Sage Journals: Discover world-class research

Abstract

Monitoring CO₂ levels in intubated neonates is highly relevant in the face of complications associated with altered CO₂ levels. Thus, this review aims to present the scientific evidence in the literature regarding the correlation between arterial carbon dioxide measured by non-invasive methods in newborns submitted to invasive mechanical ventilation. The search was carried out from January 2020 to January 2021, in the Scopus, Medline, The Cochrane Library, Web of Science, CINAHL and Embase databases. Also, a manual search of the references of included studies was performed. The main descriptors used were: “capnography,” “premature infant,” “blood gas analysis,” and “mechanical ventilation.” As a result, 221 articles were identified, and 18 were included in this review. A total of 789 newborns were evaluated, with gestational age between 22.8 and 42.2 weeks and birth weight between 332 and 4790 g. Capnometry was the most widely used non-invasive method. In general, the correlation and agreement between the methods evaluated in the studies were strong/high. The birth weight did not influence the results. The gestational age of fewer than 37 weeks implied, in its majority, a moderate correlation and agreement. Therefore, we can conclude that there was a predominance of a strong correlation between arterial blood gases and non-invasive methods, although there are variations found in the literature. Even so, the results were promising and may provide valuable data for future studies, which are necessary to consolidate non-invasive methods as a reliable and viable alternative to arterial blood gasometry.

Keywords

capnography transcutaneous blood gas monitoring artificial respiration newborn blood gas analysis

Introduction

Respiratory disorders are among the main factors responsible for the admission of newborns (NBs) to Neonatal Intensive Care Units (NICUs),¹ with an estimated frequency between 50.5% and 74.8% in Brazil.^2,3 Arterial blood gas, widely used in NICUs, is considered the gold standard for blood gas analysis since it allows the assessment of possible respiratory, metabolic and circulatory disorders.⁴ However, it is an invasive exam, requiring arterial puncture, often difficult to perform,⁵ and can cause pain, infection, and harmful blood loss for hemodynamically unstable newborns.^6,7 Besides, its result may be influenced by technical issues such as the time between sample collection and sending it to the laboratory.

Non-invasive assessment methods such as capnometry and transcutaneous carbon dioxide measurement are alternatives to arterial gasometry for monitoring newborns submitted to some ventilatory support, preventing frequent blood collections. Transcutaneous measurement of CO₂ (tcCO₂) is based on the diffusion of CO₂ through body tissues, which can be detected by a sensor positioned on the skin surface.⁸ Capnometry quantifies the level of CO₂ throughout the respiratory cycle by means of its concentration in exhaled air at the end of exhalation (PetCO₂). It is used for successful verification of orotracheal intubation, assessment of pulmonary circulation and respiratory status, and optimization of mechanical ventilation.⁹ The equipment used are capnometers, lateral flow (sidestream) or main flow (mainstream). In the mainstream, the sensor is connected directly to the endotracheal tube as part of the intubated patients’ respiratory circuit. On the other hand, in the sidestream, the sensor is located in the equipment's central unit, where the gases are analyzed.^10,11

CO₂ is transported by hemoglobin to the lungs to be exhaled. The lungs have areas perfused by the bloodstream where gas exchange occurs, called alveolar ventilation, and areas that serve only for air conduction, called anatomical dead space. On the other hand, the physiological dead space refers to areas destined for gas exchange without effective function.¹¹ The balance between ventilation (V) and perfusion (Q) in the lung regions is essential for gas exchange. Some diseases can alter the V/Q ratio causing hypoxemia or hypercapnia. Thus, the comparison of the amount of CO₂ exhaled with the amount of CO₂ in arterial blood represents a good estimate of the V/Q ratio.¹¹ Numerous studies have shown a good correlation between PaCO₂ and PetCO₂, both in adults^12-15 and children.^16,17 However, in newborns and preterm infants, there are still few studies and reliable results. In this context, this review aims to present the scientific evidence in the literature regarding the correlation of arterial CO₂ with CO₂ measured with non-invasive methods in newborns undergoing invasive mechanical ventilation (IMV).

Material and Methods

This review was carried out according to the protocol recommended by the Joanna Briggs Institute.¹⁸ The included studies were listed based on the mnemonic strategy PCC—Population, Concept and Context, in which: P corresponds to newborns submitted to invasive mechanical ventilation; C is the correlation of arterial CO₂ with CO₂ from non-invasive methods; C means NICU. Therefore, based on this strategy, the guiding question was defined: “What is the existing scientific evidence on arterial carbon dioxide measured by non-invasive methods in newborns submitted to IMV?

