Scott McKnite

Hyperventilation-Induced Hypotension During Cardiopulmonary Resuscitation

Background—A clinical observational study revealed that rescuers consistently hyperventilated patients during out-of-hospital cardiopulmonary resuscitation (CPR). The objective of this study was to quantify the degree of excessive ventilation in humans and determine if comparable excessive ventilation rates during CPR in animals significantly decrease coronary perfusion pressure and survival. Methods and Results—In humans, ventilation rate and duration during CPR was electronically recorded by professional rescuers. In 13 consecutive adults (average age, 63±5.8 years) receiving CPR (7 men), average ventilation rate was 30±3.2 per minute (range, 15 to 49). Average duration per breath was 1.0±0.07 per second. No patient survived. Hemodynamics were studied in 9 pigs in cardiac arrest ventilated in random order with 12, 20, or 30 breaths per minute. Survival rates were then studied in 3 groups of 7 pigs in cardiac arrest that were ventilated at 12 breaths per minute (100% O2), 30 breaths per minute (100% O2), or 30 breaths per minute (5% CO2/95% O2). In animals treated with 12, 20, and 30 breaths per minute, the mean intrathoracic pressure (mm Hg/min) and coronary perfusion pressure (mm Hg) were 7.1±0.7, 11.6±0.7, 17.5±1.0 (P <0.0001), and 23.4±1.0, 19.5±1.8, and 16.9±1.8 (P =0.03), respectively. Survival rates were 6/7, 1/7, and 1/7 with 12, 30, and 30+ CO2 breaths per minute, respectively (P =0.006). Conclusions—Professional rescuers were observed to excessively ventilate patients during out-of-hospital CPR. Subsequent animal studies demonstrated that similar excessive ventilation rates resulted in significantly increased intrathoracic pressure and markedly decreased coronary perfusion pressures and survival rates.

Improving Active Compression-Decompression Cardiopulmonary Resuscitation With an Inspiratory Impedance Valve

BACKGROUND Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) has recently been demonstrated to provide significantly more blood flow to vital organs during cardiac arrest. To further enhance the effectiveness of this technique, we tested the hypothesis that intermittent impedance to inspiratory gas exchange during the decompression phase of ACD CPR enhances vital organ blood flow. METHODS AND RESULTS ACD CPR was performed with a pneumatically driven automated compression-decompression device in a porcine model of ventricular fibrillation (VF). Nine pigs were randomized to receive ACD CPR alone, while 8 pigs received ACD CPR plus intermittent impedance to inspiratory gas exchange with a threshold valve set to 40 cm H2O. Results comparing 2 minutes of ACD CPR alone versus ACD CPR with the inspiratory impedance threshold valve (ITV) revealed significantly higher mean (+/- SEM) coronary perfusion pressures (diastolic aortic minus diastolic right atrial pressures) in the ITV (31.0 +/- 2.3 mm Hg) group versus with ACD CPR alone (21 +/- 3.6 mm Hg) (P < .05). Total left ventricular and cerebral blood flows, determined by radiolabeled microspheres, were 0.77 +/- 0.095 and 0.47 +/- 0.06 mL/min per gram, respectively, with ACD CPR plus the ITV versus 0.45 +/- 0.1 and 0.32 +/- 0.016 mL/min per gram, respectively, with ACD CPR alone (P < .05). Similar improvements in the ITV group were observed after 7 minutes of ACD CPR. After 16 minutes of VF and 13 minutes of ACD CPR, 6 of 8 pigs in the ITV group were successfully resuscitated with less than three successive 150-J shocks, whereas only 2 of 9 pigs with ACD CPR alone were resuscitated with equivalent energy levels (P < .02). With up to three additional and successive 200-J shocks, all pigs in the ITV group and 7 of 9 pigs with ACD CPR alone were resuscitated (P = .18). CONCLUSIONS Intermittent impedance to inspiratory flow of respiratory gases during ACD CPR significantly improves coronary perfusion pressures and vital organ blood flow and lowers defibrillation energy requirements in a porcine model of VF.

