Ten patients remained comatose and apneic >72h after rewarming but eventually regained consciousness; they were termed "late-awakeners". The ages for the early, intermediate and late awakeners were 56 [49,65], 62 [48,74], and 58 [55,65] years, respectively. Nearly 67% were male. Following rewarming, the time required to regain consciousness for the early, intermediate and late awakeners was 9 [2,18] (range 0-47), 60.5 [56,64.5] (range 49-71), and 126 [104,151]h (range 73-259), respectively. Within 90 days of hospital admission, favorable neurological function based on a Cerebral Performance Category (CPC) score of 1 or 2 was reported in 67/69 early, 10/10 intermediate, and 8/10 late awakeners. CONCLUSION: Following OHCA and TH, arbitrary withdrawal of life support <48h after rewarming may prematurely terminate life in many patients with the potential for full neurological recovery. Additional clinical markers that correlate with late awakening are needed to better determine when withdrawal of support is appropriate in OHCA patients who remain comatose >48h after rewarming.

Induction, maintenance, and reversal of therapeutic hypothermia with an esophageal heat transfer device.

AIM OF THE STUDY: To evaluate a novel esophageal heat transfer device for use in inducing, maintaining, and reversing hypothermia. We hypothesized that this device could successfully induce, maintain (within a 1 °C range of goal temperature), and reverse, mild therapeutic hypothermia in a large animal model over a 30-h treatment protocol. METHODS: Five female Yorkshire swine, weighing a mean of 65 kg (range 61-70) kg each, were anesthetized with inhalational isoflurane via endotracheal intubation and instrumented. The esophageal device was connected to an external chiller and then placed into the esophagus and connected to wall suction. Reduction to goal temperature was achieved by setting the chiller to cooling mode, and a 24h cooling protocol was completed before rewarming and recovering the animals. Histopathologic analysis was scheduled for 3-14 days after protocol completion. RESULTS: Average baseline temperature for the 5 animals was 38.6 °C (range 38.1-39.2 °C). All swine were cooled successfully, with average rate of temperature decrease of 1.3 °C/h (range 1.1-1.9) °C/h. Standard deviation from goal temperature averaged 0.2 °C throughout the steady-state maintenance phase, and no treatment for shivering was necessary during the protocol. Histopathology of esophageal tissue showed no adverse effects from the device. CONCLUSION: A new esophageal heat transfer device successfully and safely induced, maintained, and reversed therapeutic hypothermia in large swine. Goal temperature was maintained within a narrow range, and thermogenic shivering did not occur. These findings suggest a useful new modality to induce therapeutic hypothermia.

"Fluidless" resuscitation with permissive hypotension via impedance threshold device therapy compared with normal saline resuscitation in a porcine model of severe hemorrhage.

BACKGROUND: One approach to improve outcomes after trauma and hemorrhage is to follow the principles of permissive hypotension by avoiding intravascular overpressure and thereby preventing dislodgement of platelet plugs early in the clotting process. We hypothesized that augmentation of negative intrathoracic pressure (nITP) by treatment with an impedance threshold device would improve hemodynamics without compromising permissive hypotension or causing hemodilution, whereas aggressive fluid resuscitation with normal saline (NS) would result in hemodilution and SBPs that are too high for permissive hypotension and capable of clot dislodgement. METHODS: Thirty-four spontaneously breathing anesthetized female pigs (30.6 ± 0.5 kg) were subjected to a fixed 55% hemorrhage over 30 minutes; block randomized to nITP, no treatment, or intravenous bolus of 1-L NS; and evaluated over 30 minutes. Results are reported as mean ± SEM. RESULTS: Average systolic blood pressures (SBPs) (mm Hg) 30 minutes after the study interventions were as follows: nITP, 82.1 ± 2.9; no treatment, 69.4 ± 4.0; NS 89.3 ± 5.2. Maximum SBPs during the initial 15 minutes of treatment were as follows: nITP, 88.0 ± 4.3; no treatment, 70.8 ± 4.3; and NS, 131 ± 7.6. After 30 minutes, mean pulse pressure (mm Hg) was significantly higher in the nITP group (nITP, 32.3 ± 2.2) versus the no-treatment group (21.5 ± 1.5 controls) (p < 0.05), and the mean hematocrit was 25.2 ± 0.8 in the nITP group versus 19 ± 0.6 in the NS group (p < 0.001). CONCLUSION: In this porcine model of hemorrhagic shock, nITP therapy significantly improved SBP and pulse pressure for 30 minutes without overcompensation compared with controls with no treatment. By contrast, aggressive fluid resuscitation with NS but not nITP resulted in a significant rise in SBP to more than 100 mm Hg within minutes of initiating therapy that could cause a further reduction in hematocrit and clot dislodgment.

Use of respiratory impedance in prehospital care of hypotensive patients associated with hemorrhage and trauma: a case series.

BACKGROUND: The respiratory pump can be optimized to enhance circulation in patients with hypotension by having patients spontaneously breathe through a low level of inspiratory resistance. This can be achieved with an impedance threshold device (ITD) designed to provide 7 cm H2O resistance during spontaneous inspiration with minimal resistance during expiration. Little is known about the effects of harnessing this physiological concept to increase blood pressure (BP) in the prehospital setting of care for patients with hypotension caused by blood loss or trauma. In this case series, we report on the feasibility, effectiveness, and safety of rapidly deploying the ITD by first responders to treat hypotension secondary to blood loss and trauma in the urban setting by emergency medical services personnel. METHODS: Hemodynamic data from hypotensive patients (pretreatment systolic BP [SBP] <100 mm Hg) from 3 U.S. cities where the ITD is deployed were evaluated. The primary end point was maximum change in SBP and diastolic BP (DBP) from before to during ITD use in patients with hypotension secondary to documented blood loss or trauma. Secondary end points were device tolerance, whether the patient felt "better," change in heart rate, O2 saturation, and adverse events. RESULTS: Of the 255 hypotensive patients treated, there were 26 categorized with blood loss and 13 with trauma. In this 39-patient subgroup, the SBP and DBP (mean ± SD) increased from 79 ± 14 mm Hg and 48 ± 12 mm Hg before ITD placement to 110 ± 17 mm Hg and 66 ± 14 mm Hg after ITD placement (p < 0.001). Breathing through the ITD resulted in no reported adverse events, was well tolerated, and resulted in feeling "better" in more than 85% of the patients. CONCLUSION: Use of an ITD by emergency medical services personnel on hypotensive spontaneously breathing patients secondary to blood loss and trauma increased SBP and DBP and was feasible, well tolerated, and not associated with adverse effects (e.g., increased bleeding).