The search was carried out between January 2020 and January 2021, without delimitation of publication period in the following databases: Scopus, Medline, The Cochrane Library, Web of Science and CINAHL based on descriptors defined by consultation with Medical Subject Headings (MeSH) and synonyms in the English language. The following search strategy was used: (Capnography OR Capnometry OR “Transcutaneous carbon” OR “Carbon dioxide” OR “arterial carbon dioxide monitoring” OR “expired carbon dioxide”) AND (“Premature babies” OR “premature babies” OR newborn OR “very low birth weight”) AND (“Blood gas analysis”) AND (“mechanical ventilation” OR “neonatal ventilation”). In the Embase database, the search for Embase Subject Headings (Emtree) and synonyms in English was performed: (Capnometry OR “Transcutaneous carbon” OR “Carbon dioxide” OR “arterial carbon dioxide monitoring” OR “expired carbon dioxide”) AND (Prematurity OR “premature babies” OR newborns OR “very low birth weight babies”) AND (“Blood gas analysis”) AND (“artificial ventilation” OR “ventilation for newborns”). The research was limited to studies published in Portuguese, English, Spanish, and French. Complementary, a search was made from other sources, such as studies in progress in the Brazilian Clinical Trials Records (REBEC) and the US National Library of Medicine (NIH Clinical Trials). A manual search was performed in references of included studies.

From the initial search strategy, the selected articles were obtained by title and abstract by 2 authors independently (IPMM and AMN) to exclude duplicate articles and those that did not reach this review’s goals. The inclusion criteria were observational studies and clinical trials that reported using blood gas analyses and non-invasive methods to predict CO₂ in newborns, with post-birth age up to six months, admitted to NICU to assess IMV. Studies carried out in children longer than six months or in adults, and in surgical environments, the emergency room and emergency care were excluded. Eventual disagreements between reviewers were resolved by consensus, and the agreement between them was measured by applying a Cohen¹⁹ Kappa statistic. The reference manager Mendeley was used to assist in the articles’ screening.

In its turn, the screened articles in the previous step had their eligibility confirmed by reading in full, also carried out by a pair of reviewers independently (IPMM and AMN). Disagreement cases were assessed by a third reviewer (PKH). From the included articles, characteristics were extracted by a pair of reviewers independently for narrative analysis. Then, the following data were extracted: authors, year of publication, sample, measurements, birth weight (in grams), gestational age (in weeks), main comorbidities, non-invasive method, reference standard, results, and conclusion. The presentation and discussion of the results were carried out descriptively.

Ethical Approval and Informed Consent

As this is a review, this study does not involve data collection in any form (tests, experiments, observation, interviews, questionnaires, evaluation of medical records) with human beings. Therefore, submission and approval by the institution's ethics committee does not apply.

Results

We identified 127 articles in the Scopus (98), Pubmed/Medline (10), Cochrane (10), Web of Science (1), CINAHL (4), and Embase (4) databases. In REBEC, 94 were identified, and none in the NIH clinical trials, totalling 221. After excluding 6 duplicate articles, we evaluated 215 by title and abstract, and after this 190 were excluded. The following reasons led to the exclusion: the titles and abstracts did not involve a comparative analysis among the methods of measuring CO₂ levels in an invasive and non-invasive; many studies were carried out in older children, adolescents, adults, and animals; and, finally, some of the publications did not correspond to articles but theses, monographs and books. After reading 25 articles in full and applying the eligibility criteria, 19 articles were excluded because the analysis of arterial blood gas was not performed, the newborns were submitted to non-invasive MV, environments outside the NICU and analysis of graphical waves of exhaled CO₂. Therefore, 6 articles were included. From the manual search in the references, 12 other articles were added at the end of the process, totaling 18 articles in the final sample. The kappa index showed an agreement of 0.889 between the reviewers, classified as almost perfect.²⁰ The search and selection process are presented in the flowchart (Figure 1), according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA).²¹

Figure 1.

Flowchart of the stages of identification, screening and selection of articles.