Clinical and hemodynamic comparison of 15: 2 and 30:2 compression-to- ventilation ratios for cardiopulmonary resuscitation

Objective:To compare cardiopulmonary resuscitation (CPR) with a compression to ventilation (C:V) ratio of 15:2 vs. 30:2, with and without use of an impedance threshold device (ITD). Design:Prospective randomized animal and manikin study. Setting:Animal laboratory and emergency medical technician training facilities. Subjects:Twenty female pigs and 20 Basic Life Support (BLS)-certified rescuers. Interventions, Measurements, and Main Results: Animals:Acid-base status, cerebral, and cardiovascular hemodynamics were evaluated in 18 pigs in cardiac arrest randomized to a C:V ratio of 15:2 or 30:2. After 6 mins of cardiac arrest and 6 mins of CPR, an ITD was added. Compared to 15:2, 30:2 significantly increased diastolic blood pressure (20 ± 1 to 26 ± 1; p < .01); coronary perfusion pressure (18 ± 1 to 25 ± 2; p = .04); cerebral perfusion pressure (16 ± 3 to 18 ± 3; p = .07); common carotid blood flow (48 ± 5 to 82 ± 5 mL/min; p < .001); end-tidal CO2 (7.7 ± 0.9 to 15.7 ± 2.4; p < .0001); and mixed venous oxygen saturation (26 ± 5 to 36 ± 5, p < .05). Hemodynamics improved further with the ITD. Oxygenation and arterial pH were similar. Only one of nine pigs had return of spontaneous circulation with 15:2, vs. six of nine with 30:2 (p < 0.03). Humans: Fatigue and quality of CPR performance were evaluated in 20 BLS-certified rescuers randomized to perform CPR for 5 mins at 15:2 or 30:2 on a recording CPR manikin. There were no significant differences in the quality of CPR performance or measurement of fatigue. Significantly more compressions per minute were delivered with 30:2 in both the animal and human studies. Conclusions:These data strongly support the contention that a ratio of 30:2 is superior to 15:2 during manual CPR and that the ITD further enhances circulation with both C:V ratios.

Improving Standard Cardiopulmonary Resuscitation with an Inspiratory Impedance Threshold Valve in a Porcine Model of Cardiac Arrest

To improve the efficiency of standard cardiopulmonary resuscitation (CPR), we evaluated the potential value of impeding respiratory gas exchange selectively during the decompression phase of standard CPR in a porcine model of ventricular fibrillation. After 6 min of untreated cardiac arrest, anesthetized farm pigs weighing 30 kg were randomized to be treated with either standard CPR with a sham valve (n = 11) or standard CPR plus a functional inspiratory impedance threshold valve (ITV™) (n = 11). Coronary perfusion pressure (CPP) (diastolic aortic minus right atrial pressure) was the primary endpoint. Vital organ blood flow was assessed with radiolabeled microspheres after 6 min of CPR, and defibrillation was attempted 11 min after starting CPR. After 2 min of CPR, mean ± sem CPP was 14 ± 2 mm Hg with the sham valve versus 20 ± 2 mm Hg in the ITV group (P < 0.006). Significantly higher CPPs were maintained throughout the study when the ITV was used. After 6 min of CPR, mean ± sem left ventricular and global cerebral blood flows were 0.10 ± 0.03 and 0.19 ± 0.03 mL · min−1 · g−1 in the Control group versus 0.19 ± 0.03 and 0.26 ± 0.03 mL · min−1 · g−1 in the ITV group, respectively (P < 0.05). Fifteen minutes after successful defibrillation, 2 of 11 animals were alive in the Control group versus 6 of 11 in the ITV group (not significant). In conclusion, use of an inspiratory impedance valve during standard CPR resulted in a marked increase in CPP and vital organ blood flow after 6 min of cardiac arrest.

Comparison of epinephrine and vasopressin in a pediatric porcine model of asphyxial cardiac arrest.

