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.

Descriptors:
Capnography; Metabolic Diseases; Acidosis; Alkalosis; Carbon Dioxide; Spontaneous Breathing.

RESUMO

Objetivo:

avaliar a utilidade da capnografia para a detecção de alterações metabólicas em pacientes com respiração espontânea, no contexto das emergências e dos cuidados intensivos.

Método:

pesquisa bibliográfica estruturada aprofundada, nas bases de dados EBSCOhost, Biblioteca Virtual em Saúde, PubMed, Cochrane Library, entre outras, identificando estudos que avaliavam a relação entre os valores da capnografia e as variáveis envolvidas no equilíbrio ácido-base sanguíneo.

Resultados:

foram levantados 19 estudos, dois eram revisões e 17 eram estudos observacionais. Em nove estudos, os valores capnográficos foram correlacionados com o dióxido de carbono (CO₂), em oito com o bicarbonato (HCO₃), em três com o lactato, e em quatro com o pH sanguíneo.

Conclusões:

na maioria dos estudos foi observada uma correlação adequada entre os valores capnográficos e os biomarcadores sanguíneos, sugerindo a utilidade deste parâmetro para a identificação de pacientes com risco de sofrer uma alteração metabólica grave, de uma forma rápida, econômica e precisa.

Descritores:
Capnografia; Doenças Metabólicas; Acidose; Alcalose; Dióxido de Carbono; Respiração Espontânea

RESUMEN

Objetivo:

explorar la utilidad de la capnografía para la detección de alteraciones metabólicas ante pacientes en respiración espontánea, en el ámbito de las emergencias y los cuidados críticos.

Método:

búsqueda bibliográfica estructurada en profundidad, en bases de datos EBSCOhost, Biblioteca Virtual de la Salud, PubMed, Cochrane Library, entre otras, identificando estudios que evaluaban la relación entre valores de la capnografía y variables implicadas en el equilibrio ácido-base sanguíneo.

Resultados:

se recopilaron 19 estudios, dos eran revisiones y 17 observacionales. En nueve estudios, se correlacionaron los valores capnográficos junto al dióxido de carbono (CO₂), en ocho con el bicarbonato (HCO₃), tres con el lactato, y cuatro con el pH sanguíneo.

Conclusiones:

la mayoría de estudios han obtenido una correlación adecuada entre los valores capnográficos y biomarcadores sanguíneos, sugiriendo la utilidad de este parámetro para la detección de pacientes en riesgo de padecer una alteración metabólica grave, de forma rápida, económica y precisa.

Descriptores:
Capnografía; Enfermedades Metabólicas; Acidosis; Alcalosis; Dióxido de Carbono; Respiración Espontánea

Introduction

In the emergency services, to diagnose and evaluate the treatments administered to patients with pathologies as diverse as metabolic or electrolytic changes, hypoxemia and hypercapnia, an arterial blood gas (ABG) test or a venous blood gas (VBG) test is required to assess the oxygenation, ventilation and metabolic status¹1 Pishbin E, Ahmadi GD, Sharifi MD, Deloei MT, Shamloo AS, Reihani H. The correlation between end-tidal carbon dioxide and arterial blood gas parameters in patients evaluated for metabolic acid-base disorders. Electron Physician. [Internet]. [Access Jul 20, 2015];7(3):1095-101. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=26388974&site=ehost-live
http://search.ebscohost.com/login.aspx?d... . On the other hand, blood gas analysis is usually not a supplementary test available in outpatient emergency services and in many hospital emergency services, and it is unusual the presence of specific equipments, which requires sending a sample to the laboratory, with a consequent delay in results²2 Yosefy C, Hay E, Nasri Y, Magen E, Reisin L. End tidal carbon dioxide as a predictor of the arterial PCO2 in the emergency department setting. Emerg Med J EMJ. [Internet]. 2004 Sep [Access Jul 20, 2015];21(5):557-9. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=15333528&site=ehost-live
http://search.ebscohost.com/login.aspx?d... .

The assessment of blood acid-base balance is performed using aggressive techniques, which require material resources, team time and are not free of potential complications¹1 Pishbin E, Ahmadi GD, Sharifi MD, Deloei MT, Shamloo AS, Reihani H. The correlation between end-tidal carbon dioxide and arterial blood gas parameters in patients evaluated for metabolic acid-base disorders. Electron Physician. [Internet]. [Access Jul 20, 2015];7(3):1095-101. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=26388974&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,33 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... . Capnography is an alternative method that can help assess the patients' metabolic status in a noninvasive way, in fact, it has been used for years as a quality standard in patient care monitoring in a variety of heathcare areas, including anesthesia and resuscitation, intensive care and emergencies⁴4 Cooper CJ, Kraatz JJ, Kubiak DS, Kessel JW, Barnes SL. Utility of Prehospital Quantitative End Tidal CO2? Prehosp Disaster Med. [Internet]. 2013 [Access Jul 11, 2015];28(2):87-93. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23343590
http://www.ncbi.nlm.nih.gov/pubmed/23343...

5 Manifold CA, Davids N, Villers LC, Wampler DA. Capnography for the Nonintubated Patient in the Emergency Setting. J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];45(4):626-32. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0736467913005088
http://linkinghub.elsevier.com/retrieve/... ^-66 Whitaker DK. Time for capnography - everywhere. Anaesthesia. [Internet]. 2011 [Access Jul 10, 2015];66(7): 544-9.. Through it, a supplementary monitoring to pulse oximetry is achieved, as capnography provides direct and immediate information on ventilation, whereas pulse oximetry only quantifies oxygenation⁷7 Díez-Picazo LD, Barrado-Muñoz L, Blanco-Hermo P, Barroso-Matilla S, Espinosa Ramírez S. La capnografía en los servicios de emergencia médica. Semer - Med Fam. [Internet]. 2009 [Access Jul 20, 2015];35(3):138-43. Available from: http://www.elsevier.es/es-revista-semergen-medicina-familia-40-articulo-la-capnografia-los-servicios-emergencia-13135238
http://www.elsevier.es/es-revista-semerg... . With the use of capnography, it is possible to know objectively the patients' metabolic status¹1 Pishbin E, Ahmadi GD, Sharifi MD, Deloei MT, Shamloo AS, Reihani H. The correlation between end-tidal carbon dioxide and arterial blood gas parameters in patients evaluated for metabolic acid-base disorders. Electron Physician. [Internet]. [Access Jul 20, 2015];7(3):1095-101. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=26388974&site=ehost-live
http://search.ebscohost.com/login.aspx?d...

