Cardiac arrest remains a leading cause of mortality worldwide, emphasizing the critical need for effective resuscitation techniques. Recent advancements in ventilation technology have the potential to play a pivotal role in improving patient outcomes from cardiac arrest. Understanding the nuances of ventilation while striking a balance between providing adequate support and avoiding complications is essential yet remains elusive.

During cardiac arrest, effective ventilation is important for maintaining oxygen delivery to vital organs, particularly the heart and brain. Proper positive pressure ventilation supports gas exchange, helping to restore normal physiologic function after return of spontaneous circulation (ROSC). The primary goals of ventilation during resuscitation are to ensure adequate oxygenation and facilitate the removal of carbon dioxide ( co ₂ ) without inducing additional injury. There are known consequences of improper ventilation in this vulnerable patient population.

Hyperventilation

Hyperventilation, delivery of large tidal volume (Vt) and/or faster than normal respiratory rate (RR), has a number of potential detrimental effects. High minute ventilation leads to hypocapnia and alkalosis shifting the oxygen-hemoglobin dissociation curve to the left and decreasing oxygen delivery. Excessive stretch, regional lung hyperinflation, and repetitive airway opening play a role in lung injury and place patients at risk for acute respiratory distress syndrome (ARDS). This event, no matter the phase of resuscitation, kicks off a cascade of inflammatory cytokines and other biologic mediators along with hyperoxia that contribute to progressive pulmonary dysfunction, multiple organ failure, and death. ^,

During cardiopulmonary resuscitation (CPR), an increase in intrathoracic pressure created by excessive positive pressure ventilation (ie, hyperventilation) can lead to a decrease in venous return and cardiac output, ^, potentially impacting patient survival. In addition, hyperventilation can mechanically increase pulmonary vascular resistance and injure the lung from excessive pressure (barotrauma), excessive volumes (volutrauma), or poor compliance owing to air trapping from inadequate expiratory times, especially during chest compressions that intermittently obstruct the airways during the passive expiratory phase.

Following ROSC, persistent hyperventilation can lead to subsequent hypocapnia and resultant cerebral vasoconstriction. High intracranial pressure threatens the integrity of the brain and can adversely affect neurologic outcome. Hyperventilation is used to decrease intracranial pressure by reducing cerebral blood flow and volume. Hyperventilation in patients with traumatic brain injury can result in a 34% decrease in cerebral blood flow and 9% decrease in cerebral blood volume.

Hypocapnia induced by hyperventilation increases cerebral neuronal excitability and seizure duration, increasing oxygenation and glucose consumption, excitatory amino acid production, and anaerobic metabolism. ^, Hyperventilation creates a reduction in oxygen supply and delivery, followed by an increase in oxygen consumption that leads to demand outstripping supply and further brain tissue hypoxia ( Fig. 1 ).

Effects of abnormal ventilation. CBF, cerebral blood flow; CBV, cerebral blood volume; CPP, cardiac perfusion pressure; GFR, glomerular filtration rate; HR, heart rate; IP, intracanial pressure; RBF, renal blood flow; SV, stroke volume; VILI, ventilator induced lung injury.

( Created in BioRender. Walsh, B. (2025) https://BioRender.com/pkcfnvp .)

There is a lack of evidence informing the current understanding of ventilation requirements during cardiac arrest. The American Heart Association guidelines recommend for adult patients in cardiac arrest a volume of ventilation sufficient to cause chest rise, or approximately 500 to 600 mL, and a ratio of 30 chest compressions to two ventilations without an advanced airway, or one ventilation every 6 seconds asynchronously during continuous chest compressions with an advanced airway in place. The European Resuscitation Council similarly suggests providing enough volume to see visible chest rise without specifying an estimated volume, while attempting to avoid gastric insufflation. These recommendations are supported by the International Liaison Committee on Resuscitation (ILCOR) Consensus on Science with Treatment Recommendations. ^, There are no data, however, that suggest these are the optimal ventilation parameters during cardiac arrest.