Population

A total of 789 NBs were evaluated in the 18 articles, and in only 760 NBs, arterial blood gases were used. The gestational age (GA) of newborns ranged from 22.8 to 42.2 weeks. In 8 studies, all newborns assessed were premature with GA less than 37 weeks.^22-29 Birth weight ranged from 332 to 4790 g, and in some studies, only newborns with extremely low birth weight,²⁵ very low birth weight²² and low birth weight were included.²⁴

The respiratory distress syndrome (RDS), meconium aspiration syndrome (SAM) and pneumonia were the main comorbidities associated with the newborns who had participated of the studies. The authors excluded neonates with congenital heart disease from most studies. The characteristics of the included studies population were classified according to the main author, year of publication, and type of study are shown in Table 1.

Table 1.

Characteristics of the Population Sample of the Articles Included.

Author	Sample (NB)	Measurements (method-PaCO₂)	Gestational age (week)	Comorbidities
Meredith and Monaco³⁰	16	132 PetCO₂	22-40	RDS, sepsis, MAS, asphyxia
Nangia et al³¹	152	152 ETCO₂	28-42	Asphyxia, MAS, RDS
Rozycki et al²⁶	48	411 EtCO₂	28.3 ± 4.7	Pulmonary disease
Wu et al³²	61 (20 e 41 Premature Infants)	130 PetCO₂	31.4 (22.8-42.2)	RDS, heart diseases
Aliwalas et al²⁷	27 (Premature Infants)	81 PetCO₂ e TcPCO₂	Mean 26.3 (<28)	RDS
Singh and Singhal²⁵	31 (ELBW <1000 g)	754 EtCO₂	23-27	RDS
Kugelman et al³³	27	222 DETCO₂ e 212 PETCO₂	32.5 (24.8-40.8)	RDS, TEF
Bernet et al³⁴	20	82 PtcCO₂	38.25 (29-41)	DH, NEC, RDS
Bhat andAbhishek⁶	32	133 EtCO₂	27-40	RDS, MAS, sepsis, asphyxia
Kugelman et al²⁸	16 (Premature Infants)	195 dCap	27.1 (24.7-34.7)	RDS
Trevisanuto et al²²	45 (VLBW)	143 ETCO₂	23-33	RDS
Singh et al³⁵*	48 AA: 29 (22 VLBW e 7 no-VLBW)	286 EtCO₂ AA: 160 (119 VLBW 41 no-VLBW )	VLBW: 26.3 ± 2.3 No-VLBW: 36.2 ± 2.9	VLBW: RDS, IVH, ROP No-VLBW: GTC, RD
Tingay et al³⁶	50	132 EtCO₂/TcCO₂	Mean 37	IO, TEF
Mukhopadhyay et al²³**	123 (52 após PtcCO₂) AS:42	1338 PtcCO₂ AS: 774	27.7 ± 3.9	RDS, MAS, PNPH, RD
Kugelman et al³⁷	24	332 dCap	26.8 (23.6-38.6)	RDS, PH
Kugelman et al³⁸	55 (25- OG; 30 - CG)	761 dETCO₂	OG: 29.1 (24.5-39) CG: 28.2 (23.5-37.9)	OG: RDS, TTN, PH CG: RDS, TTN, PH
Lin et al²⁴	34 (Premature Infants)	101 PetCO₂ (53 VLBW e 48 no-VLBW)	VLBW: 28.3 ± 1.8 No-VLBW: 32.3 ± 1.9	BPD, PDA, RDS
Nakato et al²⁹	51 (Premature Infants)	221 EtCO₂	28.08 + 3.19	RDS, sepsis

Abbreviations: Newborn, newborn; ELBW, extremely low birth weight; VLBW, very low birth weight; AA, arterial samples; OG, open group; CG, closed group; ETCO₂, end-tidal carbon dioxide; DETCO₂, distal end-tidal carbon dioxide; PETCO₂, proximal end-tidal carbon dioxide; PetCO₂, end-tidal carbon dioxide pressure; PtcCO₂ = TcPCO2, transcutaneous carbon dioxide; dCap, distal capnography; RDS, respiratory distress syndrome; TEF, tracheoesophageal fistula; MAS, meconium aspiration syndrome; NEC, necrotizing enterocolitis; DH, diaphragmatic hernia; IVH, intraventricular hemorrhage; ROP, retinopathy of prematurity; RD, respiratory distress; IO, intestinal obstruction; GTC, gastroschisis; PH, pulmonary hypertension; TTN, transient tachypnea of the newborn; BPD, bronchopulmonary dysplasia; PDA, persistence of the ductus arteriosus; PNPH, persistent neonatal pulmonary hypertension.