ObjectiveThis study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest. DesignProspective, randomized laboratory investigation using an established porcine model for measurement of hemodynamic variables, organ blood flow, blood gases, and return of spontaneous circulation. SettingUniversity hospital laboratory. SubjectsEighteen piglets weighing 8–11 kg. InterventionsAsphyxial cardiac arrest was induced by clamping the endotracheal tube. After 8 mins of cardiac arrest and 8 mins of cardiopulmonary resuscitation, a bolus dose of either 0.8 units/kg vasopressin (n = 6), 200 &mgr;g/kg epinephrine (n = 6), or a combination of 45 &mgr;g/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered in a randomized manner. Defibrillation was attempted 6 mins after drug administration. Measurements and Main ResultsMean ± sem coronary perfusion pressure, before and 2 mins after drug administration, was 13 ± 2 and 23 ± 6 mm Hg in the vasopressin group; 14 ± 2 and 31 ± 4 mm Hg in the epinephrine group; and 13 ± 1 and 33 ± 6 mm Hg in the epinephrine-vasopressin group, respectively (p = NS). At the same time points, mean ± sem left ventricular myocardial blood flow was 44 ± 31 and 44 ± 25 mL·min−1·100 g−1 in the vasopressin group; 30 ± 18 and 233 ± 61 mL·min−1·100 g−1 in the epinephrine group; and 36 ± 10 and 142 ± 57 mL·min−1·100 g−1 in the epinephrine-vasopressin group (p < .01 epinephrine vs. vasopressin;p < .02 epinephrine-vasopressin vs. vasopressin). Total cerebral blood flow trended toward higher values after epinephrine-vasopressin (60 ± 19 mL·min−1·100 g−1) than after vasopressin (36 ± 17 mL·min−1·100 g−1) or epinephrine alone (31 ± 7 mL·min−1·100 g−1;p = .07, respectively). One of six vasopressin, six of six epinephrine, and four of six epinephrine-vasopressin-treated animals had return of spontaneous circulation (p < .01, vasopressin vs. epinephrine). ConclusionsAdministration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation. Return of spontaneous circulation was significantly more likely in epinephrine-treated pigs than in animals resuscitated with vasopressin alone.

Vasopressin improves survival after cardiac arrest in hypovolemic shock.

UNLABELLED Survival after hypovolemic shock and cardiac arrest is dismal with current therapies. We evaluated the potential benefits of vasopressin versus large-dose epinephrine in hemorrhagic shock and cardiac arrest on vital organ perfusion, and the likelihood of resuscitation. In 18 pigs, 35% of the estimated blood volume was withdrawn over 15 min and ventricular fibrillation was induced 5 min later. After 4 min of cardiac arrest and 4 min of standard cardiopulmonary resuscitation, a bolus dose of either 200 microg/kg epinephrine (n = 7), 0.8 unit/kg vasopressin (n = 7), or saline placebo (n = 4) was administered in a blinded, randomized manner. Defibrillation was attempted 2.5 min after drug administration, and all animals were subsequently observed for 1 h without further intervention. Spontaneous circulation was restored in 7 of 7 vasopressin animals, in 6 of 7 epinephrine pigs, and in 0 of 4 placebo swine. At 5 and 30 min after return of spontaneous circulation, median (minimum and maximum) renal blood flow after epinephrine was 2 (0-31), and 2 (0-48) mL. 100 g(-1). min(-1), respectively; and after vasopressin 96 (12-161), and 44 (16-105) mL. 100 g(-1). min(-1), respectively (P: <.01 between groups). Epinephrine animals developed a profound metabolic acidosis by 15 min after return of spontaneous circulation (mean arterial pH, 7.11 +/- 0.01), and by 60 min all epinephrine-treated animals had died. The vasopressin pigs had (P: = 0.015) less acidosis (pH = 7.26+/-0. 04) at corresponding time points, and all survived > or =55 min (P: < 0. 01). In conclusion, treatment of hypovolemic cardiac arrest with vasopressin, but not with large-dose epinephrine or saline placebo, resulted in sustained vital organ perfusion, less metabolic acidosis, and prolonged survival. Based on these findings, clinical evaluation of vasopressin during hypovolemic cardiac arrest may be warranted. IMPLICATIONS The chances of surviving cardiac arrest in hemorrhagic shock are considered dismal without adequate fluid replacement. However, treatment of hypovolemic cardiac arrest with vasopressin, but not with large-dose epinephrine or saline placebo, resulted in sustained vital organ perfusion and prolonged survival in an animal model of suspended infusion therapy.

Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation.

