Capnography as a tool to detect metabolic changes in patients cared for in the emergency setting

ABSTRACT Objective: to evaluate the usefulness of capnography for the detection of metabolic changes in spontaneous breathing patients, in the emergency and intensive care settings. Methods: in-depth and structured bibliographical search in the databases EBSCOhost, Virtual Health Library, PubMed, Cochrane Library, among others, identifying studies that assessed the relationship between capnography values and the variables involved in blood acid-base balance. Results: 19 studies were found, two were reviews and 17 were observational studies. In nine studies, capnography values were correlated with carbon dioxide (CO2), eight with bicarbonate (HCO3), three with lactate, and four with blood pH. Conclusions: most studies have found a good correlation between capnography values and blood biomarkers, suggesting the usefulness of this parameter to detect patients at risk of severe metabolic change, in a fast, economical and accurate way.

-Mainstream adapter for orotracheal tube, on the bottom and on the top, for nasal cannulae with oral portion, aiming the collection of air exhaled through the mouth. As can be seen, the sensor is close to the airway Some of the revised studies (1,(18)(19) suggest the usefulness of this parameter for an initial and a rapid screening, both at hospital and outpatient levels, of those patients at high risk of suffering from some severe metabolic change. This indicates the potential of this parameter as a sentinel sign, capable of detecting those patients at highest risk, in order to quickly submit them to the necessary supplementary screening tests and administer an initial treatment as early and specific as possible. Some authors have already defined capnography as the sixth vital sign, with potential to improve risk stratification in the emergency settings (19) .
The objective of this review is to evaluate the usefulness of capnography for the detection of metabolic changes in spontaneous breathing patients, in the emergency and intensive care settings. Cochrane Library. The selection of articles was limited to all types of publication in English and Spanish over the last 10 years. Those references whose title and content did not meet the inclusion and exclusion criteria were excluded.

Methods
The inclusion criteria were that the article included capnography in the assessment of patients with potential metabolic changes, in its title or abstract; that the article assessed the consistency between the values obtained by capnography and the other parameters included in the blood acid-base balance; and that spontaneous breathing patients were included in the study. The exclusion criteria were that the study did not assess the correlation between the gasometric values of blood acid-base balance and the EtCO 2 values; that the objective of the study was to assess the correlation between arterial CO 2 partial pressure (PaCO 2 ) and EtCO 2 , only in chronic respiratory patients. In addition, these studies assessed the use of capnography only in patients submitted to invasive mechanical ventilation and only focused on transcutaneous capnography. Table 1 shows the distribution of the articles found, according to the different databases.  study methodology, but with uninteresting results for the study, 4 points if it was relevant for the methodology, results, conclusions and theoretical framework.
After completing the two phases of the bibliographical search, the same strategy was repeated by an expert in Documentation Science, using the descriptors and their Boolean combinations over the ten years and the language used in the databases, and the same results were found. Thus, the validity of this review was ensured.

Results
In the initial phase of this study, 22 articles were selected and 11 critical readings resulted after applying the inclusion and exclusion criteria. These 11 articles were scored according to the Likert scale (Table 2).
In the second phase of the guided search or snowball sampling, another nine articles were selected, which are presented in Table 2 focused on adults (70.59%), as described in Table 3.
The pathologies studied in the pediatric population were: 3 articles on the use of capnography in diabetic ketoacidosis (DKA) and 2 in acute gastroenteritis (AGE).
In the adult population, 3 articles were focused on patients cared for in emergency settings due to metabolic changes, 4 on dyspneic patients, 2 on septic/febrile patients, 1 on DKA and finally, 2 assessed the Mainstream and Sidestream systems. The sample sizes of the studies were very variable, ranging from 25 subjects, which was the smallest number of patients included (12) , to 1088 patients, which was the largest sample analyzed (19) . The sample size mean of all studies analyzed was 163.41 individuals, whose distribution can be observed in Table 3.
As for the studies from the secondary search, in one of them (21) , it was carried out a review on the use of capnography protocols in an outpatient service to diagnose septic patients. The other one (15)  Among the pediatric studies, one of them (23) found that no patient with EtCO 2 > 30mmHg had DKA  (11) , similar results were also obtained with the same type of pediatric patients, between EtCO 2 and PCO 2 (r=0.84, p<0.0001), and between EtCO 2 and

Discussion
Most of the studies show that capnography has proven to be a gold standard in the urgency and emergency settings, and its complementarity is It is noteworthy that all studies on the pediatric population, both aimed at the detection of DKA (11,23,26) and those performed in patients with AGE ( have been carried out on child population and are less invasive tests. These results are considered as paradoxical because the differential physiological gradient between EtCO 2 and venous CO 2 pressure (PvCO 2 ), should be greater than the gradient between EtCO 2 and PaCO 2 , as the mean difference between PaCO 2 and PvCO 2 is 6-8 mmHg (40mmHg PaCO 2 vs 48mmHg PvCO 2 ) (15)(16) . According to these studies (11,24) , EtCO 2 is a valid and reliable system for use in the pediatric population, and may even help to reduce costs, as it diminishes the blood tests, emphasizing that it is not possible to completely abolish the latter as reliable tests for confirmation of the results.
On the other hand, in the adult population, no correlation and/or concordance was found between the study variables, discouraging the use of this system to assess the patient's metabolic and/or ventilatory status, according to several studies (20,(27)(28)30) . The final diagnoses of the patients included in these studies (27)(28) were associated with chronic respiratory or cardiac diseases, which directly influences the physiology and the EtCO 2 values. However, a good correlation was found in previous studies (2,22)  with the use of a Mainstream system, which may also be related to the results of a previous study (22) that used a Mainstream system.
Having the sensor near the airway seems to reduce the chance of mixing atmospheric air, just as Sidestream systems tend to increase dead space through the aspiration tube. In fact, in the conclusions of a study (20) , it is suggested that the low correlation found in the results is due to the measuring systems and methods. In this sense, it can be noticed that in the results of another study (17) , which assessed three types of patients with different pathologies, all measurements were performed using a Mainstream and Microstream system, along with different cannula models, and a strong correlation was found. This was the strongest correlation found with the use of a Mainstream system, which presented a good correlation in the nonobese patients without OSAS since they had a better pulmonary function.
On the other hand, based on another study (30) with potentially septic patients, it is not possible to draw the same conclusions, since the final diagnostic of patients was not revealed, although patients with chronic respiratory disease were excluded. This study did not recommend the use of capnography as a tool for decision making, but it mentions the feasibility of its use for monitoring in the emergency services. This study also did not reveal the type of cannula used or the duration of EtCO 2 measurement, which makes its reproducibility difficult and may lead to measurement imprecisions.
Studies focused purely on the detection of metabolic changes in adults (3,18,30) , aim to ratify its practical utility as a tool for clinical decision making. A study (3) seems to show its real potential use as a predictive tool in emergency services as well as an indicator of acidosis or not. In another study (18) on patients with suspicion of sepsis, a better correlation with lactate levels was observed than in the previous study (30) , which may be because the sample in the last study (18)  for OTT was used. These authors (18) also assessed the correlation of EtCO 2 values with mortality and lactate, indicating their use to predict mortality and the presence of septic status in these patients.
In a later study (19), with a much extensive sample (n=1088), the same authors also found a strong correlation. In addition, they analyzed and compared the values of normal vital signs in relation to EtCO 2 , the latter parameter being the most predictive and consistent value to indicate mortality in the outpatient environment, hence they designated it as the sixth vital sign. In this later work (19)