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1 The Journal of Emergency Medicine, Vol. 45, No. 1, pp , 2013 Copyright Ó 2013 Elsevier Inc. Printed in the USA. All rights reserved /$ - see front matter Brief Reports ACCURACY OF END-TIDAL CO 2 CAPNOMETERS IN POST-CARDIAC SURGERY PATIENTS DURING CONTROLLED MECHANICAL VENTILATION Serge J. H. Heines, RN,* Ulrich Strauch, MD,* Paul M. H. J. Roekaerts, PHD,* Bjorn Winkens, PHD, and Dennis C. J. J. Bergmans, PHD* *Department of Intensive Care, Maastricht University Medical Centre, Maastricht, The Netherlands and Department of Methodology and Statistics, Maastricht University, Maastricht, The Netherlands Reprint Address: Serge J. H. Heines, RN, Department of Intensive Care, Maastricht University Medical Centre, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands, Abstract Background: The determination of end-tidal carbon dioxide (etco 2) is very helpful in cardiac resuscitation for confirmation and monitoring of endotracheal tube placement and as an indicator of return of circulation and effectiveness of chest compressions. There is now also widespread use of capnometry on-site at emergency and trauma fields. Objective: We studied the accuracy and correlation of three capnometers (EMMA, Medtronic, and Evita) with partial pressure of arterial CO 2 (PaCO 2 ) measurements. Methods: The three capnometers were placed in-line in the ventilator tubing of the patient. Forty sedated and mechanically ventilated post-cardiac surgery patients were studied. Twenty consecutive etco 2 values were collected simultaneously from all three monitors while drawing an arterial blood sample. Paired sample t-test and Pearson correlation were used to compare the capnometers and their correlation with PaCO 2. Results: The correlation of etco 2 measurements between all three capnometers was good (Emma vs. Evita: 0.874, Emma vs. Medtronic: 0.949, Evita vs. Medtronic: 0.878). The correlation of PaCO 2 with the Evita is the lowest (0.671) as compared to the EMMA (0.693) and the Medtronic (0.727). The lowest dispersion of the difference between etco 2 and PaCO 2 was seen in EMMA (3.30), the highest in Evita (3.98). Conclusions: A good correlation between etco 2 and PaCO 2 was shown with the three capnometers in the present study. However, etco 2 measurements were not valid to estimate PaCO 2 in these patients. Therefore, capnometry cannot be used to replace serial blood gas analyses completely, but may be a good cardiopulmonary trend monitor and alerting system in catastrophic events. Ó 2013 Elsevier Inc., Keywords end-tidal carbon dioxide; capnography; capnometer; monitoring; carbon dioxide; blood gas analysis INTRODUCTION Since the first infrared carbon dioxide measuring and recording apparatus was introduced in 1943 by Luft, capnography has evolved into an essential component of the American Society of Anesthesiology standard anesthesia monitoring armamentarium to monitor cardiopulmonary function and to prevent hypoxia. End-tidal carbon dioxide (etco 2 ) is a surrogate, noninvasive measurement of partial pressure of arterial CO 2 (PaCO 2 ). The utility of capnography has in recent times been extended outside of the operating room to the intensive care unit (ICU), Emergency Department (ED), endoscopic suites, x-ray rooms, and on-site at emergency and trauma fields. The most important clinical applications are confirmation of endotracheal intubation, noninvasive monitoring of ventilation, and assessment of cardiac output (1 4). Determination of etco 2 is very helpful in cardiac resuscitation, as an indicator of return of circulation RECEIVED: 27 January 2012; FINAL SUBMISSION RECEIVED: 14 June 2012; ACCEPTED: 5 November

2 Accuracy of etco 2 Capnometers 131 and adequacy of chest massage because it is linked to cardiac output. The new Advanced Cardiovascular Life Support guidelines recommend the use of quantitative waveform capnography for confirmation and monitoring of endotracheal tube (ETT) placement and effectiveness of chest compressions (5). Several new capnometers are now being developed especially for use in trauma, Emergency and cardiopulmonary resuscitation settings. In our hospital, three different capnometers are used, the Medtronic and EMMA capnometers and the Evita in-ventilator capnometer. The Medtronic and EMMA capnometers are lightweight and easy transportable devices. In