Keith G. Lurie

Evaluation of Different Ventricular Pacing Sites in Patients With Severe Heart Failure Results of an Acute Hemodynamic Study

BACKGROUND Multisite ventricular pacing has recently been proposed as an additional treatment for patients with severe congestive heart failure. To further assess the potential value of this technique, we compared the acute hemodynamic changes associated with pacing the right ventricular apex (RVA) or outflow tract (RVOT) alone, the left ventricle (LV) alone, or biventricular (BIV) pacing of the RVA and LV together. METHODS AND RESULTS Acute hemodynamic findings were measured in 27 patients with severe heart failure despite optimal therapy and either first-degree AV block and/or an intraventricular conduction defect. In the 23 patients with a high pulmonary capillary wedge pressure (PCWP) (>15 mm Hg), data were collected after transvenous pacing at different ventricular sites in either the VDD mode (AV delay=100 ms) or the VVI mode in patients with atrial fibrillation (n=6). The mean baseline cardiac index was 1.82 L x min(-1) x m(-2). Mean+/-SD baseline systolic blood pressure (SBP) (118.5+/-15.2 mm Hg), PCWP (26.4+/-6.6 mm Hg), and V-wave amplitude (39.1+/-14.6 mm Hg) were similar before and after either RVA or RVOT pacing. In contrast, LV-based pacing (either LV alone or BIV pacing) resulted in higher SBP (P<.03) and lower PCWP (P<.01) and V-wave amplitude (P<.001) than either baseline or RV pacing measurements. With LV pacing alone, SBP, PCWP, and V waves were 126.5+/-15.1, 20.7+/-5.9, and 25.5+/-8.1 mm Hg, respectively. The results with LV pacing alone were similar to those obtained with BIV pacing. CONCLUSIONS In patients with severe congestive heart failure, both LV pacing alone and BIV pacing resulted in a similar and significant acute improvement in SBP, PCWP, and V-wave amplitude compared with baseline measurements and RV pacing alone. These results provide a strong basis for initiating long-term studies examining the chronic effects of LV-based pacing in patients with medically refractory congestive heart failure.

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.

Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation

BACKGROUND Studies in animals have suggested that intravenous vasopressin is associated with better vital-organ perfusion and resuscitation rates than is epinephrine in the treatment of cardiac arrest. We did a randomised comparison of vasopressin with epinephrine in patients with ventricular fibrillation in out-of-hospital cardiac arrest. METHODS 40 patients in ventricular fibrillation resistant to electrical defibrillation were prospectively and randomly assigned epinephrine (1 mg intravenously; n = 20) or vasopressin (40 U intravenously; n = 20) as primary drug therapy for cardiac arrest. The endpoints of this double blind study were successful resuscitation (hospital admission), survival for 24 h, survival to hospital discharge and neurological outcome (Glasgow coma scale). Analyses were by intention to treat. FINDINGS Seven (35%) patients in the epinephrine group and 14 (70%) in the vasopressin group survived to hospital admission (p = 0.06). At 24 h, four (20%) epinephrine-treated patients and 12 (60%) vasopressin-treated patients were alive (p = 0.02). Three (15%) patients in the epinephrine group and eight (40%) in the vasopressin group survived to hospital discharge (p = 0.16). Neurological outcomes were similar (mean Glasgow coma score at hospital discharge 10.7 [SE 3.8] vs 11.7 [1.6], p = 0.78). INTERPRETATION In this preliminary study, a significantly larger proportion of patients created with vasopressin than of those treated with epinephrine were resuscitated successfully from out-of-hospital ventricular fibrillation and survived for 24 h. Based upon these findings, larger multicentre studies of vasopressin in the treatment of cardiac arrest are needed.

Death by hyperventilation: A common and life-threatening problem during cardiopulmonary resuscitation