ObjectiveWe 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. DesignProspective, randomized laboratory investigation that used an established porcine model for measurement of hemodynamic variables and organ blood flow. SettingUniversity hospital laboratory. SubjectsEighteen piglets weighing 8–11 kg. InterventionsAfter 8 mins of ventricular fibrillation and 8 mins of cardiopulmonary resuscitation, either 0.4 units/kg vasopressin (n = 6), 45 &mgr;g/kg epinephrine (n = 6), or a combination of 45 &mgr;g/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 &mgr;g/kg epinephrine, or a combination of 200 &mgr;g/kg epinephrine with 0.8 units/kg vasopressin was given. Defibrillation was attempted 20 mins after initiating cardiopulmonary resuscitation. Measurements and Main ResultsMean ± sem left ventricular myocardial blood flow 2 mins after each respective drug administration was 65 ± 4 and 70 ± 13 mL·min−1·100 g−1 in the vasopressin group; 83 ± 42 and 85 ± 41 mL·min−1·100 g−1 in the epinephrine group; and 176 ± 32 and 187 ± 29 mL·min−1·100 g−1 in the epinephrine-vasopressin group (p < .006 after both doses of epinephrine-vasopressin vs. vasopressin and after the first dose of epinephrine-vasopressin vs. epinephrine, respectively). At the same times, mean ± sem total cerebral blood flow was 73 ± 3 and 47 ± 5 mL·min−1·100 g−1 after vasopressin; 18 ± 2 and 12 ± 2 mL·min−1·100 g−1 after epinephrine; and 79 ± 21 and 41 ± 8 mL·min−1·100 g−1 after epinephrine-vasopressin (p < .025 after both doses of vasopressin and epinephrine-vasopressin vs. epinephrine). Five of six vasopressin-treated, two of six epinephrine-treated, and six of six epinephrine-vasopressin treated animals had return of spontaneous circulation (nonsignificant). ConclusionsIn this pediatric porcine model of ventricular fibrillation, the combination of epinephrine with vasopressin during cardiopulmonary resuscitation resulted in significantly higher levels of left ventricular myocardial blood flow than either vasopressin alone or epinephrine alone. Both vasopressin alone and the combination of epinephrine with vasopressin, but not epinephrine alone, improved total cerebral blood flow during cardiopulmonary resuscitation. In stark contrast to asphyxial cardiac arrest, vasopressin alone or in combination with epinephrine appears to be of benefit after ventricular fibrillation in the pediatric porcine model.

Intrathoracic Pressure Regulator During Continuous-Chest-Compression Advanced Cardiac Resuscitation Improves Vital Organ Perfusion Pressures in a Porcine Model of Cardiac Arrest

Background—A novel device, the intrathoracic pressure regulator (ITPR), combines an inspiratory impedance threshold device (ITD) with a vacuum source for the generation of controlled −10 mm Hg vacuum in the trachea during cardiopulmonary resuscitation (CPR) while allowing positive pressure ventilation. Compared with standard (STD) CPR, ITPR-CPR will enhance venous return, systemic arterial pressure, and vital organ perfusion in both porcine models of ventricular fibrillation and hypovolemic cardiac arrest. Methods and Results—In protocol 1, 20 pigs (weight, 30±0.5 kg) were randomized to STD-CPR or ITPR-CPR. After 8 minutes of untreated ventricular fibrillation, CPR was performed for 6 minutes at 100 compressions per minute and positive pressure ventilation (100% O2) with a compression-to-ventilation ratio of 15:2. In protocol 2, 6 animals were bled 50% of their blood volume. After 4 minutes of untreated ventricular fibrillation, interventions were performed for 2 minutes with STD-CPR and 2 minutes of ITPR-CPR. This sequence was repeated. In protocol 3, 6 animals after 8 minutes of untreated VF were treated with ITPR-CPR for 15 minutes, and arterial and venous blood gases were collected at baseline and minutes 5, 10, and 15 of CPR. A newer, leak-proof ITPR device was used. Aortic, right atrial, endotracheal pressure, intracranial pressure, and end-tidal CO2 values were measured (mm Hg); common carotid arterial flow also was measured (mL/min). Coronary perfusion pressure (diastolic; aortic minus right atrial pressure) and cerebral perfusion pressure (mean arterial minus mean intracranial pressure) were calculated. Unpaired Student t test and Friedman’s repeated-measures ANOVA of ranks were used in protocols 1 and 3. A 2-tailed Wilcoxon signed-rank test was used for analysis in protocol 2. Fischer’s exact test was used for survival. Significance was set at P<0.05. Vital organ perfusion pressures and end-tidal CO2 were significantly improved with ITPR-CPR in both protocols. In protocol 1, 1-hour survival was 100% with ITPR-CPR and 10% with STD-CPR (P=0.001). Arterial blood pH was significantly lower and Paco2 was significantly higher with ITPR- CPR in protocol 1. Arterial oxygen saturation was 100% throughout the study in both protocols. Paco2 and Pao2 remained stable, but metabolic acidosis progressed, as expected, throughout the 15 minutes of CPR in protocol 3. Conclusions—Compared with STD-CPR, use of ITPR-CPR improved hemodynamics and short-term survival rates after cardiac arrest.

