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.

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.

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.

Improved cerebral perfusion pressures and 24-hr neurological survival in a porcine model of cardiac arrest with active compression-decompression cardiopulmonary resuscitation and augmentation of negative intrathoracic pressure.

OBJECTIVE: Generation of negative intrathoracic pressure during the decompression phase of cardiopulmonary resuscitation enhances the refilling of the heart. We tested the hypothesis that when compared with closed-chest manual compressions at 80 chest compressions per min, treatment with active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min combined with augmentation of negative intrathoracic pressure would lower intracranial pressure and increase cerebral perfusion, thereby improving neurologically intact survival rates following prolonged untreated cardiac arrest. DESIGN: Prospective, randomized animal study. SETTING: Animal laboratory facilities. SUBJECTS: A total of 26 female farm pigs in two different protocols (n = 17 and n = 9). INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: Seventeen pigs were subjected to 8.5 mins of untreated ventricular fibrillation and prospectively randomized to cardiopulmonary resuscitation at 80 chest compressions/min or active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min plus an impedance threshold device. Coronary perfusion pressures (29.5 ± 2.7 mm Hg vs. 22.4 ± 1.6 mm Hg, p = .03), carotid blood flow (44.0 ± 12.2 vs. 30.9 ± 10.4, p = .03), and 24-hr neurological survival (88% vs. 22%, p = .015) were higher with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device. Cerebral perfusion pressures, measured in nine additional pigs, were improved with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device (21.9 ± 1.2 mm Hg vs. 8.9 ± 0.8 mm Hg, p < .0001). With active compression-decompression cardiopulmonary resuscitation + impedance threshold device, mean diastolic intracranial pressure during decompression was lower (12.2 ± 0.2 mm Hg vs. 16.6 ± 1.2 mm Hg, p = .02) and the downward slope of the decompression phase intracranial pressure curve was steeper (-60.3 ± 12.9 mm Hg vs. -46.7 ± 11.1 mm Hg/sec, p < .001). CONCLUSIONS: Active compression-decompression cardiopulmonary resuscitation + an impedance threshold device increased cerebral perfusion pressures and lowered diastolic intracranial pressure and intracranial pressure rate during the decompression phase. These mechanisms may underlie the observed increase in cerebral perfusion pressure, carotid blood flow, and survival rates with favorable neurologic outcomes in this pig model of cardiac arrest.

An impedance threshold device increases blood pressure in hypotensive patients.

BACKGROUND: The impedance threshold device (ITD-7) augments the vacuum created in the thorax with each inspiration, thereby enhancing blood flow from the extrathoracic venous systems into the heart. OBJECTIVES: To the best of our knowledge, the ITD-7 has not previously been investigated in hypotensive patients in the emergency department (ED) or the prehospital setting. The objective of this study was to determine whether the ITD-7 would increase systolic arterial pressures in hypotensive spontaneously breathing patients. METHODS: The ED study was a prospective, randomized, double-blind, sham control design. Patients with a systolic blood pressure ≤ 95 mm Hg were randomized to breathe for 10 min through an active or sham ITD. The primary endpoint was the change in systolic blood pressure measured non-invasively. The prehospital study was a prospective, non-blinded evaluation of the ITD-7 in hypotensive patients. RESULTS: In the ED study, the mean ± standard deviation rise in systolic blood pressure was 12.9 ± 8.5 mm Hg for patients (n = 16) treated with an active ITD-7 vs. 5.9 ± 5.9 mm Hg for patients (n = 18) treated with a sham ITD-7 (p < 0.01). In the prehospital study, the mean systolic blood pressure before the ITD-7 was 79.4 ± 10.2 mm Hg and 107.3 ± 17.6 mm Hg during ITD-7 use (n = 47 patients) (p < 0.01). CONCLUSION: During this clinical evaluation of the ITD-7 for the treatment of hypotensive patients in the ED and in the prehospital setting, use of the device significantly increased systolic blood pressure and was safe and generally well tolerated.

Comparison of a 10-breaths-per-minute versus a 2-breaths-per-minute strategy during cardiopulmonary resuscitation in a porcine model of cardiac arrest.

BACKGROUND: Hyperventilation during cardiopulmonary resuscitation (CPR) is harmful. METHODS: We tested the hypotheses that, during CPR, 2 breaths/min would result in higher cerebral perfusion pressure and brain-tissue oxygen tension than 10 breaths/min, and an impedance threshold device (known to increase circulation) would further enhance cerebral perfusion and brain-tissue oxygen tension, especially with 2 breaths/min. RESULTS: Female pigs (30.4 +/- 1.3 kg) anesthetized with propofol were subjected to 6 min of untreated ventricular fibrillation, followed by 5 min of CPR (100 compressions/min, compression depth of 25% of the anterior-posterior chest diameter), and ventilated with either 10 breaths/min or 2 breaths/min, while receiving 100% oxygen and a tidal volume of 12 mL/kg. Brain-tissue oxygen tension was measured with a probe in the parietal lobe. The impedance threshold device was then used during an 5 additional min of CPR. During CPR the mean +/- SD calculated coronary and cerebral perfusion pressures with 10 breaths/min versus 2 breaths/min, respectively, were 17.6 +/- 9.3 mm Hg versus 14.3 +/- 6.5 mm Hg (p = 0.20) and 16.0 +/- 9.5 mm Hg versus 9.3 +/- 12.5 mm Hg (p = 0.25). Carotid artery blood flow, which was prospectively designated as the primary end point, was 65.0 +/- 49.6 mL/min in the 10-breaths/min group, versus 34.0 +/- 17.1 mL/min in the 2-breaths/min group (p = 0.037). Brain-tissue oxygen tension was 3.0 +/- 3.3 mm Hg in the 10-breaths/min group, versus 0.5 +/- 0.5 mm Hg in the 2-breaths/min group (p = 0.036). After 5 min of CPR there were no significant differences in arterial pH, PO2, or PCO2 between the groups. During CPR with the impedance threshold device, the mean carotid blood flow and brain-tissue oxygen tension in the 10-breaths/min group and the 2-breaths/min group, respectively, were 102.5 +/- 67.9 mm Hg versus 38.8 +/- 23.7 mm Hg (p = 0.006) and 4.5 +/- 6.0 mm Hg versus 0.7 +/- 0.7 mm Hg (p = 0.032). CONCLUSIONS: Contrary to our initial hypothesis, during the first 5 min of CPR, 2 breaths/min resulted in significantly lower carotid blood flow and brain-tissue oxygen tension than did 10 breaths/min. Subsequent addition of an impedance threshold device significantly enhanced carotid flow and brain-tissue oxygen tension, especially in the 10-breaths/min group.