The values of gestational age, birth weight and comorbidities are for all patients, not discriminating against those who only received arterial blood collection.

The values of gestational age and birth weight refer to all patients who were evaluated with PtcCO₂, without discrimination regarding arterial blood collections.

Non-Invasive Methods

Two articles used tcCO₂,^23,34 and only 2 studies used both tcCO₂ and PetCO₂.^27,36 The other articles evaluated the estimate of arterial CO₂ by capnometry, in which half of these used lateral flow capnometers and the others mainstream. The measurement performed in the non-invasive method occurred continuously (without pauses) in the majority of the studies.^{22,23,27,29,32,35} The measurement was recorded simultaneously with blood collection in most of the articles. In 2 studies it occurred before collection,^28,34 1 after the collection³⁰ and another before and after collection.³⁶ The umbilical artery was the primary arterial access used. The description of non-invasive methods evaluated in the studies is shown in Table 2.

Table 2.

Characteristics of the Non-Invasive Methods Evaluated in the Studies and the Gold Standard.

Author	Non-invasive method: exhaled or transcutaneous CO₂ (measurement)	Reference standard-arterial gasometry (sample)
Meredith and Monaco³⁰	Mainstream-continuous, record after blood collection	Umbilical or peripheral artery
Nangia et al³¹	Sidestream-continuous, record simultaneous with blood collection	Radial artery
Rozycki et al²⁶	Mainstream-continuous, record simultaneous with blood collection	Arterial catheter
Wu et al³²	Mainstream-no continuous, record simultaneous with blood collection	Umbilical or radial artery
Aliwalas et al²⁷	Sidestream microstream and transcutaneous: no continuous, record simultaneous with blood collection	Umbilical artery
Singh and Singhal²⁵	Mainstream-continuous	Umbilical or radial artery
Kugelman et al³³	Sidestream (DETCO₂), mainstream (PETCO₂)-continuous, record simultaneous with blood collection	Arterial catheter
Bernet et al³⁴	Transcutaneous continuous-TOSCA: before blood collection; MicroGas: simultaneous with blood collection	Umbilical, radial or posterior tibial artery
Bhat andAbhishek⁶	Mainstream-continuous, record simultaneous with blood collection	Arterial catheter
Kugelman et al²⁸	Sidestream microstream-continuous, record simultaneous with blood collection	Arterial catheter
Trevisanuto et al²²	Mainstream-no continuous, record simultaneous with blood collection	Umbilical artery
Singh et al³⁵	Sidestream microstream-no continuous, record simultaneous with blood collection	Arterial (when available), capillary or venous
Tingay et al³⁶	Sidestream microstrem e transcutânea–continuous, record before and after blood collection	Arterial catheter
Mukhopadhyay et al²³	transcutaneous no continuous, record simultaneous with blood collection	Arterial catheter
Kugelman et al³⁷	Sidestream microstream-continuous, record simultaneous with blood collection	Arterial catheter
Kugelman et al³⁸	Sidestream microstream-continuous, record simultaneous with blood collection	Arterial catheter
Lin et al²⁴	Mainstream-continuous, record simultaneous with blood collection	Umbilical artery, collected 1h before the surfactant

Abbreviations: DETCO₂, distal end-tidal carbon dioxide; PETCO₂, proximal end-tidal carbon dioxide; PetCO₂, end-tidal carbon dioxide pressure; dCap, distal capnography.

Correlation and Agreement Between Non-Invasive and Arterial CO₂

Statistical tests verified the correlation and agreement analysis of the methods. The correlation coefficients and Bland-Altman analysis of agreement were most used. In general, the correlation of the methods was considered strong in 12 articles, moderate in 4 and weak in 1 article.

The Bland-Altman concordance analysis was applied in all studies that evaluated this parameter, having been considered high in 8 articles, moderate in 1 and low in 8.

