Assisted Ventilation Does Not Improve Outcome in a Porcine Model of Single-Rescuer Bystander Cardiopulmonary Resuscitation

Most cardiac arrests occur out of hospitals.¹² Bystander CPR substantially improves survival from these out-of-hospital cardiac arrests.^{34567891011121314} However, single-rescuer bystander CPR as recommended by the American Heart Association requires mouth-to-mouth rescue breathing and CC.¹

Unfortunately, mouth-to-mouth rescue breathing creates a barrier to the performance of bystander CPR. In one survey, a majority of American Heart Association–certified BCLS instructors indicated that they would not perform or would hesitate to perform mouth-to-mouth ventilation on most adult strangers.¹⁵ In another study, 45% of physicians and 80% of nurses claimed that they would not perform mouth-to-mouth resuscitation on a stranger.¹⁶ In a third investigation, only 15% of citizens indicated that they would definitely perform CC plus mouth-to-mouth ventilation, even if no one else was available and they were trained in this skill. On the other hand, if no one else was available and CC alone was equally effective, 68% said they would definitely initiate CPR on a stranger.¹⁷ In each of these studies, respondents were primarily concerned about contracting infectious diseases, such as AIDS.

Experimental data suggest that assisted ventilation may not be necessary during CPR in some circumstances.^181920212223 During cardiac arrest, blood flow to the myocardium is the rate-limiting step for oxygen delivery, not ventilation. In addition, passive ventilation during CC and active gasping provide substantial ventilation for brief periods of CPR as long as the airway remains patent.^{18192021222324} However, studies demonstrating comparable 24-hour survival from cardiac arrest after CC with or without assisted ventilation involve relatively short cardiac arrest insults, with nearly 100% survival in both experimental groups.¹⁸²⁰²¹ Moreover, none of these studies evaluated a realistic model of single-rescuer bystander CPR techniques.

In this investigation, we evaluated the need for assisted ventilation during simulated single-rescuer bystander CPR in a swine model of prehospital, witnessed cardiac arrest. We used a VF cardiac arrest interval of 5 minutes (longer than previous survival studies). Standard single-rescuer bystander CPR was simulated for 8 minutes by a sequence of two ventilations with a gas mixture of 17% oxygen and 4% carbon dioxide (consistent with expired air from a rescue breather), followed by 15 CC at the rate of 100 per minute. The other experimental group, which received CC and no assisted ventilation, did not have an endotracheal tube in place during the 8 minutes of simulated bystander CPR. A third group of animals, the control group, received no “bystander” CPR for 13 minutes until the simulated paramedic team arrived. Our hypothesis was that initial treatment of cardiac arrests by CC with or without rescue breathing would result in comparable rates of successful resuscitation, 24-hour survival, and 24-hour good neurological outcome. Our second hypothesis was that CC with or without rescue breathing would result in improved 24-hour survival and neurological outcome compared with a no–bystander CPR control group.

Methods

CPR Model

Swine were used in the present study because they more closely reflect human thoracic and coronary anatomy than do canine preparations.²⁵²⁶²⁷ To simulate bystander-initiated CPR in an out-of-hospital cardiac arrest, we used a 5-minute cardiac arrest VF interval before initiation of BLS, followed by 8 minutes of bystander CPR. A 2- to 5-minute cardiac arrest downtime is common before the performance of basic CPR, during which the bystander recognizes the gravity of the situation and calls for help.⁴⁶ The average paramedic response times for out-of-hospital cardiac arrests range from 4 to 9 minutes in 16 different programs.⁸ In addition, defibrillation after more than 8 to 12 minutes of cardiac arrest is less effective.⁸⁹¹⁰²⁸ Therefore, a prehospital timeline of a 5-minute cardiac arrest downtime, followed by 8 minutes of bystander CPR and then defibrillation, is realistic and potentially life saving. Standard single-rescuer BLS, as per the guidelines of the American Heart Association, included two rescue breaths followed by 15 CC at the rate of 100 per minute, sequentially, until ALS was provided. The rescue breaths were provided with 17% oxygen and 4% carbon dioxide, simulating expired air from a rescue breather.²⁹ This model included a cardiac arrest interval and CPR period that were sufficiently short to permit excellent outcomes in some animals yet sufficiently long to preclude successful resuscitation in many others. These time intervals provided an opportunity to demonstrate that standard and experimental (CC only) CPR procedures were superior to no BLS and allowed a comparison of the two techniques.

