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Samuel M. Galvagno Jr., D.O.
Bhavani Shankar Kodali, M.D.


The value of Capnography is very well appreciated in the operating rooms and anesthesiologists have been well trained to rely on this valuable source of information in decision making. However, when the patient arrives into the intensive care unit (ICU), the patient is deprived of the benefits of this valuable monitor. This is most likely due to the paucity of capnographs in ICU, lack of hands on practical experience with capnography among intensivists and ICU nurses, lack of adequate maintenance of the capnography system resulting in malfunctions and subsequent nonuse, and deeply enrooted protocol driven ICU’s with a historical tradition of depending heavily on the excessive use of arterial blood gases. This chapter will focus on reinforcing the value of capnography in the ICU’s and discuss several potential benefits it could offer in the management of critically ill patients.
The measurement of carbon dioxide (CO2) in expired air directly indicates changes in the elimination of CO2 from the lungs. Indirectly, it indicates changes in the production of CO2 at the tissue level and in the delivery of CO2 to the lungs by the circulatory system.  Capnography is a non-invasive monitoring technique that allows fast and reliable insight into ventilation, circulation, and metabolism.  Capnographs provide both a waveform and digital reading of end-tidal CO2 (ETCO2 - maximum concentration of carbon dioxide at the end of a breath).  The digital reading for ETCO2 is often displayed as mm Hg (partial pressure of CO2 in exhaled gas) or as % in exhaled gas.


Measurement and location of exhaled carbon dioxide:

Most of the commonly used devices use infrared absorption of CO2 as a principle of operation (See physics).1 A known concentration of infrared light is traversed through the exhaled gases. Carbon dioxide, being a poly atomic gas, absorbs infrared light. The remaining beam of light is detected by detectors and exhaled CO2 values are computed.  Based on the location of the sensors, the capnographs are classified into two types; main-stream sensors and side-stream sensors. 


Side-stream capnography:


With side-stream capnography, the CO2 sensor is located in the main unit itself, away from the patient, and a pump aspirates gas samples from the patient’s airway through a 6 foot capillary tube into the main processing unit.  One advantage of side-stream capnography is that expiratory gases can be obtained from the nasal cavity using nasal adaptors or with a simple modification of the standard nasal cannula.  These devices are easy to connect, do not require sterilization as they are disposable, and can be used in awake patients.  The capnographs will have a delay in displaying CO2 concentration as expired gases have to transit from the airway via the tubing into the unit. A main problem encountered in the ICU setting is the blockage of the sampling tubes by water vapor and secretions. Interposing filters at either end of the sampling tubes, and positioning the sampling tube upwards towards the monitor minimizes this problem.

Main-stream capnography:

In main-stream capnographs, a sample cell or cuvette, usually in the form of an airway adapter, is inserted directly in the airway between the breathing circuit and the endotracheal tube, or airway device.  A lightweight infrared sensor is attached to the airway adapter and emitted light is detected by a photo detector located on the opposite side of the airway adapter.  This sampling technique produces waveforms that reflect real-time CO2 measurements during a respiratory cycle without a delay.  Contrary to earlier versions, new sensors are lightweight and minimize traction on the endotracheal tube.  Sensor windows may clog with secretions and condensation; however, they can be replaced easily, as they are disposable.  Positioning the cuvette distal to the suctioning unit of the endotracheal tube can, to some extent, prevent the contamination of CO2 sensors.