For the articles that analyzed the influence of birth weight on the correlation and agreement between the methods, in 5 of them there was no influence, maintaining a strong correlation, ^{22,26,28,33,38} high agreement,^28,33,38 and low agreement.^22,26 In 3 others, there was a decrease in correlation and agreement,³⁵ only in agreement³⁷ and only in correlation when weight was less than 1500 g.³¹

In studies that analyzed exclusively preterm infants, the correlation was strong^{22,25,26,28,29} and moderate.^24,27 The agreement was high,^25,28,30 moderate^23,29 and low.^22,24,35 One study compared the correlation and agreement between term and premature NBs, that both were high.³² Another study found only the correlation, which was strong in term and preterm NBs from 28 to 32 weeks and moderate in preterm infants from 32 to 37.³¹

About lung diseases, in 2 studies the correlation was greater in newborns with RDS using surfactant than in those who did not use it.^6,24 In 2 studies, newborns with moderate and severe lung disease maintained a strong high correlation,^29,37and in only one, the correlation was moderate in the presence of SDR.³¹ Details about the statistical tests, the correlation and agreement values are shown in Table 3, and the conclusion of the results are shown in Table 4.

Table 3.

Main Results of the Included Articles.

Author	Results
Meredith and Monaco³⁰	PetCO₂ /PaCO₂: r = 0.79, P < .001; AG: 0.86 ± 0.14 torr
Nangia et al³¹	EtCO₂/ PaCO₂: IG 28-32 s: r = 0.73, P < .01/IG 32-37 s: r = 0.61, P < .001/IG 37-41 s: r = 0.81, P < .001/<1.5 kg: r = 0.62, P < .01/−1.5-2.5 kg: r = 0.92, P < .001; >2.5 kg: r = 0.81, P < .001/MAS: r = 0.94, P < .001/Severe asphyxia: r = 0.76, P < .001/Recurrent apnea: r = 0.96, P < .001/RDS: r = 0.55, P < .01-0.001
Rozycki et al²⁶	EtCO₂/PaCO₂: r = 0.833, P < .001; AG: −6.9 ± 6.9 mmHg (CI 95%: ±11.5 mmHg)
Wu et al³²	PetCO₂ /PaCO₂: r = 0.818, P < .001; AG: 3.5 ± 7.1 mmHg (CI95%: 2.2 a 4.7)
Aliwalas et al²⁷	PetCO₂ /PaCO₂: 4 hours: ICC = 0.61; AG: −0.3 ± 2.2 mmHg/12 hours: ICC = 0.56; AG: 2.4 ± 1.4 mmHg/24 hours: ICC = 0.57; AG: 1.9 ± 1.8 mmHg\|TcPCO₂/PaCO₂: 4 hours: ICC = 0.45; AG: 2.2 ± 2.3 mmHg /12 hours: ICC = 0.73; AG: 4.4 ± 1.2 mmHg; 24 hours: ICC = 0.53; AG: 2.6 ± 1.8 mmHg
Singh and Singhal²⁵	EtCO₂/PaCO_2: r = 0.71; ICC = 0.81, P < .0001; AG: 5.6 ± 6.8 mmHg (CI 95% 5,11 a 6.09)
Kugelman et al³³	Distal EtCO₂/PaCO₂: r = 0.72, P < .001; AG: −1.5 ± 8.7 mmHg\|Proximal EtCO₂/PaCO_2: r = 0.21, P < .005; AG: −10.2 ± 13.7 mmHg
Bernet et al³⁴	PtcCO₂Tosca/PaCO₂: AG: 0.14 ± 1.45 kPa (CI 95%: −1.31 a 1.59)\|PtcCO₂/PaCO₂MicroGas (Conventional): AG: -0.08 ± 1.2 kPa (CI 95%: −1.28 a 1.12)
Bhat andAbhishek⁶	EtCO₂/PaCO₂: r = 0.73, P < .001; AG: -6.65 ± 7.54 mmHg (CI 95%: −7.9 a −5.35)
Kugelman et al²⁸	dCap/PaCO₂: r = 0.68, P < .0001; AG: -2 ± 10.7 mmHg
Trevisanuto et al²²	EtCO₂/PaCO₂: r = 0.69, P < .0001; AG: 13.5 ± 8.4 mmHg (CI 95%: −3 a 29.9)
Singh et al³⁵	EtCO₂/PaCO_2: r = 0.68; AG: 7.29 ± 10.2 mmHg (CI 95%: 27.12 a −12.55)
Tingay et al³⁶	EtcCO2/PaCO2: AG: 4.1 ± 9.0 mmHg \| TcCo₂/PaCO₂: AG: -0.8 ± 13.0 mmHg
Mukhopadhyay et al²³	PtcCO₂/PaCO₂: AG: −7.2 ± 16 mmHg
Kugelman et al³⁷	dCap/PaCO₂: r = 0.7, P < .001; AG: −11.7 ± 10.3 mmHg
Kugelman et al³⁸	dEtCO₂ /PaCO₂: r = 0.73, P < .001; AG: 3 ± 8.5 mmHg
Lin et al²⁴	PetCO₂ /PaCO₂: r = 0.603, P < .01; AG: 5.9 ± 7.6 mmHg
Nakato et al²⁹	EtCO₂/PaCO₂: r = 0.853, P < .001; AG: 0.352 ± 7.57 mmHg (CI 95%: 14.5-15.2)