Research has focused on multiple aspects of ventilation during cardiac arrest, including chest compression to ventilation ratio, the role of passive oxygenation, ventilation rate and volume, and differences in ventilation between basic and advanced airway devices. The quality of evidence varies for the different aspects of ventilation. Chest compression to ventilation ratios and asynchronous versus synchronous ventilations remain controversial areas in resuscitation. Over time, resuscitation science has moved to increase the number of chest compressions, reducing the number of ventilations that are administered.

A large, randomized trial found no difference in patient survival between continuous chest compressions and 30:2 compressions to ventilations. Ventilation rate is supported by multiple observational studies. ^, The challenge with all these studies, however, is that none of them were able to measure the actual ventilations delivered. Much of the evidence supporting recommendations for ventilation volume is extrapolated from other areas of medicine, such as anesthesiology and critical care. There is a paucity of research specific to cardiac arrest population. Previous guidelines supported higher ventilation targets, suggesting volumes of 800 to 1200 mL to provide appropriate oxygenation and ventilation during CPR. Subsequent research identified that similar partial pressure of oxygen and partial pressure of carbon dioxide could be obtained with smaller volumes, with less risk of gastric insufflation. Guideline organizations therefore started to recommend smaller volumes of ventilation (500–600 mL). There is no evidence, however, that these volumes are associated with improved patient outcomes.

Current research studies examining ventilation during cardiac arrest suffer from several limitations that make interpretation challenging. Most studies are retrospective in nature and suffer from inherent limitations in study design, including significant risk of confounding. These limitations make it difficult to determine whether patient outcomes are due to differences in ventilation, or some other related factor. In addition, cardiac arrest research, which largely occurs in the out-of-hospital setting, is a challenging setting to conduct research. The uncontrolled and chaotic nature of the out-of-hospital environment adds to the complexity of performing high-quality research to examine the importance of ventilation during cardiac arrest.

Research examining ventilation is highly prone to measurement error, as tools to accurately measure ventilation delivery during manual bag-mask ventilations are limited. It is therefore likely that the ventilations are often not provided as intended. Idris and colleagues found that, during basic life support CPR, 30:2 chest compression to ventilation, when EMS providers paused chest compressions to deliver ventilations, during most pauses, less than two ventilations were actually delivered.

Ventilation research is further confounded by the fact that cardiac arrest is a heterogeneous disease in which patients likely have different ventilation requirements based on the cause of the cardiac arrest (cardiac vs respiratory), patient demographics (age, sex), and underlying comorbidities (pulmonary disease). These challenges have contributed to the limited understanding of proper ventilation during cardiac arrest, and there remains considerable knowledge gaps with respect to optimizing ventilation delivery.

Manual ventilation is a complex and difficult skill to master. Despite best efforts, high-quality manual ventilation is often not achieved in the out-of-hospital or in-hospital setting. This is especially true with bag-mask ventilation, which has the added complexity of requiring a good mask seal to the patient’s face to allow ventilation to occur.

There are several tools and techniques available that can help to ensure effective manual bag-mask ventilation. Oropharyngeal and nasopharyngeal airways can help to alleviate the tongue from the back of the oropharynx and direct air to the trachea. The use of manometers to monitor pressure during ventilation can help to ensure that manual breaths are not delivered with pressures that can lead to alveolar damage or increase the risk of gastric insufflation. Utilization of a two-person bag-mask technique has been shown to be superior compared with single-person ventilation. With two-person bag-mask ventilation, one provider performs the mask seal with the thenar eminences, while the second provider delivers the ventilations in contrast to the standardly taught one-person “E-C clamp” technique. Multiple studies have demonstrated superior ventilations with this two-person technique, ^,, especially with inexperienced providers and those who have a difficult time obtaining an adequate mask seal (eg, smaller hands or difficult patient anatomy).

Utilization of pediatric or small adult bag-mask ventilation has been suggested to limit the volume of ventilation and avoid hyperventilation. A recent study by Snyder and colleagues, however, found that the use of a small adult ventilation bag resulted in lower rates of ROSC than with standard-size adult bag-mask. The effects of minute ventilation, acid base status, and hemodynamics remain unclear and need additional research.