Colorimetric devices:


Colorimetric devices provide continuous, semiquantitative end-tidal CO2 monitoring.  A typical device has 3 color ranges.  A purple color corresponds to an ETCO2 level < 0.5%, a tan color indicates ETCO2 of 0.5-2%, and a yellow color indicates ETCO2 > 2%.  Normal end-tidal CO2 is > 4%; hence, the device should turn yellow when the endotracheal tube is inserted in patients with intact circulation.  Confirmation of endotracheal tube placement in non-cardiac arrest patients is not always reliable. The membrane can turn yellow when the device is contaminated with acidic substances such as gastric acid, lidocaine, or epinephrine resulting in false positive readings. 
False negative readings, defined as a failure to detect CO2 despite confirmed endotracheal tube placement in the trachea, may occur during cardiac arrest.  In the low-flow hypodynamic state of cardiac arrest, delivery of CO2 to the lungs is decreased and color changes may not appreciated.
Recently, small portable electronic infra red devices with quick warming time have been introduced into the practice for use outside of ICU/operating rooms.

Physiology

Carbon dioxide concentration can be plotted against time or expired volume. A time capnogram (see physiology) can be divided into inspiratory and expiratory segments (phase 0). (1, 2) The inspiratory segment is further divided into three phases; phase I (dead space gases), phase II (mixture of dead space and alveolar gases), and phase III (alveolar gases).  Phase III reflects alveolar evolution of CO2 and always has a mild positive upslope. This positive upslope is not well appreciated in a time capnogram as majority of expiration is completed during the early phase of expiration. On the other hand, volume capnogram, the positive slope is prominent as CO2 concentration is plotted against evolving expiratory volume. It has no inspiratory segment.  Volume capnography is much more beneficial in the ICU setting. The volume capnogram can be related to components of tidal volume; physiological dead space and alveolar ventilation (see physiology). A noninvasive estimate of physiological dead space can be obtained from volume capnography. 

Arterial to end-tidal CO2 (a-ET)CO2 gradient as an index of alveolar dead space:

Under normal circumstances, the PETCO2 (the CO2 recorded at the end of the breath which represents PCO2 from alveoli which empty last) is lower than PaCO2 (average of all alveoli) by 2-5 mmHg, in adults. The (a-ET)PCO2 gradient is due to the V/Q mismatch in the lungs (alveolar dead space) as a result of temporal, spatial, and alveolar mixing defects. In healthy children, the (a-ET)PCO2 gradient is smaller (-0.65-3 mm Hg) than in adults. This is due to a better V/Q matching, and hence a lower alveolar dead space in children than in the adults.3 The (a-ET)PCO2 / PaCO2 fraction is a measure of alveolar dead space, and changes in alveolar dead space correlate well with changes in (a-ET)PCO2. (4) An increase in (a-ET)PCO2 suggests an increase in dead space ventilation. Hence (a-ET)PCO2 is an indirect estimate of V/Q mismatching of the lung. Increases in alpha angle (angle between phase II and phase III) and the slope of phase III are a good refection of V/Q perfusion status of the lung. In chronic obstructive airway disease, the slope of phase III is increased together with an increase in the alpha angle. The morphology of capnogram can offer tremendous information about underlying V/Q abnormality.

Cardiac output and (a-ET)PCO2

Decreases in cardiac output and pulmonary blood flow result in decreases in PETCO2 and an increase in (a-ET)PCO2. Increases in cardiac output and pulmonary blood flow result in better perfusion of the alveoli and a rise in PETCO2. (5,6) Consequently alveolar dead space is reduced as is (a-ET)CO2 The decrease in (a-ET)PCO2 is due to an increase in the alveolar CO2 with a relatively unchanged arterial CO2 concentration, suggesting better excretion of CO2 into the lungs. The improved CO2 excretion is due to better perfusion of upper parts of the lung. (6)  Askrog found an inverse linear correlation between pulmonary artery pressure and (a-ET)PCO2. (6)  Thus, under conditions of constant lung ventilation, PETCO2 monitoring can be used as a monitor of pulmonary blood flow. (5,7)