2 Yosefy C, Hay E, Nasri Y, Magen E, Reisin L. End tidal carbon dioxide as a predictor of the arterial PCO2 in the emergency department setting. Emerg Med J EMJ. [Internet]. 2004 Sep [Access Jul 20, 2015];21(5):557-9. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=15333528&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-33 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , correct installation of orotracheal tube (OTT) in the bronchial tree, quality and effectiveness of cardiopulmonary resuscitation (CPR) maneuvers, restoration of spontaneous circulation during CPR, monitoring of invasive and non-invasive mechanical ventilation and spontaneous ventilation⁸8 Kupnik D, Skok P. Capnometry in the prehospital setting: are we using its potential? Emerg Med J. 2007 Sep;24(9):614-7.

9 Deakin CD, Nolan JP, Soar J, Sunde K, Koster RW, Smith GB, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation. [Internet]. 2010 [Access Jul 20, 2015];81(10):1305-52. Available from: http://www.resuscitationjournal.com/article/S0300957210004430/fulltext
http://www.resuscitationjournal.com/arti... ^-1010 Díez-Picazo LD, Matilla SB, Córdoba RC, Muñoz AG. La monitorización capnográfica en la parada cardiaca extrahospitalaria. Emergencias Rev la Soc Española Med Urgencias y Emergencias. Saned; 2010;22(5):345-8..

Several revised articles suggest the usefulness of capnography for this purpose, given a good correlation between CO₂ values at the end of expiration (known as end-tidal CO₂ or EtCO₂) and other variables involved in the binomial blood acid-base¹1 Pishbin E, Ahmadi GD, Sharifi MD, Deloei MT, Shamloo AS, Reihani H. The correlation between end-tidal carbon dioxide and arterial blood gas parameters in patients evaluated for metabolic acid-base disorders. Electron Physician. [Internet]. [Access Jul 20, 2015];7(3):1095-101. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=26388974&site=ehost-live
http://search.ebscohost.com/login.aspx?d...

2 Yosefy C, Hay E, Nasri Y, Magen E, Reisin L. End tidal carbon dioxide as a predictor of the arterial PCO2 in the emergency department setting. Emerg Med J EMJ. [Internet]. 2004 Sep [Access Jul 20, 2015];21(5):557-9. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=15333528&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-33 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,55 Manifold CA, Davids N, Villers LC, Wampler DA. Capnography for the Nonintubated Patient in the Emergency Setting. J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];45(4):626-32. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0736467913005088
http://linkinghub.elsevier.com/retrieve/... ^,1010 Díez-Picazo LD, Matilla SB, Córdoba RC, Muñoz AG. La monitorización capnográfica en la parada cardiaca extrahospitalaria. Emergencias Rev la Soc Española Med Urgencias y Emergencias. Saned; 2010;22(5):345-8.

11 Agus MSD, Alexander JL, Mantell P a. Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with diabetic ketoacidosis. Pediatr Diabetes. [Internet]. 2006 [Access Jul 20, 2015];7(4):196-200. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=16911005&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-1212 Solana Garcia MJ, Lopez Lopez R, Adrian Gutierrez J, Penalba Citores A, Guerrero Soler M, Maranon Pardillo R. [Use of capnography in acute gastroenteritis]. An Pediatr. 2008 [Access Jul 20, 2015];68(4):342-5.. For more than a decade, emergency medical services (EMS) have long been equipped with portable capnographs, according to the last three published editions of the international guidelines on CPR⁹9 Deakin CD, Nolan JP, Soar J, Sunde K, Koster RW, Smith GB, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation. [Internet]. 2010 [Access Jul 20, 2015];81(10):1305-52. Available from: http://www.resuscitationjournal.com/article/S0300957210004430/fulltext
http://www.resuscitationjournal.com/arti... ^,1313 Part 6: Advanced Cardiovascular Life Support : Section 1: Introduction to ACLS 2000: Overview of Recommended Changes in ACLS From the Guidelines 2000 Conference. Circulation. [Internet]. 2000 [Access Jul 20, 2015];102(Supplement 1):I-86-I-89. Available from: http://circ.ahajournals.org/cgi/content/long/102/suppl_1/I-86
http://circ.ahajournals.org/cgi/content/... ^-1414 Soar J, Nolan JP, Böttiger BW, Perkins GD, Lott C, Carli P, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support. Resuscitation. [Internet]. 2015 [Access Jul 20, 2016];95:100-47. Available from: http://www.sciencedirect.com/science/article/pii/S0300957215003287
http://www.sciencedirect.com/science/art... , so that capnographs are generally included in the defibrillator-monitors⁷7 Díez-Picazo LD, Barrado-Muñoz L, Blanco-Hermo P, Barroso-Matilla S, Espinosa Ramírez S. La capnografía en los servicios de emergencia médica. Semer - Med Fam. [Internet]. 2009 [Access Jul 20, 2015];35(3):138-43. Available from: http://www.elsevier.es/es-revista-semergen-medicina-familia-40-articulo-la-capnografia-los-servicios-emergencia-13135238
http://www.elsevier.es/es-revista-semerg... . Therefore, it is interesting to know the potential utility of this parameter to detect these changes, as well as to analyze the variables that potentially influence the EtCO₂ measurements in spontaneous breathing patients.

The types of capnography infrared sensors used in the current monitors are mainly divided into two types according to their location: mainstream, whose sensor is located near the airway (Figure 1); sidestream, whose sensor is on the monitor, away from the airway, and through a cannula, a small volume of the exhaled air is continuously aspirated (between 100-150ml/min) (Figure 2) and passed into a sensor located on the monitor. In addition, currently, the Microstream technology is also available, a version of the Sidestream that requires even less sample, about 50 ml/min⁷7 Díez-Picazo LD, Barrado-Muñoz L, Blanco-Hermo P, Barroso-Matilla S, Espinosa Ramírez S. La capnografía en los servicios de emergencia médica. Semer - Med Fam. [Internet]. 2009 [Access Jul 20, 2015];35(3):138-43. Available from: http://www.elsevier.es/es-revista-semergen-medicina-familia-40-articulo-la-capnografia-los-servicios-emergencia-13135238
http://www.elsevier.es/es-revista-semerg... ^,1515 Casey G. Capnography: monitoring CO2. [Internet]. Kai Tiaki Nurs. [Internet]. 2015 [Access Jul 20, 2015];21(9):20-45p. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=110468564&site=ehost-live
http://search.ebscohost.com/login.aspx?d...