One of the challenges with manual ventilation is that monitoring the quality of ventilations is limited. Beyond visualization of chest rise, there are few tools available to allow for more objective determination of appropriate ventilation. Chest rise on average can be detected with 186 mL of volume and is deemed sufficient at approximately 350 to 400 mL. This is a subjective measurement, dependent on the observer, and varies person to person and with the environment in which ventilation is delivered (eg, floor, moving vehicle, stretcher, and so forth). In addition, it can be difficult to administer adequate volume and to visualize chest rise without pausing chest compressions to deliver ventilations; however, current recommendations are to perform continuous chest compressions after an advanced airway has been placed. Therefore, other methods to monitor ventilation quality are needed.

End-tidal carbon dioxide (ET co ₂ ) monitoring provides valuable information for several aspects of cardiac arrest management but is limited in its ability to guide ventilations. ET co ₂ measurements rely on a complex interaction between metabolism, perfusion, and ventilation. During cardiac arrest, ET co ₂ values reflect cardiac output and deranged metabolism, making it difficult to reliably use ET co ₂ values to guide ventilations. ET co ₂ can, however, be used to count RR as a valuable component of ventilation delivery.

Last, there is a large body of research comparing basic and advanced airway management for delivery of ventilations during cardiac arrest. Overall, the evidence supports either an advanced airway or bag-mask ventilation, as long as the technique used is appropriate for the situation and the provider has adequate training and experience to ensure a high rate of success with limited interruptions in chest compressions. ^,, One limitation of all the randomized trials on airway management is that the quality of ventilations was not measured. This remains a major knowledge gap, and presumably at least as important a question as which device providers should use to deliver those ventilations. Despite the neutral trial findings, there are some nuanced reasons advanced airways may be advantageous that were not evaluated in the clinical trials. First, advanced airways allow for continuous chest compressions, which can improve chest compression fraction, a significant predictor of patient outcomes. In addition, advanced airways provide a continuous seal to help limit insufflation of the stomach, while maintaining a patent airway that will allow for better sampling and lead to more accurate monitoring of ET co ₂ . One of the limitations of advanced airways is that it is difficult to monitor chest rise, currently the recommended indicator of sufficient ventilation. As most resuscitations in Advanced Life Support environments receive an advanced airway at some point during the resuscitation, it is imperative to identify additional means of monitoring ventilation quality.

ET co ₂ measurement provides valuable information and has several indications in the management of cardiac arrest. ET co ₂ remains the gold standard for confirmation of placement of an advanced airway. In addition, ET co ₂ provides valuable information about chest compression quality, the occurrence of ROSC, and prognostication of patient outcomes.

Chest compression quality, most often chest compression depth, has been associated with ET co ₂ values with deeper chest compressions providing increased ET co ₂ values. ^, ET co ₂ values less than 20 mm Hg are often suggested to indicate that chest compressions should be improved during resuscitation. ^,

ET co ₂ values that remain less than 10 mm Hg after 20 minutes of advanced life support resuscitation are associated with poor outcomes. The specificity of this finding, however, does not consistently demonstrate high enough specificity (>99% specificity) to be considered as the sole criteria to terminate resuscitation. Current guidelines recommend using ET co ₂ as part of a multimodal approach to determining futility. Other studies have examined the prognostic indication of different aspects of ET co ₂ , such as the initial value, ^, the last value, the trend over time, or the time spent under or over a specific threshold value. None of these ET co ₂ values have proven superior in terms of patient prognostication, and the optimal use of ET co ₂ is not known. As research evolves, it is clear that there is much that is not understood with respect to the complexity of ET co ₂ and cardiac arrest management.

Despite the valuable information offered from ET co ₂ monitoring during cardiac arrest, the utility of ET co ₂ in monitoring or guiding ventilation quality is not known. Previous research has demonstrated that ventilation rate can impact ET co ₂ measurement with faster rates resulting in lower ET co ₂ readings. ^, However, ET co ₂ measurements are significantly confounded by chest compression quality (perfusion), duration of cardiac arrest, medication administration (epinephrine and sodium bicarbonate), ^,, and underlying patient factors, making it unreliable to use to guide ventilation during cardiac arrest management.