 Clinical applications
 
(1) Confirmation of Endotracheal Intubation


Numerous national organizations, including the American Heart Association, now endorse capnography and capnographic methods for confirming endotracheal tube placement. (8)  Despite these recommendations, capnography is not always widely available nor consistently applied. (9) Although no study, to date, has shown a single device to be 100% sensitive and specific for determining proper endotracheal tube placement, capnography should be considered as a mandatory adjunct to confirm correct endotracheal tube.  In one ICU intubation study, esophageal intubation occurred in 25 of the 297 (8%) intubation procedures. (101)  Only 10 of 25 (40%) procedures that resulted in esophageal intubation met the criteria for difficult intubation. During 22 of the 25 intubations, the esophagus was intubated only once before tracheal intubation was accomplished.  In the remaining three, the esophagus was intubated a total of 13 times before successful completion of tracheal intubation. Thus, there were 35 esophageal intubations among the 25 procedures. Of the 35 esophageal intubations, 32 were recognized by clinical criteria, which included auscultation of breath sounds and gastric distention. Three esophageal intubations were not recognized until there was a decrease in the oxyhemoglobin saturation as measured by pulse oximetry. (10)  Two of the esophageal intubations were associated with new infiltrates in chest radiographs.  Patients in ICU have a decreased margin of safety in terms of oxygen reserves and an unrecognized esophageal intubation can result in severe hypoxemia progressing to cardiac arrest and ultimately death. Therefore, during emergent intubation, the correct placement of the endotracheal tube should be confirmed immediately.  A decrease in oxyhemoglobin saturation, as measured by pulse oximetry, might detect an otherwise unrecognized esophageal intubation. However, this recognition may be delayed because of the use of oxygenation before intubation and by alveolar ventilation (with room air) via diaphragmatic movement produced by esophageal intubation and gastric ventilation. (11)
Studies have shown that end-tidal CO2 detectors are useful for confirmation of correct endotracheal tube placement. (12) The sensitivity in these studies has been described as ranging from 20-100%, but the specificity (percentage of incorrect esophageal placement detected when no CO2 is detected) has ranged from 97-100%. (13) Therefore, the positive predictive value (probability of correct endotracheal tube placement if CO2 is detected) is nearly 100% while the negative predictive value (probability of esophageal tube placement if no CO2 is detected) has a broader range of 20-100% (American Heart Association, 2005).  CO2 can occasionally be detected when the tube is placed in the esophagus; false positive CO2 determinations have been found in animals that have ingested large amounts of carbonated liquids in a cardiac arrest model. (14)
Despite the above controversies, it seems simply illogical in the present times not to use capnography to confirm correct endotracheal tube placement when capnography is considered as a standard of care in the operating rooms. This is echoed by Schwartz et al. in the above study; they cared for a patient after the completion of the study in whom an esophageal intubation was not detected clinically before death. Therefore, they state in the discussion that although the detection of exhaled carbon dioxide after tracheal intubation in critically ill patients has not been rigorously studied, they believe it should be used to provide additional confirmatory evidence whenever possible. (10)


(2)  Monitoring of patients during positional changes in ICU:


ICU patients require frequent changes in position. Capnography will help to monitor the integrity of the patient’s airway during changes in position. Partial endotracheal tube obstruction resulting from either kinking of endotracheal tube, or by secretions can be detected via continuous monitoring of CO2 waveforms. Prolongation of phase II and sloping phase III suggest obstruction of the endotracheal tube.


(3) Assessment of cardiac output:


As stated in the physiology, the percent decrease in PETCO2 directly correlated with the percent decrease in cardiac output (slope= 0.33, r2=0.82 in 24 patients undergoing aortic aneurysm surgery with constant ventilation).(15) Also, the percent decrease in CO2 elimination correlated with the percent decrease in cardiac output similarly (slope=0.33, r2=0.84).(3) Increases in cardiac output and pulmonary blood flow result in better perfusion of the alveoli and a rise in PETCO2. (5, 6) The relationship between PETCO2 and pulmonary artery blood flow was studied during separation from cardiopulmonary bypass.(4) This showed that PETCO2 is a useful index of pulmonary blood flow. A PETCO2 > 30 mm Hg was invariably associated with a cardiac output more than 4 L/min or a cardiac index > 2 L/min.4 Furthermore, when PETCO2 exceeded 34 mm Hg, pulmonary blood flow was more than 5 L/min (CI > 2.5 L).(16) Thus, under conditions of constant lung ventilation, PETCO2 monitoring can be used as a monitor of pulmonary blood flow. (16-19) This strong physiological relationship between ETCO2 and cardiac output qualifies capnography to be considered as a relevant and useful tool to monitor cardiac output in critically ill hemorrhagic patients. 

