Optimizing Ventilation to Improve Survival From Out-of-hospital Cardiac Arrest: the OPTIVO Randomized Controlled Trial

Overview

When the heart stops pumping during cardiac arrest, cardiopulmonary resuscitation (CPR) is used to continue pushing blood and providing oxygen to vital organs. CPR involves a combination of chest compressions (to push the blood) and ventilations (to provide oxygen and gas exchange). There is a lot of research that has helped to optimize the provision of chest compressions, however there is considerably less research available to guide ventilations. The current guideline recommendations are based on limited data, and no data that is specific to cardiac arrest patients. There is a recognized need for research to better guide ventilation during CPR. This research will help to better define appropriate ventilation targets for cardiac arrest patients.

Rationale Chest compressions and ventilations are the two primary components of cardiopulmonary resuscitation (CPR); one of the few treatments to get a Class 1 recommendation from the American Heart Association (AHA) guidelines for the treatment of patients in cardiac arrest. While there is a significant body of literature examining chest compression quality the evidence regarding optimal ventilation quality is limited. Current guidelines recommend providing ventilations of 500-600ml, or enough for chest rise, to adult patients in cardiac arrest in either a 30:2 ventilation to chest compression ratio without an advanced airway or one breath every six seconds (10 per minute) with an advanced airway. Little has changed in these recommendations over the last 10 years. It is recognized, however, that the evidence informing these recommendations is based on limited, low-quality evidence from non-cardiac arrest populations. Both the International Liaison Committee on Resuscitation (ILCOR) and the AHA have identified that there remains a significant knowledge gap with respect to optimal ventilation strategies during out-of-hospital cardiac arrest (OHCA) resuscitation. Hyperventilation and Hypoventilation Proper ventilation during cardiac arrest is important to provide oxygenation to vital organs, such as the brain, and remove harmful metabolism by-products (e.g. carbon dioxide). Improper ventilation, both hypoventilation (too little) and hyperventilation (too much) can be detrimental to patient survival and neurological outcomes. What constitutes optimal ventilation, however, is unknown. Hypoventilation can lead to increased ischemic injury from reduced oxygen delivery to the brain during cardiac arrest. It can also cause a build-up of CO2 resulting in a respiratory acidosis which can have detrimental consequences to the heart and cardiovascular function. The amount of ventilation that is required during cardiac arrest though is not known. Research examining passive oxygenation (no active ventilation) demonstrates mixed results with respect to cardiac arrest outcomes. While outcomes have been mixed, in general passive oxygenation may not provide sufficient tidal volumes (often under 20mL) generated with chest compressions for adequate gas exchange. Hyperventilation can lead to air-trapping and an increase in intrathoracic pressure, leading to increased right atrial pressure, decreased coronary perfusion pressure, and decreased venous return and cardiac output.9 During positive pressure ventilation, the increase in intrathoracic pressure during inspiration leads to a decrease in right ventricular preload, ultimately decreasing cardiac output. Decreased cardiac output and coronary perfusion lead to reduced rates of return of spontaneous circulation, which ultimately leads to reduced survival. Aggressive ventilations can also cause gastric insufflation and gastric regurgitation leading to pneumonia and other associated airway complications. Previous research has shown that ventilation with lower volumes (365mL) is associated with lower airway pressures, and reduced incidence of gastric insufflation without changes in oxygen saturation. Similarly, ventilations with 6mL/kg result in same CO2 clearance as larger tidal volumes. Furthermore, research examining end-tidal CO2 tracings has hypothesized that hyperinflation is a common phenomenon during cardiac arrest. Performance of Ventilation During Cardiac Arrest Proper ventilations during cardiac resuscitation are challenging to perform. Chang et al. (2019) found that lung inflation occurred infrequently during pauses in chest compressions, however, that an increased number of ventilations were associated with increased rates of ROSC and survival to hospital discharge. Vissers et al. (2019) found no correlation between ventilation rate and ROSC, however found that hyperventilation was common, occurring in 85% of resuscitations. Variability in patient characteristics and logistical challenges, such as limited physical space, make it difficult to perform consistent high-quality ventilations. While AHA guideline