Real-time ventilation feedback devices have recently been developed that may help improve the understanding of the optimal ventilation strategy in cardiac arrest. Currently available devices use pressure-based flow sensors to measure and provide calculated values for different ventilatory parameters, such as inspiratory and expiratory Vt, ventilation rate, and air leak, while providing real-time feedback during resuscitation. Utilization of these devices may provide information for advancement in both clinical practice, through the delivery of real-time feedback, and in future research, as a method of evaluating ventilation delivery during clinical trials. A growing number of studies suggest that real-time ventilation feedback can increase compliance with guideline recommendations for ventilation rate and Vt in simulated settings.

Gould and colleagues performed a before-and-after simulation study using teams of emergency medical technicians. Teams performed two 8-minute rounds of CPR, first without real-time ventilation feedback followed by a round with real-time feedback. The investigators found that ventilation rate and volume compliance with targets were significantly improved (41% vs 71%; P <.01) and (31 vs 79%; P <.01), respectively, with the use of real-time visual feedback. Similarly, subsequent simulation studies have continued to demonstrate improved compliance with ventilation parameter targets with the use of real-time feedback devices. ^,,,,, A recent ILCOR scoping review article identified 13 simulation studies and a single before-and-after clinical study examining the use of real-time ventilation feedback in cardiac arrest management. The findings were consistent across all studies that use of real-time feedback improved ventilation parameters. However, there was a noticeable lack of clinical studies and patient-centered outcomes; thus, no recommendations were made.

Drennan and colleagues conducted a before-and-after study of the implementation of real-time ventilation feedback in the field in 412 cases of cardiac arrest. They found improved compliance with predefined targets for both ventilation volume and rate with the use of real-time feedback. The investigators, however, did not find any statistical relationship between ventilation parameters and ROSC, although the study was likely underpowered to detect a significant finding.

Although the results of early studies show promise, suggesting improved ventilation with real-time feedback, additional research is necessary to determine the utility of feedback devices in clinical practice. Future research should focus on two main areas of ventilation. First, are providers consistently achieving ventilation targets during cardiac arrest management? Second, what is the relationship between ventilation parameters and patient outcomes? Optimization of ventilation targets and ensuring accurate delivery may lead to significantly improved outcomes from cardiac arrest.

Early studies examining real-time ventilation feedback mimic the introduction of real-time chest compression feedback devices. Although chest compression feedback devices have consistently shown improved performance in simulated and training environments, the results in clinical settings have been mixed. Most clinical studies continue to demonstrate improvements in chest compression quality metrics; however, they report inconsistent impacts on clinical outcomes. Interestingly, consistent across most studies, ventilation rate and chest compression rate appear to benefit most from real-time feedback, whereas chest compression depth and ventilation volume appear to be more challenging to improve.

Consistent with the introduction of chest-compression feedback, it is unlikely that implementation of ventilation devices without appropriate training and ongoing quality assurance/improvement programs will be sufficient to improve ventilation quality. Implementation of new technology requires time to adopt the technology and an ongoing cycle of evaluation and feedback. Feedback devices should be implemented as part of a larger program aimed at high-performance resuscitation. In addition, implementation of ventilation feedback involves additional challenges, as little is known about the optimal ventilation requirements for patients during cardiac arrest. Research must now determine whether improved technical compliance translates to better patient outcomes, including ROSC, survival to discharge, and neurologic recovery.

Airway closure, in which there is interrupted communication between the proximal airway opening and distal alveoli, can result in a lack of insufflation of alveoli and a reduction in gas exchange despite manual or mechanical ventilation (MV) efforts. The effect of airway closure has been described in other clinical conditions, such as obesity, asthma, and ARDS, especially in situations with use of low positive end-expiratory pressure (PEEP). This same phenomenon has been described in patients with cardiac arrest after intubation. ^, Physiologically, it is hypothesized that chest compressions result in a reduction in lung volume below the end-expiratory volume, or functional residual capacity, which causes closure of the small distal airways. ^, Airway closure may alter measurements of driving pressure, underestimate lung compliance, and cause alveolar collapse, resulting in lung damage and poor ventilation in patients with cardiac arrest.