Treatment of hypotension in pigs with an inspiratory impedance threshold device: A feasibility study

Objective:An inspiratory impedance threshold device was evaluated in spontaneously breathing animals with hypotension to determine whether it could help improve systemic arterial pressures when fluid replacement was not immediately available. Design:Prospective, randomized. Setting:Animal laboratory. Subjects:Thirty-nine female farm pigs (weight, 28 –33 kg). Interventions:A total of 39 anesthetized spontaneously breathing pigs were treated with an impedance threshold device, with cracking pressures from 0 to −20 cm H2O. Four separate experimental protocols were performed: protocol A, in which the hemodynamics of seven pigs were examined during application of an impedance threshold device at various levels of inspiratory impedance (−5, −10, −15, and −20 cm H2O), both before and after a severe, controlled hemorrhage to a systolic blood pressure of 50 –55 mm Hg; protocol B, in which nine pigs bled to systolic blood pressure of 50 –55 mm Hg were treated with an impedance threshold device set at −12 cm H2O and were compared with nine others treated with a sham device; protocol C, in which the effects of the impedance threshold device on mixed venous gases were measured in seven hemorrhaged pigs; and protocol D, in which the effects of the impedance threshold device on cardiac output in seven hemorrhaged pigs were measured. Methods and Main Results:During initial studies with both normovolemic and hypovolemic pigs, sequential increases in inspiratory impedance resulted in a significant increase in systolic blood pressure, whereas diastolic left ventricular and right atrial pressures decreased significantly and proportionally to the level of impedance. When comparing the sham vs. active impedance threshold device (−12 cm H2O) in hypotensive pigs, systolic blood pressure (mean ± sem) with active impedance threshold device treatment increased from 70 ± 2 mm Hg to 105 ± 4 mm Hg (p < .01). Pressures in the control group remained at 70 ± 4 mm Hg (p < .01). Cardiac output increased by nearly 25% (p < .01) with the active impedance threshold device when calculated using the mixed gas equation and when determined by thermodilution. Conclusions:These studies demonstrate that it is feasible to use a device that creates inspiratory impedance in spontaneously breathing normotensive and hypotensive pigs to increase blood pressure and enhance cardiopulmonary circulation in the absence of immediate fluid resuscitation. Further studies are needed to evaluate the potential long-term effects and limitations of this new approach to treat hypovolemic hypotension.

No assisted ventilation cardiopulmonary resuscitation and 24-hour neurological outcomes in a porcine model of cardiac arrest

Objectives:To evaluate the effect of no assisted ventilation cardiopulmonary resuscitation on neurologically intact survival compared with ten positive pressure ventilations/minute cardiopulmonary resuscitation in a pig model of cardiac arrest. Design:Prospective randomized animal study. Setting:Animal laboratory. Subjects:Sixteen female intubated pigs (25.2 ± 2.1 kg) anesthetized with propofol. Interventions:fter 8 mins of untreated ventricular fibrillation, the intubated animals were randomized to 8 mins of continuous chest compressions (100/min) and either no assisted ventilation (n = 9) or 10 positive pressure ventilations/min (Smart Resuscitator Bag with 100% O2 flow at 10 L/min) (n = 7). The primary end point, neurologically intact 24-hr survival, was evaluated using a pig cerebral performance category score by a veterinarian blinded to the cardiopulmonary resuscitation method. Measurements, and Main Results:During cardiopulmonary resuscitation, aortic and coronary perfusion pressure were similar between groups but cerebral perfusion pressure was significantly higher in the positive pressure ventilation group (33 ± 15 vs. 14 ± 14, p = .04). After 7.5 mins of cardiopulmonary resuscitation, arterial pO2 (mm Hg) and mixed venous O2 saturation (%) were significantly higher in the positive pressure ventilation compared with the no assisted ventilation group (117 ± 29 and 41 ± 21 vs. 40 ± 24 and 10.8 ± 7; p = .01 for both). Paco2 was significantly lower in the positive pressure ventilation group (48 ± 10 vs. 77 ± 26, p = .01). After 24 hrs, four of nine no assisted ventilation pigs were alive with a mean cerebral performance category score of 3 ± 0 vs. five of seven alive and neurologically intact positive pressure ventilation pigs with a cerebral performance category score of 1 ± 0.3 (p < .001 for cerebral performance category score). Conclusions:No assisted ventilation cardiopulmonary resuscitation results in profound hypoxemia, respiratory acidosis, and significantly worse 24-hr neurologic outcomes compared with positive pressure ventilation cardiopulmonary resuscitation in pigs.