addition, the EMMA is small and does not need warm-up time or calibration before display of etco 2 values starting directly after the first breath. Both can be connected easily to an ETT, laryngeal mask, or facial mask. Therefore, these capnometers appear very useful in the ED during intubation and resuscitation and during patient transfer. A disadvantage of the EMMA is the lack of graphic display. The Evita is an in-ventilator capnometer with graphic display and therefore more suitable in the ICU. Accuracy of these capnometers has not been studied thoroughly in different settings. We, therefore, compared the accuracy of these three capnometers in sedated and ventilated postoperative cardiac surgical patients. METHODS After approval from the local ethics committee, 40 elective cardiac surgery patients undergoing coronary artery bypass grafting and valve replacement were included in this prospective study. All adult patients were sedated and ventilated without spontaneous breathing activity in the ICU. Exclusion criteria were chronic obstructive pulmonary disease of GOLD (Global Initiative for Chronic Obstructive Lung Disease) III or more and hemodynamic instability, defined as a systolic blood pressure <90 mm Hg, dobutamine >5 mg kg 1 min 1 per min or norepinephrine >0.1 kg 1 min 1 (6). Three capnometers were tested. The EMMA Emergency Capnometer (Phasein Medical Technologies, Danderyd, Sweden; mainstream sampling), the integrated capnography within the Evita-4 respirator (Draeger, Lubeck Germany, software version ; mainstream sampling), and the Medtronic Lifecap capnometer with a microstream circuit (Medtronic, Redmond, WA; sampling rate: 50 ml, min 1 ). All three capnometers were placed in the order mentioned from proximal to distal in the ventilator tubing of the patient. The PaCO 2 was measured with the Bayer Blood Gas Analyzer 865 (Bayer HealthCare, Tarrytown, NY). Patient s ETT was connected to the capnometers via a connector swivel gibeck with heat and moisture exchanger HUMID-VENT Filter Compact (Teleflex Medical, Kernen, Germany). The capnometers were all calibrated to conform to the guidelines of the manufacturers. The total additional resistance of the filter, swivel, and three capnometers in a row was 2.64 cmh 2 OL 1 s. All patients were sedated with propofol 1 to 3 mg kg 1 h 1 to achieve a Ramsay sedation score of 5. Patients were ventilated using an Evita-4 (Draeger, Lubeck, Germany) ventilator on intermittent positive pressure ventilation with autoflow, flow trigger 5 L min 1, tidal volume of 8 ml kg 1 predicted body weight, frequency depending on the minute volume ventilation needed to be normocapneic, positive end expiratory pressure 8 cmh 2 O, and FiO Expiration time was set in order for expiration flow to return to zero so no intrinsic positive end expiratory pressure occurs. After connection of the capnometers, 4 min of stabilization time was allowed before starting to collect data. Twenty consecutive etco 2 values of 20 consecutive exhalations were collected simultaneously from all three monitors while drawing an arterial blood sample at the same time in each patient; the mean of these 20 etco 2 values was used in the data analyses. Data were presented as number (percentage) for categorical variables and as mean 6 standard deviation or standard error of mean, or with 95% confidence interval and interquartile range for continuous variables. Paired sample t-test was used to compare the mean values between the three capnometers and PaCO 2. Pearson correlation was used to study the correlation between all three capnometers and the correlation between capnometers and PaCO 2. Individual pair-wise differences between the capnometers and PaCO 2 were presented by Bland- Altman plots. A p value #0.05 was considered statistically significant. All analyses were performed with SPSS version (IBM SPSS, Armonk, NY). Patients RESULTS Forty post-cardiac surgery patients with a mean age of 68 years were analyzed. Patient characteristics are shown in Table 1. Differences in etco 2 Between All Three Capnometers There was no significant difference in mean etco 2 value between the Evita capnometer as compared to the Medtronic. The differences in etco 2 between the EMMA and Evita and between EMMA and Medtronic were significant. The EMMA consistently measures a lower value of etco 2 as compared to the Evita and Medtronic.