16 Restrepo RD, Nuccio P, Spratt G, Waugh J. Current applications of capnography in non-intubated patients. Expert Rev Respir Med. [Internet].2014 [Access Jul 20, 2015];8(5):629-39. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=25020234&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-1717 Kasuya Y, Akca O, Sessler DI, Ozaki M, Komatsu R. Accuracy of postoperative end-tidal Pco2 measurements with mainstream and sidestream capnography in non-obese patients and in obese patients with and without obstructive sleep apnea. Anesthesiology. 2009;11(3):609-15.. All systems are supplied with adapters for OTT and nasal or oro-nasal cannulas.

Some of the revised studies¹1 Pishbin E, Ahmadi GD, Sharifi MD, Deloei MT, Shamloo AS, Reihani H. The correlation between end-tidal carbon dioxide and arterial blood gas parameters in patients evaluated for metabolic acid-base disorders. Electron Physician. [Internet]. [Access Jul 20, 2015];7(3):1095-101. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=26388974&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,1818 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-1919 Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. [Internet]. 2014 [Access Jul 20, 2015];32(2):160-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24332900
http://www.ncbi.nlm.nih.gov/pubmed/24332... 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 settings¹⁹19 Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. [Internet]. 2014 [Access Jul 20, 2015];32(2):160-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24332900
http://www.ncbi.nlm.nih.gov/pubmed/24332... .

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.

Methods

An in-depth and structured bibliographical research was carried out from December 2015 to January 2016, in two phases.

Firstly, from the question and objectives of the study, it was obtained the keywords that were translated into documentary language or descriptors on Health Sciences Descriptors (DeCS). The entries capnography and metabolic diseases were selected as root or primary descriptors, acidosis and alkalosis as secondary, and their combination with the Boolean operators was set as follows: (capnography[MeSH]) AND (metabolic diseases[MeSH] OR acidosis[MeSH] OR alkalosis[MeSH]).

Considering the areas of knowledge, the following databases were selected for the collection of primary sources: EBSCOhost [which included the databases: MEDLINE Complete, Cumulative Index for Nursing and Allied Health Literature (CINAHL) Complete, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register (CMR), NHS Economic Evaluation Database (EED), Health Technology Assessments (HTA), Library Information Science & Technology Abstracts (LISTA), Virtual Health Library (VHL), PubMed, Spanish Medical Index (IME), Spanish Bibliographic Index of Health Sciences (IBECS), Latin American Literature in Health Sciences (LILACS) and 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.

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 EtCO₂ values; that the objective of the study was to assess the correlation between arterial CO₂ partial pressure (PaCO₂) and EtCO₂, 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.

In the second phase, a specific research was carried out in order to complete the selection of articles. For this purpuse, some of the citations that the authors of the selected studies used and were relevant for the present study were located and incorporated, as shown in Tables 1 and 2.

The structured search was performed in pairs as well as the final decision to include or exclude a certain study. In preparing of this article, a worksheet was used for the elaboration of a structured summary about each consulted article (introduction, justification, objectives, type of study design, year of completion, sample size, methodology, main results, discussion, limitations, conclusions, observations and recommended bibliography). In this worksheet, the degree of adequacy of each article was assessed using a 4-point Likert scale, according to the criteria and methodological quality of the results presented. The Likert scale scoring was as follows: 1 point if the article was not relevant for the study objectives, 2 points if it was relevant for the justification of theoretical framework of the study, but with poor methodological quality, 3 points if it was relevant for the 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, together with the initial search and scoring obtained according to the Likert scale. Two of the included articles¹⁷17 Kasuya Y, Akca O, Sessler DI, Ozaki M, Komatsu R. Accuracy of postoperative end-tidal Pco2 measurements with mainstream and sidestream capnography in non-obese patients and in obese patients with and without obstructive sleep apnea. Anesthesiology. 2009;11(3):609-15.^,2020 Pekdemir M, Cinar O, Yilmaz S, Yaka E, Yuksel M. Disparity between mainstream and sidestream end-tidal carbon dioxide values and arterial carbon dioxide levels. Respir Care. 2013 Jul;58(7):1152-6. had been selected because they analyzed variables such as the correlation between the measuring devices, according to the type of sensor used, Mainstream or Sidestream, which seemed to be important factors in evaluating the possible variables involved in the parametrization of capnography in spontaneous breathing.

Of the 19 articles finally selected, 17 were from the primary search (89.4%) and two from the secondary search (10.53%). Regarding the distribution according to the study design, 15 were prospective observational studies (88.23%) and two were retrospective observational studies (11.76%), of which five were focused on pediatric patients (29.41%) and the remaining 12 ones were 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 included¹²12 Solana Garcia MJ, Lopez Lopez R, Adrian Gutierrez J, Penalba Citores A, Guerrero Soler M, Maranon Pardillo R. [Use of capnography in acute gastroenteritis]. An Pediatr. 2008 [Access Jul 20, 2015];68(4):342-5., to 1088 patients, which was the largest sample analyzed¹⁹19 Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. [Internet]. 2014 [Access Jul 20, 2015];32(2):160-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24332900
http://www.ncbi.nlm.nih.gov/pubmed/24332... . 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 them²¹21 Hunter CL. Use End-tidal Carbon Dioxide to Diagnose Sepsis. J Emergency Med Services. [Internet]. [Access Jan 18, 2016]. Available from: http://www.jems.com/articles/print/volume-39/issue-3/features/use-end-tidal-carbon-dioxide-to-diagnose-sepsis.html
http://www.jems.com/articles/print/volum... , it was carried out a review on the use of capnography protocols in an outpatient service to diagnose septic patients. The other one¹⁵15 Casey G. Capnography: monitoring CO2. [Internet]. Kai Tiaki Nurs. [Internet]. 2015 [Access Jul 20, 2015];21(9):20-45p. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=110468564&site=ehost-live
http://search.ebscohost.com/login.aspx?d... is an article on nursing continuing education and updating of knowledge about the different fields of application of capnography.