Context:This translational research initiative focused on the physiology of cardiopulmonary resuscitation (CPR) initiated by a clinical observation of consistent hyperventilation by professional rescuers in out-of-hospital cardiac arrest. This observation generated scientific hypotheses that could only ethically be tested in the animal laboratory. Objective:To examine the hypothesis that excessive ventilation rates during performance of CPR by overzealous but well-trained rescue personnel causes a significant decrease in coronary perfusion pressure and an increased likelihood of death. Design and Setting:In the in vivo human aspect of the study, we set out to objectively and electronically record rate and duration of ventilation during performance of CPR by trained professional rescue personnel in a prospective clinical trial in intubated, adult patients with out-of-hospital cardiac arrest. In the in vivo animal aspect of the study, to simulate the clinically observed hyperventilation, nine pigs in cardiac arrest were ventilated in a random order with 12, 20, or 30 breaths/min, and physiologic variables were assessed. Next, three groups of seven pigs in cardiac arrest were ventilated at 12 breaths/min with 100% oxygen, 30 breaths/min with 100% oxygen, or 30 breaths/min with 5% Co2/95% oxygen, and survival was assessed. Main Outcome Measures:Ventilation rate and duration in humans; mean intratracheal pressure, coronary perfusion pressure, and survival rates in animals. Results:In 13 consecutive adults (average age, 63 ± 5.8 yrs) receiving CPR (seven men) the average ventilation rate was 30 ± 3.2 breaths/min (range, 15 to 49 breaths/min) and the average duration of each breath was 1.0 ± 0.07 sec. The average percentage of time in which a positive pressure was recorded in the lungs was 47.3 ± 4.3%. No patient survived. In animals treated with 12, 20, and 30 breaths/min, the mean intratracheal pressures and coronary perfusion pressures were 7.1 ± 0.7, 11.6 ± 0.7, 17.5 ± 1.0 mm Hg/min (p < .0001) and 23.4 ± 1.0, 19.5 ± 1.8, 16.9 ± 1.8 mm Hg (p = .03) with each of the different ventilation rates, respectively (p = comparison of 12 breaths/min vs. 30 breaths/min for mean intratracheal pressure and coronary perfusion pressure). Survival rates were six of seven, one of seven, and one of seven with 12, 30, and 30 + Co2 breaths/min, respectively (p = .006). Conclusions:Despite seemingly adequate training, professional rescuers consistently hyperventilated patients during out-of-hospital CPR. Subsequent hemodynamic and survival studies in pigs demonstrated that excessive ventilation rates significantly decreased coronary perfusion pressures and survival rates, despite supplemental Co2 to prevent hypocapnia. This translational research initiative demonstrates an inversely proportional relationship between mean intratracheal pressure and coronary perfusion pressure during CPR. Additional education of CPR providers is urgently needed to reduce these newly identified and deadly consequences of hyperventilation during CPR. These findings also have significant implications for interpretation and design of resuscitation research, CPR guidelines, education, the development of biomedical devices, emergency medical services quality assurance, and clinical practice.

Curative percutaneous catheter ablation using radiofrequency energy for accessory pathways in all locations: Results in 100 consecutive patients

Patients with accessory pathway-mediated supraventricular tachycardia have typically been treated with drugs or surgery. Although catheter ablation using high voltage direct current shocks has been used to treat patients with drug-refractory supraventricular tachycardia, there are associated disadvantages, including damage due to barotrauma as well as the need for general anesthesia. Recently, transcatheter radiofrequency energy has evolved as an alternative to direct current shock or surgery to ablate accessory pathways. Percutaneous catheter ablation of 109 accessory pathways with use of radiofrequency energy was attempted in 100 consecutive patients. Patient age ranged from 3 to 67 years. The patients had been treated for recurrent tachycardia with a mean of 2.7 +/- 0.2 antiarrhythmic agents that either proved ineffective or caused unacceptable side effects. In seven patients previous attempts at accessory pathway ablation with use of direct current shock had been unsuccessful. Forty-five (41%) of the pathways were left free wall, 43 (40%) were septal and 21 (19%) were right free wall. Eighty-nine (89%) of the 100 patients had successful radiofrequency ablation at the time of hospital discharge. In all but 12 patients the ablation was accomplished in a single session. Complications attributable to the procedure, but not to the ablation itself, occurred in four patients (4%). No patient developed atrioventricular block or other cardiac arrhythmias. Over a mean follow-up period of 10 months, nine patients had some return of accessory pathway conduction; a repeat ablation procedure was successful in all five patients in whom it was attempted. It is concluded that a catheter ablation procedure using radiofrequency energy can be performed on accessory pathways in all locations. The procedure is effective and safer, less costly and more convenient than cardiac surgery and can be considered as an alternative to lifelong medical therapy in any patient with symptomatic accessory pathway-mediated tachycardia.