3 132 S. J. H. Heines et al. Table 1. Patient Characteristics (n = 40) Patient Characteristics Male sex, n (%) 30 (75) Age (y), mean 6 SD CABG, n (%) 24 (60) Valve replacement, n (%) 10 (25) CABG and valve, n (%) 6 (15) Length (cm), male/female, mean 6 SD / Weight (kg), male/female, mean 6 SD / Smoking, n (%) 12 (30) COPD <GOLD III, n (%) 4 (10) SD = standard deviation; CABG = coronary artery bypass grafting; COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease. The lowest dispersion of the difference between etco 2 was seen with EMMA and Medtronic, the dispersion between Evita and Medtronic and between EMMA and Evita was nearly the same (Table 2). Difference Between etco 2 and PaCO 2 The difference in etco 2 between all the capnometers and PaCO 2 was significant. The mean value of etco 2 in all the capnometers was lower as compared to PaCO 2, with the greatest difference between EMMA and PaCO 2. The lowest dispersion of the difference between etco 2 and PaCO 2 was seen in EMMA, the highest in Evita (Table 2). Correlation Between Capnometers and etco 2 vs. PaCO 2 The correlation of etco 2 measurements between all three capnometers was strong, the EMMA and Medtronic capnometer had the strongest correlation (0.949) (Evita vs. Medtronic 0.878; EMMA vs. Evita 0.874). The correlation of PaCO 2 with the Evita is the weakest (0.671) as compared to the EMMA (0.693) and the Medtronic (0.727) (Table 2). Figures 1 to 6 show Bland-Altman plots of the mean etco 2 in relation to the difference between etco 2 from the Evita, Medtronic, EMMA, and PaCO 2. DISCUSSION The correlation between the three capnometers was good, but correlation with PaCO 2 was suboptimal in the immediate postoperative setting of ventilated cardiac surgical patients. These findings are in accordance with previous studies (7,8). It was shown that in healthy ventilated patients, the etco 2 is an underestimate of the PaCO 2 by approximately 4 mm Hg, and a slightly positive PaCO 2 -etco 2 gradient is therefore produced. In case of pulmonary parenchymal disease, the etco 2 is the sum of the alveolar CO 2 tensions from areas of widely differing ventilation-perfusion ratios and emptying times. Increased positivity of the PaCO 2 -etco 2 gradient occurs because of the continued ventilation of alveoli that are no longer perfused (i.e., there is an enlargement of the regions of the lung with high ventilation perfusion ratios). The difference in patients with severe pulmonary disease may be up to 20 mm Hg (9). Other conditions that might lead to increased positivity of the gradient are hypovolemia with decreased pulmonary artery pressure, excessive positive end-expiratory pressure with increased alveolar pressure, pulmonary vascular occlusive disease, and venous air embolism. The mean difference between PaCO 2 and etco 2 after cardiac surgery in 300 tested patients in our unit was 6.83 mm Hg; there were 6 patients with a negative gradient (2%) (unpublished data) that was lower, as reported by Russell et al. (8.1%) (10). The etiology of the negative gradient is not entirely clear (8,11). Using etco 2 to predict PaCO 2 should be done with caution, especially in cases that involve pulmonary disorders and acid base imbalance. Nevertheless, Table 2. Paired Sample t-test, Medians, and Interquartile Range of the Mean Difference in End-Tidal Carbon Dioxide Values Between Three Capnometers, EMMA, Evita, Medtronic, and Partial Pressure of Arterial CO 2 Paired Differences Association Between n Mean Difference Median Difference SEM Significance (2-Tailed) 95% CI of the Difference Lower Upper Correlation IQR Emma vs. Evita <0.001* Emma vs. Medtronic <0.001* Evita vs. Medtronic Emma vs. PaCO <0.001* Evita vs. PaCO <0.001* Medtronic vs. PaCO <0.001* CI = confidence interval; IQR = interquartile range; PaCO 2 = partial pressure of arterial CO 2 ; SEM = standard error of mean. Data are end-tidal carbon dioxide in mm Hg. * p < Pearson correlation between EMMA, Evita, and Medtronic capnometers and PaCO 2.

4 Accuracy of etco 2 Capnometers 133 Figure 1. Bland-Altman plot of the mean end-tidal CO 2 (etco 2 ) from the EMMA and Evita (mean EMMA-Evita) in relation to the difference between etco 2 from the EMMA minus the Evita (difference EMMA-Evita). Red dotted line indicates the mean difference in etco 2 between the EMMA and Evita. Figure 3. Bland-Altman plot of the mean end-tidal CO 2 (etco 2 ) from the Evita and Medtronic (mean Evita- Medtronic) in relation to the difference between etco 2 from the Evita minus the Medtronic (difference Evita-Medtronic). Red dotted line indicates the mean difference in etco 2 between the Evita and Medtronic. capnography can be a useful trend indicator when the mean differences between etco 2 and PaCO 2 remain consistent over time. In addition, capnography is a very good alert system in case of cardiopulmonary emergencies. Capnography has been recognized by many leading associations and organizations as a standard of care in many clinical and preclinical settings (12). Mainstream capnometers measure exhaled CO 2 directly in-line with the sensor located between the ETT and the ventilator circuit. Sidestream capnometers withdraw a sample of gas from the circuit for analysis. Sidestream capnometers are lightweight so the potential for kinking of the ETT or ventilatory circuit is less than compared to mainstream capnometers (13). The Medtronic sidestream capnometer was placed most distal of the patient because sampling of gas in the proximal position could influence etco 2 for the other capnometers. However, in a pilot study, the order of placement of the capnometers did not bias the results (unpublished data). Figure 2. Bland-Altman plot of the mean end-tidal CO 2 (etco 2 ) from the EMMA and Medtronic (mean EMMA- Medtronic) in relation to the difference between etco 2 from the EMMA minus the Medtronic (difference EMMA- Medtronic). Red dotted line indicates the mean difference in etco 2 between the EMMA and Medtronic. Figure 4. Bland-Altman plot of the mean end-tidal CO 2 (etco 2 ) from the EMMA and PaCO 2 (mean Emma-PaCO 2 ) in relation to the difference between etco 2 from the Emma minus PaCO 2 (difference Emma-PaCO 2 ). Red dotted line indicates the mean difference in etco 2 between the EMMA and PaCO 2.