Regarding the materials used for parameterization of EtCO₂, it was found four studies that used simple nasal cannulas (Nc); five used nasal cannulas with oral portion (Nco) for the detection of the air exhaled through the mouth; two used adapters of OTT, through which patients with ventilation breathed; three studies did not specify the type of cannula used and; three studies used different cannulae or adapters, according to the type of capnograph used¹⁷17 Kasuya Y, Akca O, Sessler DI, Ozaki M, Komatsu R. Accuracy of postoperative end-tidal Pco2 measurements with mainstream and sidestream capnography in non-obese patients and in obese patients with and without obstructive sleep apnea. Anesthesiology. 2009;11(3):609-15.^-1818 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,2020 Pekdemir M, Cinar O, Yilmaz S, Yaka E, Yuksel M. Disparity between mainstream and sidestream end-tidal carbon dioxide values and arterial carbon dioxide levels. Respir Care. 2013 Jul;58(7):1152-6..

As for the capnographs used according to their technology, 12 used Sidestream capnographs, out of these, seven were of the Microstream type. Only one study exclusively used the Mainstream²²22 Cinar O, Acar YA, Arziman İ, Kilic E, Eyi YE, Ocal R. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide level of patients with acute dyspnea in ED. Am J Emerg Med. [Internet]. 2012 [Access May 18, 2016];30(2):358-61. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=2011450999&site=ehost-live
http://search.ebscohost.com/login.aspx?d... system, another one specified the type of instrument used³3 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , but did not prove its technology since the manufacturer's specifications were not revealed, and three used two systems (Mainstream and Microstream) to compare their results¹⁷17 Kasuya Y, Akca O, Sessler DI, Ozaki M, Komatsu R. Accuracy of postoperative end-tidal Pco2 measurements with mainstream and sidestream capnography in non-obese patients and in obese patients with and without obstructive sleep apnea. Anesthesiology. 2009;11(3):609-15.^-1818 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,2020 Pekdemir M, Cinar O, Yilmaz S, Yaka E, Yuksel M. Disparity between mainstream and sidestream end-tidal carbon dioxide values and arterial carbon dioxide levels. Respir Care. 2013 Jul;58(7):1152-6..

The list of capnographs used is shown in Table 3. In total, 16 capnographs of different brands and models have been used, and the only capnograph used in three studies was the Microcap, Oridion Capnography Inc., Needham, MA. Nine of these articles do not specify the duration of the capnography measurement and eight do. Of these, one performs a continuous monitoring, five perform monitoring for one minute or more, and two measure the EtCO₂ values after 3-5 ventilations.

Regarding the correlation between the EtCO₂ values and the values of the variables involved in blood acid-base balance, six of the studies compared these values using venous samples, the remaining 11 studies used arterial blood samples. Nine studies used the Pearson correlation coefficient to analyze the association with PCO₂, eight with HCO₃, three with lactate, four with blood pH, one with the Sequential Organ Failure Assessment (SOFA). In addition to linear correlation, six studies also analyzed the concordance between the measurements and the results by means of the Bland-Altman Formula (FBA).

Among the pediatric studies, one of them²³23 Gilhotra Y, Porter P. Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography. J Paediatr Child Health. 2007 Oct;43(10):677-80. found that no patient with EtCO₂ > 30mmHg had DKA (sensitivity of 1.0, specificity of 0.86), correlation between EtCO₂ and HCO₃ ^¯ (r=0.72). In this study, these findings can be compared with those of another study²⁴24 Nagler J, Wright RO, Krauss B, RO W, Krauss B, Wright RO, et al. End-tidal carbon dioxide as a measure of acidosis among children with gastroenteritis. Pediatrics [Internet]. Am Acad Pediatrics. [Internet]. 2006 [Access Jul 15, 2015];118(1):260-7. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=106343444&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , which observed that EtCO₂> 34mmHg is out of range in relation to values of HCO₃¯ ≤15mmHg (100% sensitivity), whereas EtCO₂ ≤ 31mmHg showed 96% specificity in detecting acidosis in pediatric patients with AGE; indicating a significant correlation between EtCO₂ and HCO₃ (r=0.80, p<0.0001).

In their studies²⁵25 Solana García MJ, López López R, Adrián Gutiérrez J, Peñalba Cítores A, Guerrero Soler M, Marañón Pardillo R. Use of capnography in acute gastroenteritis. An Pediatr (Barc). 2008 [Access Apr 17, 2016];68(4):342-5. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=18394377&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , other authors monitored children with AGE and dehydration as well as the evolution of the treatment by capnography when intravenous rehydration was initiated, and they observed an improvement in the correlation between the initial values of EtCO₂ and HCO₃ ^¯ (r=0.61, p<0.0001), and after treatment initiation (r=0.75, p<0.0001). Another study²⁶26 Garcia E, Abramo TJ, Okada P, Guzman DD, Reisch JS WR. Ovid: Capnometry for noninvasive continuous monitoring of metabolic status in pediatric diabetic ketoacidosis. [Internet]. Crit Care Med. [Internet] 2003 [Access Oct 9, 2016];31(10):2539-43. Available from: http://ovidsp.uk.ovid.com/sp-3.17.0a/ovidweb.cgi?&S=BDONPDHIOGHFJMFMFNJKNEBGCHHCAA00&Link+Set=S.sh.22%7c1%7csl_10
http://ovidsp.uk.ovid.com/sp-3.17.0a/ovi... also found a good correlation between EtCO₂ and pH (r=0.88, p<0.0001) and between EtCO₂ and PCO₂ (r=0.92, p<0.0001) during continuous monitoring of patients with DKA and, by means of FBA, the limits of agreement between EtCO₂ and PCO₂ were defined as 0.8 ± 4.2 mmHg. In a later study¹¹11 Agus MSD, Alexander JL, Mantell P a. Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with diabetic ketoacidosis. Pediatr Diabetes. [Internet]. 2006 [Access Jul 20, 2015];7(4):196-200. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=16911005&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , similar results were also obtained with the same type of pediatric patients, between EtCO₂ and PCO₂ (r=0.84, p<0.0001), and between EtCO₂ and HCO₃ ^¯ (r=0.84, p<0.0001). They also assessed the concordance between EtCO₂ and HCO₃ ^¯ by using FBA and the result was -0.51 ± 2.31 mmHg, and between EtCO₂ and PCO₂ was -0.29 ± 4.18 mmHg.