Vasopressin Improves Vital Organ Blood Flow During Closed-Chest Cardiopulmonary Resuscitation in Pigs

BACKGROUND This study was designed to compare the effects of epinephrine with those of vasopressin on vital organ blood flow during closed-chest cardiopulmonary resuscitation (CPR) in a pig model of ventricular fibrillation. METHODS AND RESULTS Vasopressin was compared with epinephrine by randomly allocating 28 pigs to receive either 0.2 mg/kg epinephrine (n = 7), 0.2 U/kg vasopressin (low dose) (n = 7), 0.4 U/kg vasopressin (medium dose) (n = 7), or 0.8 U/kg vasopressin (high dose) (n = 7) after 4 minutes of ventricular fibrillation and 3 minutes of closed-chest CPR. Left ventricular myocardial blood flow, determined by use of radiolabeled microspheres during CPR, before and then 90 seconds and 5 minutes after drug administration was 17 +/- 2, 43 +/- 5, and 22 +/- 3 mL.min-1.100 g-1 (mean +/- SEM) in the epinephrine group; 18 +/- 2, 50 +/- 6, and 29 +/- 3 mL.min-1.100 g-1 in the low-dose vasopressin group; 17 +/- 3, 52 +/- 8, and 52 +/- 6 mL.min-1.100 g-1 in the medium-dose vasopressin group; and 18 +/- 2, 95 +/- 9, and 57 +/- 6 mL.min-1.100 g-1 in the high-dose vasopressin group (P < .001 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin, and P < .01 at 5 minutes between epinephrine and medium-dose vasopressin). At the same times, calculated coronary systolic perfusion pressures were 12 +/- 2, 36 +/- 5, and 18 +/- 2 mm Hg in the epinephrine group; 10 +/- 1, 39 +/- 6, and 26 +/- 5 mm Hg in the low-dose vasopressin group; 11 +/- 2, 49 +/- 6, and 38 +/- 5 mm Hg in the medium-dose vasopressin group; and 10 +/- 2, 70 +/- 5, and 47 +/- 6 mm Hg in the high-dose vasopressin group (P < .01 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin); and calculated coronary diastolic perfusion pressures were 15 +/- 2, 24 +/- 2, and 19 +/- 2 mm Hg in the epinephrine group; 13 +/- 1, 25 +/- 2, and 20 +/- 1 mm Hg in the low-dose vasopressin group; 13 +/- 2, 25 +/- 2, and 21 +/- 2 mm Hg in the medium-dose vasopressin group; and 13 +/- 2, 35 +/- 3, and 24 +/- 2 mm Hg in the high-dose vasopressin group (P < .05 at 90 seconds between epinephrine and high-dose vasopressin). Total cerebral blood flow was significantly higher after high-dose vasopressin than after epinephrine (P < .05 at 90 seconds and P < .01 at 5 minutes between groups). Five animals in the epinephrine, 5 in the low-dose vasopressin, 7 in the medium-dose vasopressin, and 6 in the high-dose vasopressin groups were successfully resuscitated and survived the 1-hour observation period. CONCLUSIONS We conclude that administration of vasopressin leads to a significantly higher coronary perfusion pressure and myocardial blood flow than epinephrine during closed-chest CPR in a pig model of ventricular fibrillation.

Regional Systems of Care for Out-of-Hospital Cardiac Arrest. A Policy Statement From the American Heart Association

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.

