Secondary Logo

Journal Logo

The Open Mind: The Open Mind

Ventilation Is an Important Confounding Variable When End-Tidal Carbon Dioxide Is Used to Help Guide Cardiopulmonary Resuscitation

Leinonen, Maria MD; Gravenstein, Nikolaus MD; Giordano, Christopher MD

Author Information
doi: 10.1213/ANE.0000000000004409
  • Free


AHA = American Heart Association; CI = confidence interval; CO2 = carbon dioxide; CPR = cardiopulmonary resuscitation; Etco2 = end-tidal carbon dioxide; PEEP = positive end-expiratory pressure; ROSC = return of spontaneous circulation

The American Heart Association (AHA) further refined cardiopulmonary resuscitation (CPR) in the 2015 AHA CPR and emergency cardiac care guidelines by recognizing end-tidal carbon dioxide (Etco2) as an important adjuvant for prognosticating the outcome of CPR.1 The 2015 guidelines state: “In intubated patients, failure to achieve an Etco2 of greater than 10 mm Hg by waveform capnography after 20 [min] of CPR may be considered as one component of a multimodal approach to decide when to end resuscitation efforts, but should not be used in isolation.”1 We applaud the recommendation but caution about strict Etco2 interpretation in the setting of CPR.


Resuscitation measures are aimed at maximizing perfusion to the heart and brain.2,3 Even at its best, CPR creates very subphysiological cardiac output. Because direct measurements of cardiac output during CPR are not available, other measurements including arterial blood pressure, central venous oxygen saturation, and quantitative waveform capnography have been advanced as clinical surrogates of cardiac output.4,5 They can serve as sensitive indicators of return of spontaneous circulation (ROSC) and can be monitored continuously without interrupting CPR.1

Clinical studies show a direct relationship between Etco2 values and cardiac output produced by chest compressions.6,7 Mean Etco2 levels <3 mm Hg immediately after cardiac arrest increase to >7 mm Hg with initiation of chest compressions. Mean Etco2 spikes to >28 mm Hg within 30 seconds of ROSC. A sudden increase in Etco2 (absent an injection of sodium bicarbonate) is typically the earliest clinical indicator of ROSC.8,9 This often occurs before the return of a palpable pulse. A rise in Etco2 by ≥10 mm Hg has an 83% (95% confidence interval [CI], 62%–95%) positive predictive value for ROSC.10 Based on these findings, monitoring Etco2 virtually eliminates the need to stop chest compressions to check for pulses. Several unblinded, design-limited, observational studies have reported that an Etco2 ≤10 mm Hg could accurately predict a nonsurvivable injury in patients receiving appropriate CPR.11,12 One recurring major study limitation is the unmeasured minute ventilation during CPR.


The Etco2 is the consequence of carbon dioxide (CO2) production, transport, and elimination. When 2 of these determinants of Etco2 are held constant, a change in Etco2 reflects a change in the third. During an isolated perfusion problem, as evident during CPR with a fixed minute ventilation, pulmonary blood flow becomes the determinant of alveolar CO2 delivery and thus Etco2. Assuming normal gas exchange, pulmonary blood flow serves as a proxy for cardiac output. A low Etco2 level reflects a low cardiac output if other variables are fixed and normal. These variables are often not fixed, and a low Etco2 can also be a reflection of an airway leak, hyperventilation, pulmonary embolus, hypotension, and cardiac arrest.

Animal and human studies demonstrate a linear relationship between Etco2 and cardiac output. One study showed that, in abdominal aortic aneurysm repair patients with constant minute ventilation, a linear relationship exists between percent changes in Etco2 and percent changes in cardiac output.13 This linear relationship holds true within a wide range of cardiac outputs, including values <25% of normal, which are in the range expected during human CPR. The direct relationship between Etco2 and cardiac output in low-flow states requires a constant minute ventilation.14

During states of low blood flow, alterations in minute ventilation will significantly influence Etco2 values just like changes in cardiac output will. In a multicenter cohort study of 583 cardiac arrests, Etco2 was lowered by an average of 3.0 mm Hg (P < .001) for every 10 breaths/min increase in ventilation rate.15 A report of anesthetized patients observed relatively small changes in minute volume correlate with large changes in Etco2.16 As the cardiac output was not fixed or quantified in the human studies, a linear relationship between Etco2 and minute ventilation has not been definitively established; however, it is clear that the Etco2 value is sensitive to changes in minute ventilation during states of low cardiac output.