In studies targeting adults grouped according to the reason of the consultation, the following results were found.

In patients with dyspnea, one study²⁷27 Jabre P, Jacob L, Auger H, Jaulin C, Monribot M, Aurore A, et al. Capnography monitoring in nonintubated patients with respiratory distress. Am J Emerg Med. [Internet]. 2009 [Access Oct 9, 2016];27(9):1056-9. Available from: http://www.sciencedirect.com/science/article/pii/S0735675708006141
http://www.sciencedirect.com/science/art... analyzed the concordance between EtCO₂ and PaCO₂, with a mean deviation between the two parameters of 12mmHg. The correlation between the EtCO₂-PaCO₂ gradient and the respiratory rate, obtained by FBA, was weak (r=0.21; p<0.014); however, the authors did not analyze the direct correlation between EtCO₂ and PaCO₂. On the other hand, in another study²⁸28 Delerme S, Freund Y, Renault R, Devilliers C, Castro S, Chopin S, et al. Concordance between capnography and capnia in adults admitted for acute dyspnea in an ED. Am J Emerg Med. [Internet]. 2010 [Access Oct 9, 2016];28(6):711-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=cgh&AN=CN-00752739&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , a good correlation was found between EtCO₂ and PaCO₂, but the concordance between the two values, by means of FBA, was weak, ranging from -10 mmHg to +26 mmHg. It should be emphasized the results of another previous study²2 Yosefy C, Hay E, Nasri Y, Magen E, Reisin L. End tidal carbon dioxide as a predictor of the arterial PCO2 in the emergency department setting. Emerg Med J EMJ. [Internet]. 2004 Sep [Access Jul 20, 2015];21(5):557-9. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=15333528&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , that, on the contrary, found a strong correlation between EtCO₂ and PaCO₂ (r=0.792). Similarly, another study²²22 Cinar O, Acar YA, Arziman İ, Kilic E, Eyi YE, Ocal R. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide level of patients with acute dyspnea in ED. Am J Emerg Med. [Internet]. 2012 [Access May 18, 2016];30(2):358-61. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=2011450999&site=ehost-live
http://search.ebscohost.com/login.aspx?d... found a strong correlation between EtCO₂ and PaCO₂ (r=0.911, p<0.001) and also a good concordance, by means of FBA, 0.5 ± 5 mmHg (95% CI, -1.3165-0.2680).

Among those studies comparing different capnography systems, it was observed a study²⁰20 Pekdemir M, Cinar O, Yilmaz S, Yaka E, Yuksel M. Disparity between mainstream and sidestream end-tidal carbon dioxide values and arterial carbon dioxide levels. Respir Care. 2013 Jul;58(7):1152-6. that found: using the Mainstream system, a moderate correlation between EtCO₂ and PaCO₂ (r=0.55, p<0.001), by FBA, from -0.6 mmHg to 25.5 mmHg. With the use of the Microstream system, the correlation between EtCO₂ and PaCO₂ was r=0.41 (p<0.001), by FBA, ranging from -5.4 mmHg to 24.7 mmHg. In another study¹⁷17 Kasuya Y, Akca O, Sessler DI, Ozaki M, Komatsu R. Accuracy of postoperative end-tidal Pco2 measurements with mainstream and sidestream capnography in non-obese patients and in obese patients with and without obstructive sleep apnea. Anesthesiology. 2009;11(3):609-15. conducted with non-obese postoperative patients, obese with and without obstructive sleep apnea syndrome (OSAS); comparing two measuring instruments and three different cannulae, the following results were obtained in the correlation between EtCO₂ and PaCO₂: Non-obese: Mainstream-Nco (r=0.91, p<0.001), Microstream-Nco (r=0.85, p<0.001), Microstream-Nc (r=0.72, p<0.001). Obese patients without OSAS: Mainstream-Nco (r=0.91, p<0.001), Microsteam-Nco (r=0.7, p<0.001), Microstream-Nc (r=0.65, p<0.001). Obese patients with OSAS: Mainstream-Nco (r=0.76, p<0.001), Microstream-Nco (r=0.72, p<0.001), Microstream-Nc (r=0.39, p<0.001).