Vasopressin administration in refractory cardiac arrest

In studies done in pigs, the administration of exogenous vasopressin during closed- and open-chest cardiopulmonary resuscitation has been shown to be more effective than optimal doses of epinephrine in improving vital organ blood flow and increasing perfusion pressure [1, 2]. Interest in the potential value of vasopressin administration during cardiopulmonary resuscitation also stems from human studies showing high levels of circulating vasopressin in patients in cardiac arrest [3, 4]. Higher levels of endogenous vasopressin are associated with greater chances for survival, and higher endogenous levels of epinephrine and norepinephrine are associated with decreased chances for survival [4]. To date, no case reports or controlled studies have addressed the potential value of exogenous vasopressin for the treatment of patients having cardiac arrest. In light of the data from the animal studies, eight patients having refractory in-hospital cardiac arrest were treated with vasopressin after standard therapies, including intravenous administration of epinephrine, had failed. Methods In a final effort to resuscitate patients in whom standard American Heart Association Advanced Cardiac Life Support therapies after in-hospital cardiac arrest had failed, arginine vasopressin was administered centrally as an initial 40-U bolus. Each patient had received standard manual cardiopulmonary resuscitation with at least 1 mg of epinephrine and an attempt at direct-current shock before receiving vasopressin through either a femoral or jugular vein. Table 1 lists patient demographic characteristics, and Table 2 provides some details of therapy and outcome after cardiac arrest. One of eight patients (patient 2) had an unwitnessed arrest. Cardiopulmonary resuscitation was initiated less than 1 minute after arrest in the remaining patients; cardiopulmonary resuscitation and advanced cardiac life support were done on all patients for at least 12 minutes (mean SD, 21.6 11.8 minutes) before vasopressin was administered. Three patients were discharged from the hospital with good neurologic recovery. Table 1. Demographic Characteristics of Patients Having In-Hospital Cardiac Arrest Refractory to Epinephrine*. Table 2. Time Intervals and Outcome in Patients Having In-Hospital Cardiac Arrest Refractory to Epinephrine*. Case Highlights Patient 4 Four days after having a hemicolectomy, a 78-year-old woman developed pulmonary emboli and ventricular fibrillation. Defibrillation (200 J) led to asystole. The patient received cardiopulmonary resuscitation and epinephrine (1-mg, 3-mg, and 5-mg doses administered 3 minutes apart). After the 5-mg bolus, ventricular fibrillation evolved but was resistant to repeated direct-current shocks and to lidocaine (100 mg). Central administration of vasopressin (40 U) followed by direct-current shock (360 J) resulted in a supraventricular rhythm with a palpable carotid pulse. A systolic blood pressure of approximately 100 mm Hg was maintained with a norepinephrine infusion of 0.15 g/kg of body weight per minute. After uncomplicated embolectomy, the patient was transferred to the intensive care unit for 3 days and was discharged without neurologic deficit 4 weeks later. Patient 5 A 71-year-old woman developed ventricular fibrillation while her chest was being scrubbed before implantation of a permanent pacemaker. Closed-chest cardiac massage was initiated within seconds. After three successive direct-current shocks (200 J, 300 J, and 300 J) followed by epinephrine (1 mg) and another direct-current shock (300 J), the patient remained in ventricular fibrillation. Examination of arterial blood gases showed a pH of 7.33 and a Po 2 of 60 mm Hg before endotracheal intubation. Additional epinephrine (1 mg) and defibrillation efforts were unsuccessful. Vasopressin (40 U) was administered 50 minutes after the arrest, and spontaneous circulation returned immediately after a 300-J direct-current shock. Immediately before vasopressin administration, the patients arterial blood had a pH of 7.18 and a Po 2 of 543 mm Hg. The patient was treated with dopamine (10 g/kg per minute) intravenously. Forty-five minutes later, she again developed hypotension followed by ventricular fibrillation. Cardiopulmonary resuscitation was reinitiated, but direct-current shock (300 J), epinephrine (1 mg), and another direct-current shock (300 J) failed to revive her. Vasopressin (20 U) followed 30 seconds later by direct-current shock (300 J) was unsuccessful; more vasopressin (20 U) was administered 2 minutes after the first 20-U dose. Thirty seconds later, a direct-current shock (300 J) led to an immediate return of spontaneous circulation. The patients pulmonary capillary wedge pressure at this time was 25 mm Hg, and her pulmonary systolic pressure was 35 mm Hg. Twenty minutes after her second and final resuscitation effort, she became hypotensive and bradycardic and died secondary to pulseless electrical activity. Patient 6 Immediately after induction with a standard cardiac general anesthetic for placement of an implantable cardioverter-defibrillator, a 45-year-old man developed pulseless electrical activity. Standard closed-chest manual cardiopulmonary resuscitation was started immediately. The patient received fluids (500 mL of normal saline), atropine (1 mg intravenously), and epinephrine (1 mg intravenously). After 10 minutes and another 1-mg epinephrine dose, he developed ventricular fibrillation. Several efforts to defibrillate failed. Twenty minutes after cardiac arrest, the patient received vasopressin (40 U); after a single 360-J transthoracic direct-current shock, spontaneous circulation promptly returned. The