Preparation

Experimental protocols were approved by the Institutional Animal Care and Use Committee and followed the guidelines of the American Physiological Society. Experiments were performed on healthy domestic swine weighing ≈20 to 30 kg. After an overnight fast, the pigs were subjected to masked induction of anesthesia with isoflurane followed by oral endotracheal intubation. They were mechanically ventilated with a volume-cycled Harvard ventilator (model 661; Harvard Apparatus, Inc) on a mixture of room air and titrated isoflurane (≈1%). The tidal volume was initially set at 15 mL/kg, and the ventilator rate was set at 16 breaths per minute; ventilator settings were adjusted to maintain end-tidal carbon dioxide at 40±2 mm Hg.

After we obtained a surgical plane of anesthesia, introducer sheaths were placed in the right internal and external jugular veins, left external jugular vein, right carotid artery, and right femoral artery via cutdown technique. Continuous arterial pressure monitoring was performed via a 7F pigtail micromanometer-tipped, solid state catheter (Millar Instruments) placed in the descending aorta near the diaphragm from the right femoral artery. A 5F coronary sinus catheter was placed via the right internal jugular vein. A 7F balloon-tipped flotation catheter was placed in the main pulmonary artery from the left external jugular vein. A 7F pigtail catheter was placed into the left ventricle via the right carotid artery. A 4F bipolar pacing catheter was advanced through an introducer sheath into the right ventricle. After VF was induced, the pacing catheter was removed, and a 5F calibrated micromanometer-tipped catheter (Millar Instruments) was advanced through the introducer into the right atrium. All catheter placement was performed under fluoroscopic guidance.

Measurements

Right atrial and thoracic aortic pressure waveforms, ECG, and end-tidal carbon dioxide levels were continuously monitored and recorded on a four-channel Gould ES 1000 recorder throughout the experiment until the 1-hour simulated ICU period ended. End-tidal carbon dioxide was measured with an infrared capnometer (model 47210A, Hewlett Packard) through a sensor attached to the ventilator circuit at the proximal end of the endotracheal tube. Coronary perfusion pressure during CPR was calculated by subtracting right atrial relaxation (mid-diastolic) pressure from simultaneous aortic relaxation (mid-diastolic) pressure at a single point during three consecutive compression/relaxation cycles. Arterial blood gas specimens were obtained from the thoracic aorta; mixed venous specimens were obtained from the main pulmonary artery; and coronary sinus specimens were obtained via the coronary sinus catheter at baseline (before cardiac arrest) and during CPR (11 minutes after cardiac arrest). Oxygen saturation, Pco₂, Po₂, pH, and hemoglobin levels were measured with a blood gas analyzer (model IL-1306 with model 482 CO-oximeter; Instrumentation Laboratories). Cardiac output and regional blood flow to the left ventricle were determined according to a nonradioactive, colored-microsphere technique^30313233 at baseline (before cardiac arrest) and during CPR (in the interval of 9.5 to 12 minutes after VF). Minute ventilation during the seventh minute of CPR was determined in 3 CC pigs with a heated pneumotachometer (Fleisch size 0; Instrumentation Associates) attached to a well-sealed nose cone mask.

Experimental Protocol

After baseline data were collected, isoflurane was discontinued, and VF was induced by the application of 60-cycle alternating current to the endocardium through the pacing electrode (Fig 1). VF was confirmed by the typical ECG rhythm and precipitous decrease in arterial pressure. Mechanical ventilation was discontinued when VF was noted. A 5-minute VF downtime was followed by an 8-minute BLS period. Animals were randomly assigned into one of three groups: (1) standard CC plus assisted ventilation (CC+V), (2) CC only (CC), and (3) no CPR during the 8-minute BLS period (control group). The CC+V group had endotracheal tubes in place and received two bag-valve-endotracheal tube breaths followed by 15 manual CC at the rate of 100 per minute. This process was repeated sequentially during the 8-minute CPR period. The rescue breaths were provided with a gas mixture of 17% oxygen and 4% carbon dioxide, simulating expired air from a rescue breather. The CC group had the endotracheal tube removed and received 8 minutes of manual CC at the rate of 100 per minute.