Based on the well-known accepted Fick's Principle, Respironics, Connecticut, USA introduced NICO (Respironics, NICO®) cardiac output measurement device that uses partial CO2 breathing to determine cardiac output non-invasively. The NICO® Cardiopulmonary Management System provides continual cardiac output monitoring. With this method, the cardiac output is computed from breath-by-breath measurements of CO2 elimination. Rebreathing measurements are made every three minutes for 35 seconds. Cardiac output is proportional to the change in CO2 elimination divided by the change in end tidal CO2 resulting from a brief rebreathing period. These measurements are accomplished and measured by the proprietary NICO Sensor, which periodically adds a rebreathing volume into the breathing circuit. In addition, NICO provides non invasive measurement of airway dead space. If arterial carbon dioxide tensions are known, physiological dead space can be calculated easily.  Several investigators have used this device to determine cardiac output and compare the results with conventional methods, such as pulmonary artery catheter measurements. The results are encouraging in patients with healthy lungs. (20-23) Whereas the results are controversial when the lungs are diseased. (24)


(4) Capnography as a Prognostic Indicator during cardiopulmonary resuscitation (CPR):


As discussed above, the relationship between cardiac output and end-tidal CO2 is logarithmic. (25) Capnography can detect the presence of pulmonary blood flow even in the absence of major pulses (pseudo-electromechanical dissociation) and also can rapidly indicate changes in pulmonary blood flow (cardiac output) caused by alterations in cardiac rhythm. (26)
Data suggests that the end-tidal CO2 correlates well with coronary perfusion pressure. (27) This correlation between perfusion pressure and end-tidal CO2 is likely to be secondary to the relationship of end-tidal CO2 and cardiac output.
Capnographic measurements have been evaluated as a prognostic indicator of outcome in cardiac arrest.  In a study of 127 patients, all but 1 patient with an end-tidal CO2 value less than 10 mm Hg died before discharge. (28)  The results of this study were confirmed with another prospective investigation involving 139 adult victims of out-of-hospital, non-traumatic cardiac arrest. (29)  None of the patients with an average, initial, and final end-tidal CO2 level of less than 10 mm Hg were successfully resuscitated.  The authors concluded that end-tidal CO2 monitoring can be correlated with resuscitation outcome in CPR.
Indirect but an important application of capnography in CPR is to provide feedback to optimize chest compressions during CPR. Monitoring ETCO2 during CPR may detect unrecognized fatigue-induced inadequate chest compressions that result in less than desirable cardiac output.
(5)  Capnography during trauma resuscitation
End-tidal CO2 is a marker of pathophysiological state encountered in trauma since it reflects cardiac output.  ETCO2 may be of value in predicting outcome from major trauma.  In a study of 191 blunt trauma patients, only 5% of patients with an end-tidal CO2 determination of < 10 mm Hg survived to discharge. (30)    Other studies have shown capnography to be of value in providing optimum ventilation in prehospital major trauma victims.  The incidence of normoventilation was significantly higher (63.2% vs. 20%, p<0.0001) in a group of patients who were monitored with capnography in the field compared to those without it. (31).  