Several studies have demonstrated that the presence of airway closure can be detected by capnogram waveform patterns during ET co ₂ monitoring. ^,,,, As discussed previously, chest compressions can impact ET co ₂ interpretation. In some instances, chest compressions cause oscillations in the capnogram waveforms ( Fig. 2 ). ^, This oscillating pattern is what would be expected in an airway without airway closure as air enters and exits the system during decompression and compression of the chest. In other instances, there are no oscillations in the capnogram waveform with chest compressions. This stable capnogram tracing represents airway closure. Nonoscillating patterns (airway closure) have been identified in up to 60% of patients in cardiac arrest. These patterns in capnogram waveforms change over the course of resuscitation, with an increase in nonoscillating patterns (airway closure) occurring later in the resuscitation, suggesting that ventilation may become less effective with longer duration of CPR.

ET co ₂ waveform patterns.

(Lesimple, A., Fritz, C., Hutin, A. et al. A novel capnogram analysis to guide ventilation during cardiopulmonary resuscitation: clinical and experimental observations. Crit Care 26, 287 (2022). https://doi.org/10.1186/s13054-022-04156-0 . )

Furthermore, quantification of the oscillations in ET co ₂ waveforms, termed the airway opening index (AOI), has been described as a ratio of the average change in ET co ₂ owing to chest compressions compared with the maximum ET co ₂ . The AOI is associated with ROSC. Specifically, higher AOI is associated with increased rates of ROSC, presumably because open airways allow adequate oxygen delivery to and co ₂ removal from the alveoli.

One way to reduce the impact of airway closure is through the application of PEEP. The use of PEEP can increase alveolar recruitment and end-expiratory volume, preventing distal airway collapse and improving ventilation. The use of PEEP improves arterial blood gas measurements (pH, P o ₂ , P co ₂ ) in non–cardiac arrest populations at risk of alveolar collapse and in patients in cardiac arrest.

The cardiopulmonary effects of PEEP present a complex balance during low-flow states; thus, the current use of PEEP during CPR remains controversial. PEEP can lead to increased intrathoracic pressure and subsequent reduction in venous return. An animal study reported that PEEP levels exceeding 10 cm H ₂ O can reduce cardiac output by 15% to 25% during CPR.

However, completely avoiding PEEP can lead to alveolar derecruitment, which may increase pulmonary shunt fraction and worsen oxygen delivery. A PEEP value greater than 5 cm H ₂ O is associated with improved oxygenation, although PEEP values between 0 and 5 cm H ₂ O have been associated with optimal oxygen delivery while maintaining cardiac output during CPR.

The potential benefits of PEEP during cardiac arrest resuscitation require investigation, as current recommendations suggest zero to low-pressure PEEP to avoid impaired venous return, but this may lead to airway closure, atelectasis, and impaired gas exchange. Similarly, research should determine optimal fraction of inspired oxygen (FiO ₂ ) settings, as current recommendations suggest 100% oxygen, but the potential for oxidative injury with prolonged exposure to high oxygen concentrations must be balanced against the need for maximal oxygenation during low cardiac output states.

One novel area of evaluation is in using capnogram waveform patterns to guide the use of PEEP and Vt during continuous chest compressions. Lesimple and colleagues identified three patterns of capnogram waveforms: (1) overdistension; (2) regular; (3) airway closure. In a mixed study of bench science and clinical observational research, they calculated a “distention ratio” that was able to separate ET co ₂ waveform patterns into these three groups. Using animal models, they demonstrated that the distention ratio calculated from capnogram waveform patterns of thoracic distention were negatively correlated with mean arterial blood pressure and cerebral perfusion pressure, suggesting that higher distention ratios resulted in impaired circulation during cardiac arrest. The investigators postulated that capnogram patterns could aid in tailoring Vt and PEEP to balance between thoracic distention and airway closure for optimizing ventilation and hemodynamics. Nonoscillating patterns of airway closure indicate potential need to increase PEEP, and oscillating patterns of thoracic distention indicate potential need to decrease Vt.