Among those studies focused directly on metabolic changes, it was found a study³3 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... that is the only one aiming at the detection of DKA in adults. In such a study, it was obtained a moderate correlation between EtCO₂ and PaCO₂ (0.572, p>0.0001) and a strong correlation between EtCO₂ and HCO₃¯ (r=0.730, p>0.0001), indicating that values of EtCO₂ > 24.5mmHg were out of the interval for DKA, with sensitivity of 0.90 and specificity of 0.90. On the other hand, in another study²⁹29 Kartal M, Eray O, Rinnert S, Goksu E, Bektas F, Eken C. ETCO2: a predictive tool for excluding metabolic disturbances in nonintubated patients. Am J Emerg Med [Internet]. 2011 [Access Oct 9, 2016];29(1):65-9. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=20825776&site=ehost-live
http://search.ebscohost.com/login.aspx?d... that found a moderate correlation between EtCO₂ and HCO₃ (r=0.506), it was obtained values of EtCO₂ ≤ 25, with a specificity of 84% for acidosis in its sample, and EtCO₂ ≥37mmHg, with 100% sensitivity for absence of metabolic acidosis. Still, in another previous study³⁰30 McGillicuddy DC, Tang A, Cataldo L, Gusev J, Shapiro NI, DC M, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA scores and lactic acidosis. Intern Emerg Med [Internet]. 2009 2003 [Access Oct 9, 2016];4(1):41-44. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=105639755&lang=es&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , a weak inverse correlation was obtained between EtCO₂ and SOFA (r= -0.35, p<0.01) and between EtCO₂ and lactate (r= -0.35, p<0.01) in febrile and potentially septic patients. However, in a later study¹⁸18 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , a moderate inverse correlation was found between EtCO₂ and lactate, according to the septic status: in patients with sepsis (r= -0.421, p<0.001), severe sepsis (r= -0.597, p<0.001), and septic shock (r= -0.482, p<0.011). They studied the relationship between EtCO₂ values and mortality, obtaining in those who died, a mean EtCO₂ value of 26mmHg (95%CI, 21-30); and for those who survived, a mean EtCO₂ value of 33mmHg (95%CI, 31-34). In another study of the same authors mentioned above¹⁹19 Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. [Internet]. 2014 [Access Jul 20, 2015];32(2):160-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24332900
http://www.ncbi.nlm.nih.gov/pubmed/24332... , aiming at the detection of septic patients, it was observed a moderate correlation between EtCO₂ and HCO₃¯ (r=0.429; p<0.001), as well as between EtCO₂ and lactate (r= -0.376, p<0.001), which was only detected in 89 patients (n=201). In this case, the mean EtCO₂ value in patients who survived was 34mmHg and the mean EtCO₂ value in those who died was 25mmHg. Finally, there are the results of the last published article¹1 Pishbin E, Ahmadi GD, Sharifi MD, Deloei MT, Shamloo AS, Reihani H. The correlation between end-tidal carbon dioxide and arterial blood gas parameters in patients evaluated for metabolic acid-base disorders. Electron Physician. [Internet]. [Access Jul 20, 2015];7(3):1095-101. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=26388974&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , which found a strong correlation between EtCO₂ and HCO₃¯ (r=0.869, p<0.06), a weak correlation between EtCO₂ and pH (r=0.795, p<0.001), and a weak correlation between EtCO₂ and base excess by ABG analysis (r=0.346; p<0.006).

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 evidenced along with pulse oximetry, in the monitoring of patients' breathing, circulation and metabolism. In individuals with normal lung function, a 2-5 mmHg gradient difference between EtCO₂ and PaCO₂ is accepted regardless of age¹⁶16 Restrepo RD, Nuccio P, Spratt G, Waugh J. Current applications of capnography in non-intubated patients. Expert Rev Respir Med. [Internet].2014 [Access Jul 20, 2015];8(5):629-39. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=25020234&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,3131 Kodali BS. Capnography outside the operating rooms. Anesthesiology. [Internet]. 2013 [Access Oct 9, 2016]118(1):192-201. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=108088654&lang=es&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-3232 Soleimanpour H, Gholipouri C, Samad EJ Golzari FR, Sabahi M. Capnography in the Emergency Department [Internet]. Emergency Med. 2012. Available from: http://www.omicsgroup.org/journals/capnography-in-the-emergency-department -2165-7548.1000e123.pdf
http://www.omicsgroup.org/journals/capno... . The vast majority of the analyzed studies from the primary search showed a high correlation between the capnography values and the blood values of PCO₂ and/or HCO₃ ^¯.

It is noteworthy that all studies on the pediatric population, both aimed at the detection of DKA¹¹11 Agus MSD, Alexander JL, Mantell P a. Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with diabetic ketoacidosis. Pediatr Diabetes. [Internet]. 2006 [Access Jul 20, 2015];7(4):196-200. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=16911005&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,2323 Gilhotra Y, Porter P. Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography. J Paediatr Child Health. 2007 Oct;43(10):677-80.^,2626 Garcia E, Abramo TJ, Okada P, Guzman DD, Reisch JS WR. Ovid: Capnometry for noninvasive continuous monitoring of metabolic status in pediatric diabetic ketoacidosis. [Internet]. Crit Care Med. [Internet] 2003 [Access Oct 9, 2016];31(10):2539-43. Available from: http://ovidsp.uk.ovid.com/sp-3.17.0a/ovidweb.cgi?&S=BDONPDHIOGHFJMFMFNJKNEBGCHHCAA00&Link+Set=S.sh.22%7c1%7csl_10
http://ovidsp.uk.ovid.com/sp-3.17.0a/ovi... and those performed in patients with AGE²⁴24 Nagler J, Wright RO, Krauss B, RO W, Krauss B, Wright RO, et al. End-tidal carbon dioxide as a measure of acidosis among children with gastroenteritis. Pediatrics [Internet]. Am Acad Pediatrics. [Internet]. 2006 [Access Jul 15, 2015];118(1):260-7. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=106343444&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-2525 Solana García MJ, López López R, Adrián Gutiérrez J, Peñalba Cítores A, Guerrero Soler M, Marañón Pardillo R. Use of capnography in acute gastroenteritis. An Pediatr (Barc). 2008 [Access Apr 17, 2016];68(4):342-5. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=18394377&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , show a strong correlation between the EtCO₂ values and PCO₂ or HCO₃ ^¯. These studies have all been performed on venous samples, which is consistent because they have been carried out on child population and are less invasive tests.