(6) Capnography as a non invasive monitoring of ventilation


Continuous ETCO2 can be used to optimize ventilation to the desired level of PaCO2. Usually, the arterial levels are higher by about 5 mm Hg. This difference can vary with varying V/Q mismatch in the lungs. If the patient has chronic obstructive lung disorder or unstable cardiac outputs, the ETCO2 may not be a perfect guide to ventilation. However, in those patients where the lungs are essentially normal and cardiac output is in reasonable range, such as head injury patients, the ECTO2 can be used to noninvasively monitor PaCO2. An initial arterial blood gas can be performed to determine the (a-ET)PCO2 difference, and further adjustments can be made using PETCO2 as a guide. This can minimize unnecessary arterial blood gas evaluations and can decrease cost of care.  In a recent study, the patterns of utilization of arterial blood gas (ABG) tests in a large tertiary care hospital were studied. (32) The investigators analyzed 491 ABG tests performed during 24 two-hour intervals, representative of different staff shifts throughout the 7-day week. The clinician ordering each ABG test was asked to fill out a utilization survey. The most common reasons for requesting an ABG test were changes in ventilator settings (27.6%), respiratory events (26.4%), and routine (25.7%). Of the results, approximately 79% were expected, and a change in patient management (e.g., a change in ventilator settings) occurred in 42% of cases. Many ABG tests were ordered as part of a clinical routine or to monitor parameters that can be assessed clinically or through less invasive testing. Capnography was not utilized in this unit and that would have probably decreased the need for frequent ABG’s.
Arterial to end tidal CO2 difference also gives a fair idea about physiological dead space in the patient. If the gradient stabilizes or it decreases over a period of time from an initially large gradient, this demonstrates indirectly that the patients V/Q status is improving with therapy. The value of capnography in these instances is often under estimated.


(7) Detection of inadvertently placed gastric tube in the trachea:


Recently calorimetric as well as capnography has been used to detect inadvertent tracheal insertion of gastric tubes.  One study compared capnography and colorimetric device in detecting tracheal placement of gastric tubes in a variety of circumstances. Carbon dioxide was successfully detected by the colorimetric indicator within in seconds in all insertions in which carbon dioxide was detected by capnography. When carbon dioxide was detected (27% of insertions), the tubes were withdrawn and reinserted. Carbon dioxide detection during gastric tube placement was significantly associated with nasal insertions (P =0 .03) and spontaneously breathing/nonintubated status (P =0 .01) but not with mental status or tube type. (33)


(8) Percutaneous dilatational tracheostomy:


Percutaneous tracheostomy is increasingly performed in intensive care units. The intensive care units have developed their own guidelines to minimize complication rate. These guidelines focus on preoperative risk assessment including levels of ventilatory support and anatomical considerations, seniority of staff, use of bronchoscopy, correction of coagulopathies, and the use of capnography. In a study utilizing these guidelines, the authors found an immediate decrease in major and minor complications during and following the percutaneous tracheostomy procedure. (34)  In another study, the authors used capnography in 26 patients and bronchoscopy in 29 patients to confirm needle placement for percutaneous tracheostomy using Blue Rhino kit. The operating times and the incidence of peri-operative complications were similar for both groups. They concluded that capnography proved to be as effective as bronchoscopy in confirming correct needle placement. (35) Coleman et al. also used capnography to confirm intratracheal cannula placement prior to percutaneous dilatational tracheostomy and they found capnography to be reliable in confirming the correct position of tracheal cannula. (36) These studies suggest the value of capnography in percutaneous dilatational tracheostomy even in the absence of bronchoscopy.