At the end of the BLS period (13 minutes after VF was induced), all animals received ACLS according to the American Heart Association algorithms for VF. Electrical shock therapy was provided as if a paramedic group had just arrived, starting with 100 J on the first shock and followed by 200 J on any subsequent defibrillation attempt. CC animals were reintubated during the minute immediately preceding the first defibrillation attempt. If the three initial attempts at defibrillation were unsuccessful, CPR was restarted, and epinephrine (1 mg/kg) was administered intravenously. After epinephrine administration, CPR was continued for 30 seconds to allow circulation of the epinephrine before further attempts to defibrillate. CPR by this simulated “paramedic team” included ventilation with 100% oxygen on a volume-cycled ventilator at a rate of 15 breaths per minute and CC manually at a rate of 100 compressions per minute. Restoration of spontaneous circulation was defined as unassisted pulse with a systolic arterial pressure of ≥50 mm Hg and a pulse pressure of ≥20 mm Hg lasting for ≥1 minute.

Intensive Care

All successfully resuscitated animals were supported aggressively for 1 hour in a simulated ICU setting. Systolic blood pressure was sustained at >80 mm Hg with dopamine and/or volume administration, as clinically indicated. All pigs received 10 mL/kg normal saline IV during the ICU period. Ventricular arrhythmias were treated with lidocaine or electroshock therapy as necessary. Mechanical ventilation was provided with 100% oxygen and adjusted to obtain an end-tidal carbon dioxide of 40±2 mm Hg. Recurrent cardiac arrest was treated with standard CPR and ALS according to the American Heart Association algorithms. At the end of 1 hour, all animals were weaned from pharmacological and ventilatory support. Throughout the ICU period, isoflurane was administered, as necessary, to maintain adequate analgesia and anesthesia. Animals that survived the ICU period were transferred to observation cages for the next 24 hours.

Outcome and Neurological Evaluation

Survival and neurological status were evaluated at 24 hours after the initial cardiac arrest. To provide objective neurological evaluation, Swine Neurological Deficit Scores and Swine Cerebral Performance Categories were assessed.^18203435 Briefly, the neurological deficit score assigns values for deficits in neurological functions, so that a score of 0 is normal and a score of 400 is brain death. Swine Cerebral Performance Category is a more global assessment of neurological function, with category 1 being normal and category 5 being brain death. After the 24-hour evaluation, survivors were killed by an infusion of Euthanol.

Data Analysis

Heart rates and systolic and diastolic aortic and right atrial pressures were collected from the graphic records at prearrest baseline and 15 minutes after resuscitation. Aortic and right atrial compression and relaxation pressures were collected from the graphic records at 6, 8, 10, and 12 minutes after induction of VF. Average left ventricular myocardial blood flow was determined by adding epicardial and endocardial flow values from the anterior, inferior, and lateral walls of the left ventricle and dividing by 6.

Continuous variables, such as blood pressures, coronary perfusion pressures, blood gas analyses, electrical shocks and epinephrine doses during resuscitation, and Swine Neurological Deficit Scores, were evaluated with ANOVA. For all significant variables, differences between group means were evaluated with Scheffé’s test. During BLS, comparisons between the CC+V and CC groups of blood pressures, myocardial perfusion pressures, myocardial oxygen delivery, myocardial oxygen consumption, cardiac outputs, and regional blood flows were evaluated with the use of unpaired Student’s t tests. The Student’s t test was used instead of ANOVA because such data were not obtained in the control group. Continuous variables are described as mean±SEM. Comparisons of discrete variables, such as rate of return of spontaneous circulation, animals receiving dopamine and lidocaine during resuscitation or ICU management, 24-hour survival, and 24-hour neurologically intact survival, were evaluated with the use of Fisher’s exact test.

Results

Twenty-six animals were studied (weight, 25±1 kg). All 10 CC animals, 9 of the 10 CC+V animals, and 4 of the 6 control animals attained return of spontaneous circulation. Five of the 10 CC animals and 6 of the 10 CC+V animals survived for 24 hours, whereas none of the 6 control animals survived for 24 hours. Survival in the CC+V group was statistically superior to that in the control group (P<.03), and survival in the CC group tended to be superior (P=.058). All 24-hour survivors were neurologically normal on the basis of the Swine Cerebral Performance scale (cerebral performance category 1) and normal or nearly normal on the basis of the Swine Neurological Deficit Score (5±5 for CC and 19±12 for CC+V). These 24-hour survivors were walking, drinking, eating, and acting normally.

Baseline weights, hemoglobin concentrations, and hemodynamic data before defibrillation did not differ significantly among the three groups (Table 1). Blood pressures obtained during CPR in the CC+V and CC groups were generally comparable (Table 2), although the CC group had higher coronary perfusion pressures after 1 minute of CPR than did the CC+V group (19.2±3.4 versus 9.5±1.4 mm Hg, P<.05). On the other hand, there were no differences in aortic systolic pressure between the two groups after 1, 3, 5, or 7 minutes of CPR (ie, 6, 8, 10, and 12 minutes of VF), suggesting that the force of compressions was comparable in both groups. Hemodynamic data at 15 minutes after resuscitation did not differ among the three groups.