indicate 500 to 600mL of volume per ventilation, recognition of chest rise often occurs at volumes that are significantly lower. This creates a conflict within the AHA recommendation on the appropriate volume of ventilation. Chest rise has been shown to occur at volumes 362 to 402mL with an average of 384mL. Previous Literature There is a paucity of high-quality evidence to support current ventilation guideline recommendations, and the available evidence lacks patient-oriented outcomes such as survival to hospital discharge, or neurological outcome. Evidence for ventilations during cardiac arrest is mostly borrowed from animal research or anesthesiology literature indicating that ventilations of 6 to 8 ml/kg of ideal body weight is sufficient in patients in respiratory arrest and is enough volume to create visible chest rise. This volume has not been demonstrated to be sufficient, nor ideal in the cardiac arrest population. It is known that cardiac output is approximately 30% of normal during chest compressions and therefore ventilation requirements may also be different. Previous research has found that passive insufflation is as effective as positive pressure ventilation, at least during the first few minutes of witnessed cardiac arrest resuscitation which begs the question of how much ventilation is required. Other research examining ventilation quality has found decreased survival associated with hyperventilation. A small observational study by Sutton et al. (2019) found a decrease in survival and neurological outcome in paediatric patients with both low and high ventilation rates. They also identified that the 'sweet spot' for ventilation rate, that was associated with the highest survival and neurological outcome, was higher than recommended by the AHA guidelines. One significant barrier to optimizing ventilations during OHCA has been the inability to accurately measure the quality of ventilations being performed by paramedics in the field. Until recently there has been no method available in the prehospital setting to provide accurate, real-time measurement and feedback of ventilation rate and/or volume. Utilization of feedback devices has been shown to improve the quality of chest compressions performed in the field. Similarly the use of tidal volume feedback devices has been shown to improve the proportion of ventilations within target range during simulated cardiac arrest resuscitation. A simulation study using the ZOLL Accuvent® ventilation monitor found that ventilations significantly improved with the use of real-time feedback during simulated cardiac arrests. The authors found that the use of real-time feedback resulted in a increase in target compliance for ventilation rate from 41% to 71%, ventilation volume from 31% to 79% and for rate and volume together from 10% to 63%. Similarly, Lyngby et al. (2021) performed a randomized controlled trial with 64 paramedics using simulated cardiac arrest scenarios. They found that use of real-time feedback was able to significantly improve guideline compliance in terms of ventilation rate and volume as combined or individual parameters. Charlton et al. (2021) found similar results in 106 paramedics when performing 2-minute simulated scenarios. Our previous publication is the only published literature examining ventilation during cardiac arrest with ventilation feedback devices. We identified that without feedback, ventilations rarely meet guideline recommendations, however compliance significantly improved with ventilation feedback. The average ventilation volume was much lower than guideline targets (395mL). Significance of the project This study will constitute the most rigorous evaluation of the impact of ventilations during cardiac arrest on patient outcomes. This is an area of research that is of huge importance but is significantly under studied as until recently it was not possible to reliably measure ventilation quality in the field. There are significant knowledge gaps in our understanding of the importance of ventilations during resuscitation and what are the key indicators of ventilation quality. Multiple simulation studies have indicated that use of real-time feedback significantly improves the quality of ventilations performed by paramedics, however none of these studies were on real patients, performed in the field, or had any patient-oriented outcomes associated with them. This study will build upon previous simulation studies to examine real-time feedback in the field during actual cardiac arrests and examine the association of ventilations with patient outcomes. The results of this study will have guideline informing implications, leading to improvements in clinical practice. These improvements in care could lead to increased survival from out-of-hospital cardiac arrest. Further, this research will lead to other important questions regarding the relationship between ventilations, cardiac arrest care, prognostication and patient outcomes.