Despite the attractiveness of capnography, there are limitations during CPR because Etco2 becomes difficult to interpret with dynamically changing ventilation and circulation. As an example, hypoventilation will elevate the Etco2, but a simultaneous decrease in cardiac output will decrease pulmonary perfusion, and thus bidirectional changes can result in an unchanged Etco2. Even in the ideal scenario with a patient experiencing an isolated circulatory problem, minute ventilation is difficult to precisely control without using a mechanical ventilator. Currently, manual ventilation is most commonly used during CPR despite high inter- and intraprovider variability with manual ventilation.17 Most studies only describe respiratory rate because CPR providers generally do not use spirometry. Unsynchronized chest compressions add another level of variability and uncertainty to the delivery of ventilation.


The 2015 AHA CPR and emergency cardiac care guideline recognizing Etco2 as an important adjuvant for prognosticating the outcome of CPR is identified as “weak” based on limited quality and quantity of data.1 Furthermore, the guidelines offer a “weak” recommendation on respiratory rate that only applies to patients with an advanced airway: “After placement of an advanced airway, it may be reasonable for the provider to deliver [one] breath every 6 s (10 breaths/min) while continuous chest compressions are being performed.”1

Perhaps one of the strongest arguments for monitoring minute ventilation during CPR is to prevent hyperventilation. Hyperventilation has been associated with worse survival rates and resuscitation outcomes in the setting of CPR.18,19 Despite awareness of the detrimental effects of hyperventilation and the recommendation to ventilate 10 breaths/min, inappropriately high respiratory rates (>25 breaths/min) are very common during CPR.1 Manual respiratory rate during CPR on intubated patients is more than double the recommended with a median of 21 breaths/min.18 In contrast to data on the respiratory rate effect, there are limited data on the effects of tidal volume during CPR. One should also consider the potential for this unintended manual hyperventilation to prevent adequate time for breath egress and thereby create an auto positive end-expiratory pressure (autoPEEP) phenomenon through breath stacking. The autoPEEP subsequently increases intrathoracic pressure and limits the return of preload, leading to a hypotensive state manifested not only in a decrease in blood pressure but also in a confounding decrease in Etco2. Thus, inadvertent manual hyperventilation can confound the interpretation of a low Etco2 during CPR via either overventilating alone or overinflating the respiratory system and thereby decreasing pulmonary blood flow.

Comparison of mean Etco 2 values among patients in cardiac arrest who received mechanical versus manual ventilation. Etco 2 indicates end-tidal carbon dioxide; ROSC, return of spontaneous circulation. Hartmann SM, Farris RW, Di Gennaro JL, Roberts JS, Journal of Intensive Care Medicine, vol. 30, issue 7, pp. 426–435, copyright © 2015 by The Authors. Reprinted by Permission of SAGE Publications, Inc.2

The effects of uncontrolled manual ventilation in comparison with controlled mechanical ventilation on Etco2 values during CPR were examined in a meta-analysis.2 The analysis found that participants receiving mechanical ventilation had on average 9.42 mm Hg higher (95% CI, 4.45–14.39) Etco2 levels than those receiving manual ventilation, which is by itself a large enough Etco2 to alter a survivability assessment (Figure).2,18 A confounding consideration then becomes a potentially higher Etco2 value associated with failure to effect ROSC when CPR is done under conditions of mechanical ventilation.


Capnography is a valuable tool during CPR for confirming endotracheal tube placement and detecting ROSC, and it can provide information about the quality of CPR.1 However, when ventilation and circulation are inconstant as during CPR, it becomes difficult to determine the contribution of each to the observed Etco2 level and reach reliable conclusions about the quality of CPR.2,9 Absent conditions of a steady minute ventilation Etco2, interpretations during CPR should be made with caution because the AHA guidelines and clinical evidence leave unanswered questions. If the decision to terminate CPR includes not having achieved an Etco2 of 10 mm Hg (under conditions of manual ventilation), one must also consider if the failure to achieve at least the 10 mm Hg target Etco2 might be as much, or more, of a reflection of hyperventilation than low pulmonary blood flow/cardiac output.20


Name: Maria Leinonen, MD.

Contribution: This author helped research, write, and edit the manuscript.

Name: Nikolaus Gravenstein, MD.

Contribution: This author helped research, write, and edit the manuscript.

Name: Christopher Giordano, MD.

Contribution: This author helped research, write, and edit the manuscript.

This manuscript was handled by: Richard C. Prielipp, MD, MBA.


1. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult advanced cardiovascular life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132:S444–S464.
2. Hartmann SM, Farris RW, Di Gennaro JL, Roberts JS. Systematic review and meta-analysis of end-tidal carbon dioxide values associated with return of spontaneous circulation during cardiopulmonary resuscitation. J Intensive Care Med. 2015;30:426–435.
3. Sutton RM, French B, Meaney PA, et al.; American Heart Association’s Get With The Guidelines–Resuscitation Investigators. Physiologic monitoring of CPR quality during adult cardiac arrest: a propensity-matched cohort study. Resuscitation. 2016;106:76–82.
4. Meaney PA, Bobrow BJ, Mancini ME, et al. CPR quality summit investigators, the American Heart Association emergency cardiovascular care committee, and the council of cardiopulmonary, critical care, perioperative and resuscitation. cardiopulmonary resuscitation quality: improving cardiac resuscitation outcomes both inside and outside the hospital. A consensus statement from the American Heart Association. Circulation. 2013;134:1–20.
5. Pantazopoulos C, Xanthos T, Pantazopoulos I, Papalois A, Kouskouni E, Iacovidou N. A review of carbon dioxide monitoring during adult cardiopulmonary resuscitation. Heart Lung Circ. 2015;24:1053–1061.
6. Falk JL, Rackow EC, Weil MH. End-tidal carbon dioxide concentration during cardiopulmonary resuscitation. N Engl J Med. 1988;318:607–611.
7. Garnett AR, Ornato JP, Gonzalez ER, Johnson EB. End-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. JAMA. 1987;257:512–515.
8. Sayre MR, Berg MD, Berg RA, et al.; American Heart Association. Highlights of the 2010 American Heart Association guidelines for CPR and ECC. Available at: Accessed July 15, 2019.
9. Krauss B, Silvestri S, Falk JL. Post TW, Walls RM, Torrey SB, Grayzel J. In: Carbon Dioxide Monitoring (Capnography). 2018. Waltham, MA: UpToDate; Available at: Accessed July 15, 2019.
10. Lui CT, Poon KM, Tsui KL. Abrupt rise of end tidal carbon dioxide level was a specific but non-sensitive marker of return of spontaneous circulation in patient with out-of-hospital cardiac arrest. Resuscitation. 2016;104:53–58.
11. Kolar M, Krizmaric M, Klemen P, Grmec S. Partial pressure of end-tidal carbon dioxide successful predicts cardiopulmonary resuscitation in the field: a prospective observational study. Crit Care. 2008;12:R115.
12. Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med. 1997;337:301–306.
13. Shibutani K, Muraoka M, Shirasaki S, Kubal K, Sanchala VT, Gupte P. Do changes in end-tidal PCO2 quantitatively reflect changes in cardiac output? Anesth Analg. 1994;79:829–833.
14. Kodali BS, Urman RD. Capnography during cardiopulmonary resuscitation: current evidence and future directions. J Emerg Trauma Shock. 2014;7:332–340.
15. Sheak KR, Wiebe DJ, Leary M, et al. Quantitative relationship between end-tidal carbon dioxide and CPR quality during both in-hospital and out-of-hospital cardiac arrest. Resuscitation. 2015;89:149–154.
16. Voscopoulos C, MacNabb CM, George EE. The relationship between minute ventilation and end tidal CO2 in intubated and spontaneously breathing patients. Paper presented at: American Society of Anesthesiologists Annual Meeting; October 12, 2014; New Orleans, LA. Abstract 2282. Available at:;jsessionid=320640512B95CB587A01B0FB8CA7AADF?year=2014&index=8&absnum=4461. Accessed July 15, 2019.
17. Abella BS, Alvarado JP, Myklebust H, et al. Quality of cardiopulmonary resuscitation during in-hospital cardiac arrest. JAMA. 2005;293:305–310.
18. O’Neill JF, Deakin CD. Do we hyperventilate cardiac arrest patients? Resuscitation. 2007;73:82–85.
19. Yannopoulos D, Tang W, Roussos C, Aufderheide TP, Idris AH, Lurie KG. Reducing ventilation frequency during cardiopulmonary resuscitation in a porcine model of cardiac arrest. Respir Care. 2005;50:628–635.
20. Touma O, Davies M. The prognostic value of end tidal carbon dioxide during cardiac arrest: a systematic review. Resuscitation. 2013;84:1470–1479.
Copyright © 2019 International Anesthesia Research Society