Recent advances in capnography in ICU:


Studies are evaluating the utility of derived dead space indexes to predict survival in mechanically ventilated patients with acute lung injury (ALI) and ARDS. In one study, the authors studied 36 patients with ALI, measurements included respiratory system compliance; capnographic indexes (Bohr dead space) and physiologic dead space (Enghoff dead space [Vdphys/Vt]), expired normalized CO2 slope, carbon dioxide output, and the alveolar ejection volume (Vae)/tidal volume fraction (Vt) ratio. The best predictor was the Vae/Vt ratio at ICU admission (Vae/Vt-adm) and after 48 h (Vae/Vt-48 h) [p = 0.013], with a sensitivity of 82% and a specificity of 64%. The difference between Vae/Vt-48 h and Vae/Vt-adm showed a sensitivity of 73% and a specificity of 93% with a likelihood ratio (LR) of 10.2 and an area under the receiver operating characteristic (ROC) curve of 0.83. The interaction between the PaO2/FiO2 ratio and Vae/Vt-adm predict survival (p = 0.003) with an area under the ROC curve of 0.84, an LR of 2.3, a sensitivity of 100%, and a specificity of 57%. The Vdphys/Vt after 48 h predicted survival (p = 0.02) with an area under the ROC curve of 0.75, an LR of 8.8, a sensitivity of 63%, and a specificity of 93%. The authors concluded that noninvasive measures of Vae/Vt at ICU admission and after 48 h of mechanical ventilation provided useful information on outcome in critically ill patients with ALI. (37)


Association between deadspace/tidal volume ratio (Vd/Vt) and gas exchange variables:

PaO2, PacO2, PaO2/FiO2, arterial/alveolar oxygen tension ratio (PaO2/PAO2), alveolar-arterial oxygen tension difference/arterial oxygen tension ratio (P(A-a)O2/PaO2), carbon dioxide production (VCO2), ventilation index ([PaCO2 x peak inspiratory pressure x mechanical respiratory rate]/1000), and oxygenation index ([mean airway pressure x FiO2 x 100]/PaO2), are being investigated in early stage in children with obstructive acute respiratory failure. In one study, the measurements were derived using volumetric capnography and arterial blood gas analysis. Results suggest a significant association between an increase in Vd/Vt and severity of lung and disturbances of oxygenation.  Further evaluation of the usefulness of serial measurement of Vd/Vt as a marker of disease severity in severe acute bronchiolitis and other causes of respiratory failure are warranted. (38)
Investigators are also evaluating single breath tracing for carbon dioxide in septic patients with tissue hypoxia. Single breath tracing for carbon dioxide (SBT-CO2, volume capnogram) was analyzed in 18 ICU septic patients. Nine patients had tissue hypoxia events. Using the Hill formula, all tracings were analyzed point by point to obtain the time required for CO2 to achieve 50% maximal value and the Fractional Expiratory Time 50 (FET0.5). Carbon dioxide CO2 clearance and FTE 0.5 derived in hypoxic patients were compared with those in non-hypoxic patients. In the hypoxic group CO2 clearance and FET0.5 values were higher than those in the non hypoxic group. Furthermore, CO2 clearance correlated with arterial lactate and base excess in hypoxic patients. (39)


Morphology of CO2 Wave forms:


Morphology of CO2 waveforms (see clinical applications) provides immediate diagnostic clues and therapeutic effectiveness of therapies in the clinical management of critical patients. The CO2 waveform is identical in every individual with healthy lungs. Any deviation from the normal must be investigated for a physiological or pathological cause. Apart from circuit disconnections and ventilatory failures resulting in apneic capnograms, capnography waveforms provide dynamic information about airway caliber. Capnograms in asthma are shown in figure 6A and therapeutic effectiveness after using bronchodilators is shown in 6B.  Capnography is useful in the weaning of patients from mechanical ventilation. A close similarity between spontaneous ventilation capnogram and intermittent mandatory breath capnograms suggests the possibility of return of adequate spontaneous respiratory effort. In addition, capnography also facilitates monitoring of spontaneous ventilation after weaning, or during sedation procedures. (1)
In summary, capnography is a key component in the monitoring standards in the operating room. When the same patient arrives in ICU, it seems not logical to discontinue capnography. Once the science around and within CO2 curves is understood by the clinicians and nursing staff, it will become utterly difficult to disregard this valuable monitor as it provides critical data about patient’s cardiorespiratory status.

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