5 134 S. J. H. Heines et al. etco 2 values or under different circumstances remains to be established. CONCLUSIONS Figure 5. Bland-Altman plot of the mean end-tidal CO 2 (etco 2 ) from the Evita and PaCO 2 (mean Evita-PaCO 2 ) in relation to the difference between etco 2 from the Evita minus PaCO 2 (difference Evita-PaCO 2 ). Red dotted line indicates the mean difference in etco 2 between the Evita and PaCO 2. Limitations The limitations of this study are that we did not measure etco 2 for a longer period in each patient to see if the positive PaCO 2 -etco 2 gradient stays consistent over time. In addition, the study was performed in a stable, essentially normocapneic, group of post-cardiothoracic surgery patients at the time of presentation in the ICU. Whether the result applies to other patient groups who are not normocapneic and have more extreme outlier Figure 6. Bland-Altman plot of the mean etco 2 from the Medtronic and PaCO 2 (mean Medtronic-PaCO 2 ) in relation to the difference between etco 2 from the Medtronic minus PaCO 2 (Difference Medtronic-PaCO 2 ). Red dotted line indicates the mean difference in etco 2 between the Medtronic and PaCO 2. All ventilators should have a build-in capnometer with the possibility for display. The Medtronic and EMMA capnometers are lightweight and easy transportable devices, the lack of graphic display in the EMMA is a disadvantage. A good correlation between etco 2 and PaCO 2 was shown with the three capnometers tested in the present study. However, there is a consistent difference between etco 2 measurement and PaCO 2. Therefore, etco 2 measurements are not reliable to estimate PaCO 2 in these postoperative ventilated cardiac surgery patients. Capnometry cannot be used to replace serial blood gas analyses completely. REFERENCES 1. Knapp S, Kofler J, Stoiser B, et al. The assessment of four different methods to verify tracheal tube placement in the critical care setting. Anesth Analg 1999;88: Poirier MP, Gonzalez Del-Rey JA, McAneney CM, DiGiulio GA. Utility of monitoring capnography, pulse oximetry, and vital signs in the detection of airway mishaps: a hyperoxemic animal model. Am J Emerg Med 1998;16: Tyburski JG, Collinge JD, Wilson RF, Carlin AM, Albaran RG, Steffes CP. End-tidal CO2-derived values during emergency trauma surgery correlated with outcome: a prospective study. J Trauma 2002;53: Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med 1997; 337: Field JM, Hazinski MF, Sayre MR, et al. Part 1: executive summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(18 Suppl 3):S Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001;163: Wahba RW, Tessler MJ. Misleading end-tidal CO2 tensions. Can J Anaesth 1996;43: Russell GB, Graybeal JM. Reliability of the arterial to end-tidal carbon dioxide gradient in mechanically ventilated patients with multisystem trauma. J Trauma 1994;36: Benumof JL. Interpretation of capnography. AANA J 1998;66: Russell GB, Graybeal JM, Strout JC. Stability of arterial to end-tidal carbon dioxide gradients during postoperative cardiorespiratory support. Can J Anaesth 1990;37: Shankar KB, Moseley H, Kumar Y, Vemula V. Arterial to end tidal carbon dioxide tension difference during caesarean section anaesthesia. Anaesthesia 1986;41: Schreiter D, Reske A, Stichert B, et al. Alveolar recruitment in combination with sufficient positive end-expiratory pressure increases oxygenation and lung aeration in patients with severe chest trauma. Crit Care Med 2004;32: Bhende M. Capnography in the pediatric emergency department. Pediatr Emerg Care 1999;15:64 9.

6 Accuracy of etco 2 Capnometers 135 ARTICLE SUMMARY 1. Why is this topic important? Capnography is widely used with different and new capnometers. The utility of capnography has in recent times been extended outside of the operating room arena to intensive care units, Emergency Department, endoscopic suites, x-ray rooms, and on-site at emergency and trauma fields. 2. What does this study attempt to show? It is important to know the accuracy of the capnometers and its correlation with partial pressure of arterial CO 2 (PaCO 2 ). 3. What are the key findings? All three capnometers correlate well with each other and with PaCO 2. However, there is a great individual difference in end-tidal carbon dioxide and PaCO How is patient care impacted? Capnometry is likely to be useful to monitor trends in relation to PaCO 2 but cannot be used to replace serial blood gas analyses completely.