Difficulty with resuscitation and ICU management was further estimated by comparing the three groups in terms of number of electrical shocks and epinephrine doses during resuscitation and the need for dopamine or lidocaine during resuscitation or ICU management (Table 3). No significant differences were noted, although there was a tendency toward more epinephrine doses in the control group compared with the CC group (P=.06).

Arterial and mixed venous Po₂ and So₂ levels generally did not differ among the three groups at baseline, although the baseline mixed venous So₂ was greater in the CC+V group than in the control group (Table 4). Coronary sinus Po₂ and So₂ levels of the CC and CC+V groups also did not differ at baseline. During CPR, the arterial Po₂ was higher in the CC+V group than in the CC group. The arterial So₂ also tended to be higher in the CC+V group than in the CC group (P=.052). However, the two experimental groups did not differ with respect to mixed venous or coronary sinus Po₂ or So₂ levels during CPR. Both experimental groups had significantly lower mixed venous Po₂ and So₂ levels than the control group during CPR.

Baseline arterial and mixed venous pH and Pco₂ levels were very similar among the three groups (Table 5). Arterial and coronary sinus pH was statistically lower in the CC+V group than in the CC group (7.39±0.01 versus 7.44±0.01, P<.01, and 7.32±0.04 versus 7.40±0.01, P<.05, respectively), but the mean values for the two groups were quite similar and within normal limits. During CPR, arterial pH was higher and Pco₂ was lower in the CC+V group than in the CC group. The mixed venous pH of the two experimental groups was not different, but the control group was significantly less acidotic than either of the experimental groups. In addition, the mixed venous Pco₂ tended to be higher in the CC group than in the CC+V group (P<.06). Coronary sinus specimens taken during CPR were markedly acidotic and hypercarbic in both experimental groups without demonstrable group differences.

Left ventricular myocardial regional blood flows were measured for 10 pigs (5 CC+V and 5 CC), but the results from 2 CC swine could not be evaluated due to technical problems. There were no differences in left ventricular myocardial blood flows between the experimental groups at baseline or during CPR (Table 6). In addition, there were no differences in cardiac output or oxygen delivery between the two groups at baseline or during CPR. Systemic oxygen consumption did not differ at baseline but was higher in the CC group than in the CC+V group during CPR. There were no differences between groups in blood flow to either kidney at baseline or during CPR. Furthermore, left and right kidney blood flows were quite similar at baseline and during CPR.

Fifteen of the 26 animals had active gasping, or agonal respirations, during CPR. Some had only a few agonal breaths; some had five to seven deep gasps per minute. None of these animals gasped before CC. Fig 2 demonstrates the percentage of animals with gasping during each 2-minute interval of CPR. Eight of the 10 CC+V animals, 7 of the 10 CC animals, and none of the control animals gasped. All 11 of the 24-hour survivors gasped versus 4 of the other 9 animals in the two experimental groups (P<.01). After 7 minutes of CPR, the minute ventilation was 1.85±0.99 L/min in 3 CC animals.

Discussion

In this realistic model of prehospital single-rescuer CPR, CC alone was as effective as CC plus assisted ventilation in terms of the important outcome variables: 24-hour survival and neurologically intact survival. The excellent outcomes were consistent with the blood gas, blood flow, spirometric, and oxygen delivery data. Although oxygenation of the arterial blood was superior with assisted ventilation during CPR, mixed venous and coronary sinus oxygenation data and left ventricular blood flow and oxygen delivery data suggest that oxygen delivery was comparable in both experimental groups. Furthermore, either form of “bystander” CPR was superior to no bystander CPR.

In 1993, Berg and colleagues¹⁸ demonstrated that swine in fibrillatory cardiac arrest that had been provided CC only for 9.5 minutes maintained arterial pH 7.33 and an arterial Pco₂ of 48 mm Hg. In 1994, Chandra and colleagues¹⁹ demonstrated maintenance of adequate gas exchange for 4 minutes of CC without assisted ventilation in a canine VF model, with arterial oxygen saturation of >90% and minute ventilation of 5.2 L/min during the fourth minute of CPR. In a paralyzed swine VF model, Idris and coworkers²⁴ noted a minute ventilation of 4.5 L/min during the first minute of CC-only CPR, but this gradually decreased to 1.7 L/min by the 10th minute of CPR.