patient remained hemodynamically stable for 30 minutes. Despite intravenous fluids, dopamine (10 g/kg per minute), and placement of an intra-aortic balloon pump, he again developed hypotension, followed by ventricular fibrillation. After an effort to resuscitate the patient with standard cardiopulmonary resuscitation, epinephrine (1 mg), and direct-current shock was unsuccessful, the patient was given vasopressin (40 U) and was successfully resuscitated with direct-current shock. An angiogram showed a large thrombus at the site of an angioplasty done 2 weeks earlier; the vessel was again dilated. Within 30 minutes, the patient developed polymorphous ventricular tachycardia and had another cardiac arrest. Standard manual cardiopulmonary resuscitation, intravenous vasopressin (40 U), and direct-current shock were not effective. The patient received active compression-decompression cardiopulmonary resuscitation and vasopressin (40 U). Systolic arterial pressure increased to more than 100 mm Hg; when active compression-decompression cardiopulmonary resuscitation was stopped, the patient spontaneously convertedwithout direct-current shockto sinus tachycardia. One hour later, ventricular fibrillation again developed. Resuscitation efforts were terminated. Patient 8 A 31-year-old man had several internal injuries after a car accident. He developed ventricular fibrillation on the way to the operating room for emergent repair of a ruptured aorta. Fibrillation persisted despite many direct-current shocks and the administration of epinephrine (2 1 mg repeated after 3 minutes). After 4 minutes of closed-chest cardiopulmonary resuscitation, examination of the arterial blood showed a pH of 7.16, a Pco 2 of 54 mm Hg, a Po 2 of 49 mm Hg (fraction of inspired oxygen, 1.0), a potassium level of 2.8 mmol/L, and a hemoglobin level of 9.1 g/L. Despite treatment with epinephrine, diastolic arterial pressures remained less than 15 mm Hg. Administration of vasopressin (40 U) increased the diastolic arterial pressure to 30 mm Hg, and a subsequent direct-current shock (360 J) restored a stable heart and blood pressure. After the operation, the patient was transferred to the intensive care unit. Discussion These cases show that in patients in cardiac arrest who are receiving closed-chest cardiopulmonary resuscitation and have not responded to the standard doses of epinephrine recommended by the American Heart Association, spontaneous circulation can be restored by intravenous administration (through the femoral or jugular vein) of 40 U of vasopressin. These results are consistent with recent data from animals showing that vasopressin has greater efficacy than epinephrine during cardiopulmonary resuscitation [1, 2]. Although the prognosis was poor in all cases and all conventional measures had failed, spontaneous circulation was restored in all eight patients after vasopressin administration. Three patients survived to hospital discharge with minimal or no neurologic deficit. In addition, when active compression-decompression cardiopulmonary resuscitation was combined with the use of vasopressin, one patient had spontaneous conversion to sinus rhythm without the use of direct-current shock. Although the optimal dose of vasopressin in humans is not known, 40 U was effective in all of our patients. In one patient, a dose of 20 U was not effective. In the eight patients studied, an initial dose of 1 mg of epinephrine was administered. In four of these eight patients, an escalating dose of epinephrine (from 1 mg to 3 mg to 5 mg) was used but was similarly ineffective. In humans having cardiac arrest, epinephrine therapy is used on the basis of case reports and animal studies [5, 6]. Recent clinical trials comparing low-dose with high-dose epinephrine show that the latter has no significant advantage [7, 8]. A more recent placebo-controlled trial showed that neither high- nor low-dose epinephrine had benefit compared with placebo [9]. In our patients, vasopressin may have been more effective because of several factors. Vasopressin exerts a greater vasoconstrictive effect under conditions of hypoxia and acidosis than does epinephrine, and the effects of vasopressin last longer [1, 2]. Vasopressin causes a greater increase in arterial tone than does epine

A comparison of standard cardiopulmonary resuscitation and active compression- decompression resuscitation for out-of-hospital cardiac arrest

Background We previously observed that short-term survival after out-of-hospital cardiac arrest was greater with active compression–decompression cardiopulmonary resuscitation (CPR) than with standard CPR. In the current study, we assessed the effects of the active compression–decompression method on one-year survival. Methods Patients who had cardiac arrest in the Paris metropolitan area or in Thionville, France, more than 80 percent of whom had asystole, were assigned to receive either standard CPR (377 patients) or active compression–decompression CPR (373 patients) according to whether their arrest occurred on an even or odd day of the month, respectively. The primary end point was survival at one year. The rate of survival to hospital discharge without neurologic impairment and the neurologic outcome were secondary end points. Results Both the rate of hospital discharge without neurologic impairment (6 percent vs. 2 percent, P=0.01) and the one-year survival rate (5 percent vs. 2 percent, P=0.03) wer...

Comparison of Standard Cardiopulmonary Resuscitation Versus the Combination of Active Compression-Decompression Cardiopulmonary Resuscitation and an Inspiratory Impedance Threshold Device for Out-of-Hospital Cardiac Arrest

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.