These results are considered as paradoxical because the differential physiological gradient between EtCO₂ and venous CO₂ pressure (PvCO₂), should be greater than the gradient between EtCO₂ and PaCO₂, as the mean difference between PaCO₂ and PvCO₂ is 6-8 mmHg (40mmHg PaCO₂ vs 48mmHg PvCO₂)¹⁵15 Casey G. Capnography: monitoring CO2. [Internet]. Kai Tiaki Nurs. [Internet]. 2015 [Access Jul 20, 2015];21(9):20-45p. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=110468564&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^-1616 Restrepo RD, Nuccio P, Spratt G, Waugh J. Current applications of capnography in non-intubated patients. Expert Rev Respir Med. [Internet].2014 [Access Jul 20, 2015];8(5):629-39. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=25020234&site=ehost-live
http://search.ebscohost.com/login.aspx?d... . According to these studies¹¹11 Agus MSD, Alexander JL, Mantell P a. Continuous non-invasive end-tidal CO2 monitoring in pediatric inpatients with diabetic ketoacidosis. Pediatr Diabetes. [Internet]. 2006 [Access Jul 20, 2015];7(4):196-200. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=16911005&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,2424 Nagler J, Wright RO, Krauss B, RO W, Krauss B, Wright RO, et al. End-tidal carbon dioxide as a measure of acidosis among children with gastroenteritis. Pediatrics [Internet]. Am Acad Pediatrics. [Internet]. 2006 [Access Jul 15, 2015];118(1):260-7. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=106343444&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , EtCO₂ 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 studies²⁰20 Pekdemir M, Cinar O, Yilmaz S, Yaka E, Yuksel M. Disparity between mainstream and sidestream end-tidal carbon dioxide values and arterial carbon dioxide levels. Respir Care. 2013 Jul;58(7):1152-6.^,2727 Jabre P, Jacob L, Auger H, Jaulin C, Monribot M, Aurore A, et al. Capnography monitoring in nonintubated patients with respiratory distress. Am J Emerg Med. [Internet]. 2009 [Access Oct 9, 2016];27(9):1056-9. Available from: http://www.sciencedirect.com/science/article/pii/S0735675708006141
http://www.sciencedirect.com/science/art... ^-2828 Delerme S, Freund Y, Renault R, Devilliers C, Castro S, Chopin S, et al. Concordance between capnography and capnia in adults admitted for acute dyspnea in an ED. Am J Emerg Med. [Internet]. 2010 [Access Oct 9, 2016];28(6):711-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=cgh&AN=CN-00752739&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,3030 McGillicuddy DC, Tang A, Cataldo L, Gusev J, Shapiro NI, DC M, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA scores and lactic acidosis. Intern Emerg Med [Internet]. 2009 2003 [Access Oct 9, 2016];4(1):41-44. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=105639755&lang=es&site=ehost-live
http://search.ebscohost.com/login.aspx?d... . The final diagnoses of the patients included in these studies²⁷27 Jabre P, Jacob L, Auger H, Jaulin C, Monribot M, Aurore A, et al. Capnography monitoring in nonintubated patients with respiratory distress. Am J Emerg Med. [Internet]. 2009 [Access Oct 9, 2016];27(9):1056-9. Available from: http://www.sciencedirect.com/science/article/pii/S0735675708006141
http://www.sciencedirect.com/science/art... ^-2828 Delerme S, Freund Y, Renault R, Devilliers C, Castro S, Chopin S, et al. Concordance between capnography and capnia in adults admitted for acute dyspnea in an ED. Am J Emerg Med. [Internet]. 2010 [Access Oct 9, 2016];28(6):711-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=cgh&AN=CN-00752739&site=ehost-live
http://search.ebscohost.com/login.aspx?d... were associated with chronic respiratory or cardiac diseases, which directly influences the physiology and the EtCO₂ values. However, a good correlation was found in previous studies²2 Yosefy C, Hay E, Nasri Y, Magen E, Reisin L. End tidal carbon dioxide as a predictor of the arterial PCO2 in the emergency department setting. Emerg Med J EMJ. [Internet]. 2004 Sep [Access Jul 20, 2015];21(5):557-9. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=15333528&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,2222 Cinar O, Acar YA, Arziman İ, Kilic E, Eyi YE, Ocal R. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide level of patients with acute dyspnea in ED. Am J Emerg Med. [Internet]. 2012 [Access May 18, 2016];30(2):358-61. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=2011450999&site=ehost-live
http://search.ebscohost.com/login.aspx?d... with similar distribution of pathologies.

Special attention should be given to the results of one of the studies²⁰20 Pekdemir M, Cinar O, Yilmaz S, Yaka E, Yuksel M. Disparity between mainstream and sidestream end-tidal carbon dioxide values and arterial carbon dioxide levels. Respir Care. 2013 Jul;58(7):1152-6., in which patients with dyspnea treated in an emergency service were evaluated, including a group of individuals without this respiratory disease in the sample, in order to reduce the bias, according to the variables and measuring instruments. These authors found a moderate correlation between EtCO₂ and PaCO₂, despite of using a Microstream and Mainstream system, indicating a good correlation between the measurements with the use of a Mainstream system, which may also be related to the results of a previous study²²22 Cinar O, Acar YA, Arziman İ, Kilic E, Eyi YE, Ocal R. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide level of patients with acute dyspnea in ED. Am J Emerg Med. [Internet]. 2012 [Access May 18, 2016];30(2):358-61. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=2011450999&site=ehost-live
http://search.ebscohost.com/login.aspx?d... 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 study²⁰20 Pekdemir M, Cinar O, Yilmaz S, Yaka E, Yuksel M. Disparity between mainstream and sidestream end-tidal carbon dioxide values and arterial carbon dioxide levels. Respir Care. 2013 Jul;58(7):1152-6., 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 study¹⁷17 Kasuya Y, Akca O, Sessler DI, Ozaki M, Komatsu R. Accuracy of postoperative end-tidal Pco2 measurements with mainstream and sidestream capnography in non-obese patients and in obese patients with and without obstructive sleep apnea. Anesthesiology. 2009;11(3):609-15., 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 non-obese patients without OSAS since they had a better pulmonary function.

On the other hand, based on another study³⁰30 McGillicuddy DC, Tang A, Cataldo L, Gusev J, Shapiro NI, DC M, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA scores and lactic acidosis. Intern Emerg Med [Internet]. 2009 2003 [Access Oct 9, 2016];4(1):41-44. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=105639755&lang=es&site=ehost-live
http://search.ebscohost.com/login.aspx?d... 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 EtCO₂ measurement, which makes its reproducibility difficult and may lead to measurement imprecisions.