Evidence of effective ventilation with CC-only CPR in the present study is consistent with these previous studies. The minute ventilation was 1.8 L/min after 7 minutes of CPR. In addition, arterial, mixed venous, and coronary sinus oxygen saturations were similar in the two experimental groups after 11 minutes of cardiac arrest (6 minutes with CPR). Assisted ventilation during CPR resulted in more arterial alkalemia and hypocarbia after 11 minutes of cardiac arrest, but the mixed venous and coronary sinus acid-base status was not statistically different. In summary, gas exchange was substantial during CPR with CC only and resulted in arterial, mixed venous, and coronary sinus blood gases similar to those with assisted ventilation.

While evaluating CC with no assisted ventilation in a swine VF model, Noc and colleagues²³ noted that (1) spontaneous gasping occurred during CC-only CPR, (2) the gasping contributed substantially to minute ventilation during CC-only CPR, and (3) gasping was associated with improved outcome. Clark and coworkers³⁵ similarly observed that agonal respirations occurred in 40% of 445 out-of-hospital cardiac arrests, and these gasping breaths were associated with increased survival. Our data also demonstrated that active gasping commonly occurred during CPR and was associated with better outcome.

Study Limitations

The present study has several limitations. By its very nature, it could not be blinded. Nevertheless, the resuscitation and postresuscitation protocols were standardized and strictly observed. The power of this study was limited by the small number of animals. On the other hand, there are three swine CPR 24-hour outcome studies in which CC with and without assisted ventilation are compared.¹⁸²⁰²¹ Thirty-three of the 37 CC animals (89%) and 30 of the 34 CC+V animals (86%) attained 24-hour neurologically intact survival. The outcome has not differed by more than 1 animal in any of these three previous studies or in the present study. The consistency of these findings despite different experimental protocols is an important counterweight to the argument of inadequate power in each individual experiment.

Another limitation is that both groups received excellent CPR. It is unlikely that excellent compressions and mouth-to-mouth ventilation would be provided by a single rescuer in the field. Blood flow obviously decreases rapidly during pauses for ventilation. In this study, the CC+V animals benefited from mechanical ventilation and optimal airway management with an endotracheal tube. Mouth-to-mouth resuscitation is not as controlled, effective, or safe. Most of these factors would tend to bias the data in favor of the assisted ventilation group.

The most important limitation is the applicability of CPR in this animal model to CPR in humans. Most humans with fibrillatory cardiac arrests do not have normal coronary arteries. In addition, upper airway anatomy of pigs differs from that of humans.

Studies in the 1950s clearly demonstrated that mouth-to-mouth rescue breathing is superior to various chest compression and back compression techniques for ventilating paralyzed, anesthetized adults and children.^{3637383940414243} In particular, upper airway obstruction precluded any ventilation in many of the subjects. These studies form the bases of the A and B of the ABCs of the American Heart Association. On the other hand, recent investigations of the active compression/decompression device (plunger) for CPR in humans have demonstrated that excellent minute ventilation can be attained without assisted ventilation or establishment of an airway.⁴⁴ Although such ventilation may not be reliably attained without adequate airway tone or optimal positioning of the head, the potentially important roles of gasping and airway tone in cardiac arrest victims have not been fully delineated.

An important Belgian study strongly suggests that our findings are applicable to humans.¹³¹⁴ The Belgian cerebral resuscitation group prospectively evaluated 3053 prehospital cardiac arrests. Physicians on the ambulance evaluated the quality and efficiency of bystander CPR. Long-term survival was comparable among those treated with good-quality CC alone (17 of 116, or 15%) and those treated with good-quality CC plus mouth-to-mouth ventilation (71 of 443, or 16%). The outcomes were superior with either of these techniques compared with those receiving no CPR (123 of 2055 survival, or 6%) or good-quality mouth-to-mouth ventilation (2 of 47, or 4%) (P<.001).

Bystander CPR can save lives, but it is usually not offered.^{238111213144546} Single-rescuer CC plus mouth-to-mouth ventilation is a complex psychomotor task that is difficult to learn, teach, remember, and perform.^4748495051 More importantly, bystanders are reluctant to perform mouth-to-mouth ventilation. If CC alone is similarly effective and more acceptable than CC plus mouth-to-mouth ventilation, this simpler technique may result in more lives being saved. The experimental data for this approach are sufficiently strong to justify a randomized, controlled clinical trial.

Selected Abbreviations and Acronyms

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Footnotes