Studies focused purely on the detection of metabolic changes in adults³3 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,1818 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,3030 McGillicuddy DC, Tang A, Cataldo L, Gusev J, Shapiro NI, DC M, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA scores and lactic acidosis. Intern Emerg Med [Internet]. 2009 2003 [Access Oct 9, 2016];4(1):41-44. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=105639755&lang=es&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , aim to ratify its practical utility as a tool for clinical decision making. A study³3 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... 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 study¹⁸18 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... on patients with suspicion of sepsis, a better correlation with lactate levels was observed than in the previous study³⁰30 McGillicuddy DC, Tang A, Cataldo L, Gusev J, Shapiro NI, DC M, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA scores and lactic acidosis. Intern Emerg Med [Internet]. 2009 2003 [Access Oct 9, 2016];4(1):41-44. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=105639755&lang=es&site=ehost-live
http://search.ebscohost.com/login.aspx?d... , which may be because the sample in the last study¹⁸18 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... was twice as large (n=97 vs n=201). In addition, patients who needed OTT were included and two different measuring systems were used; a Mainstream system for patients with OTT, and a Microstream system for those with spontaneous breathing. Checking the type of capnography, it was verified the use of the Microstream system, considering that the capnograph does not have the two systems (Mainstream and Microstream). It was noticed a transcription error and, in fact, a Microstream adapter for OTT was used. These authors¹⁸18 Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. [Internet]. 2013 [Access Jul 20, 2015];31(1):64-71. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=22867820&site=ehost-live
http://search.ebscohost.com/login.aspx?d... also assessed the correlation of EtCO₂ values with mortality and lactate, indicating their use to predict mortality and the presence of septic status in these patients.

In a later study¹⁹19 Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. [Internet]. 2014 [Access Jul 20, 2015];32(2):160-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24332900
http://www.ncbi.nlm.nih.gov/pubmed/24332... ^), 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 EtCO₂, 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 work¹⁹19 Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. [Internet]. 2014 [Access Jul 20, 2015];32(2):160-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24332900
http://www.ncbi.nlm.nih.gov/pubmed/24332... , the authors indicate the need for advanced life support maneuvers and the use of Nc and OTT as inclusion criteria. It is understood that most of the data collected shall refer to patients with spontaneous ventilation, since the authors compared the predictive values of all vital signs with those values measured by capnography.

In future studies, correlations between the different groups of patients should be better analyzed according to the alkalosis or acidosis status of metabolic or respiratory origin, since strong correlations have been found between EtCO₂ and HCO₃¯ and between EtCO₂ and PaCO₂, especially in alkalotic patients. This is an important factor to be taken into account, since the physiological compensatory response of metabolic acidosis is respiratory alkalosis, which can also occur in other common pathologies such as anxiety crisis.

In addition, it should be noted that EtCO₂ values are influenced by various physiological factors, such as tissue metabolism, venous circulation, cardiac output, alveolar perfusion, and alveolar ventilation per minute²²22 Cinar O, Acar YA, Arziman İ, Kilic E, Eyi YE, Ocal R. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide level of patients with acute dyspnea in ED. Am J Emerg Med. [Internet]. 2012 [Access May 18, 2016];30(2):358-61. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=2011450999&site=ehost-live
http://search.ebscohost.com/login.aspx?d... . Any change of any of these factors will directly affect the EtCO₂ values, so there is the feasibility of getting low values, which are indicative of acidosis, whereas the problem may be changes in the perfusion or ventilation rather than metabolism.

According to the literature reviewed, it should also taken into account that in the case of a patient with extremely low EtCO₂ values and severe symptomatology, it can be assumed that he probably suffers from some severe pathology, which is causing this alteration and will require emergency medical assistance. This may also be the case of a patient with pulmonary thromboembolism, severe or respiratory heart failure, hemorrhagic shock, etc. For this reason, in several studies (especially pediatric), patients with cardiac, pulmonary or renal problems were excluded.

In general, it was observed a deficit in the control group with healthy patients in all the studies assessed, lack of information on the measuring instruments and duration of the measurements, for example, eight studies did not specify the duration of the measurements. The sample sizes were small and convenience sampling was used, as most authors indicated in their limitations. It is not possible to extrapolate the results in relation to the measuring equipment because several capnograph models were used (Table 3). All these factors, added to the variability of the measurements, types of patients and pathologies, characterize a heterogeneity that does not allow making viable comparisons between the studies. However, among all the studies, only four ventured to adjust the cut-off values³3 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. [Internet]. 2013 Nov [Access Jul 20, 2015];14(6):590-4. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=24381677&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,2323 Gilhotra Y, Porter P. Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography. J Paediatr Child Health. 2007 Oct;43(10):677-80.^-2424 Nagler J, Wright RO, Krauss B, RO W, Krauss B, Wright RO, et al. End-tidal carbon dioxide as a measure of acidosis among children with gastroenteritis. Pediatrics [Internet]. Am Acad Pediatrics. [Internet]. 2006 [Access Jul 15, 2015];118(1):260-7. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=ccm&AN=106343444&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ^,2929 Kartal M, Eray O, Rinnert S, Goksu E, Bektas F, Eken C. ETCO2: a predictive tool for excluding metabolic disturbances in nonintubated patients. Am J Emerg Med [Internet]. 2011 [Access Oct 9, 2016];29(1):65-9. Available from: http://search.ebscohost.com/login.aspx?direct=true&AuthType=ip,url,cookie,uid&db=mdc&AN=20825776&site=ehost-live
http://search.ebscohost.com/login.aspx?d... ⁾ by means of a Receiver Operating Characteristic curve (ROC), finding average values, from 24.5 mmHg, the lowest, to 36 mmHg, the highest, as the upper cutoff point to rule out the possibility of acidosis. Values from 24.5 to 31 mmHg could indicate the probability of acidotic status. As can be seen, the amplitude of the upper cutoff values was 11.5 mmHg, whereas the lower cutoff values show an amplitude less than 6.5 mmHg between the values found. Due to the high variability in the data available up to now, it is not possible to recommend precise cutoff values for the use of this parameter in clinical decision making.

Conclusion

Most of the studies found results with a good correlation between EtCO₂ and HCO₃ ^¯, or between EtCO₂ and blood PCO₂. Although further studies are needed to evaluate these associations, it is possible to suggest that the scientific evidence supports the potential use of capnography as a new sign, biomarker or complementary sentinel parameter to detect those patients with severe disease and it can be easily implemented for use in spontaneous breathing patients.

While EtCO₂ values above 24.5-36 mmHg appear to exclude metabolic acidosis status, EtCO₂ values less than 24.5-31 mmHg are indicative of acidotic status. Therefore, low capnography values, especially less than 24.5 mmHg in patients with other signs or symptoms associated with some severe pathology, may indicate the need for more specific tests and avoid delays in assistance, thus reducing morbidity and mortality in the emergency settings.

Acknowledgments

To the Research Department of SATSE Baleares for the support in the review of the bibliographic research.

References

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