Abbreviations: r, correlation coefficient; AG, agreement; ICC, intraclass correlation coefficient; EtCO₂, end-tidal carbon dioxide; dETCO₂, distal end-tidal carbon dioxide; PtcCO₂ = TcPCO₂, transcutaneous carbon dioxide; dCap, distal capnography; GA, gestational age; RDS, respiratory distress syndrome; SAM, meconium aspiration syndrome.

Table 4.

Conclusion of the Included Articles.

Author	Conclusion
Meredith and Monaco³⁰	Strong correlation and high agreement
Nangia et al³¹	Strong correlation: birth weight between 1.5 e 2.5 kg, MAS, recurrent apnea, premature infants of 28-32 s, Term NBs, >2.5 kg and severe asphyxia; Moderate correlation : premature infants (32-37 s), birth weight <1.5 kg e RDS
Rozycki et al²⁶	Strong correlation and low agreement
Wu et al³²	Strong correlation and low agreement
Aliwalas et al²⁷	Moderate correlation
Singh and Singhal²⁵	Strong correlation and high agreement
Kugelman et al³³	Strong correlation and high agreement for the distal method; Weak correlation and low agreement for the proximal method
Bernet et al³⁴	Low agreement
Bhat andAbhishek⁶	Strong correlation and high agreement
Kugelman et al²⁸	Strong correlation and high agreement
Trevisanuto et al²²	Strong correlation and low agreement
Singh et al³⁵	Moderate correlation and low agreement
Tingay et al³⁶	High concordance
Mukhopadhyay et al²³	Moderate agreement
Kugelman et al³⁷	Strong correlation and low agreement
Kugelman et al³⁸	Strong correlation and high agreement
Lin et al²⁴	Moderate correlation and low agreement
Nakato et al²⁹	Strong correlation and high agreement

Abbreviations: RDS, respiratory distress syndrome; MAS, meconium aspiration syndrome.

Discussion

The correlation and agreement between invasive and non-invasive methods for CO₂ analysis in newborns, especially in premature infants, is divergent in the literature. The newborns studied in this review had comorbidities, which can compromise the agreement of the methods. Despite the differences between the selected articles, such as GA, birth weight and comorbidities, many articles showed a strong correlation and agreement between the methods.

The non-invasive methods showed in this review were PetCO₂/EtCO₂ and tcCO₂. TcCO₂ were performed in few studies. It is a method that can be used in invasive and non-invasive ventilation and even in unventilated patients, while the expired CO₂ is used in IMV.⁸ One criteria of the review were to include the newborns submitted to IMV, which can have affected the smaller number of studies with a transcutaneous approach.

Among the studies that used tcCO₂, a moderate correlation and agreement was found and a low agreement. Although in other studies, they are strong in critically ill newborns³⁹ and very low birth weight newborns (VLBW).⁴⁰

The RDS, or hyaline membrane disease, was the comorbidity most associated with neonates in the studies included in this review. It is the leading cause of pulmonary involvement in newborns, especially in premature infants, with ventilatory management as one of the pillars of treatment, including the IMV.⁴¹ In general, the correlation between EtCO₂ and PaCO₂ with lung disease was considered strong, although it has also been found weak in literature.⁴² In severe lung disease cases, the correlation and agreement were less reliable,³⁵ as demonstrated by another study.⁴³ The correlation was higher after the use of surfactant for RDS;²⁴ however, in another study, the correlation and agreement showed moderate after surfactant use.²⁷ A literature review that analyzed the prediction of PaCO₂ through EtCO₂ indicates that the correlation between the methods is stronger if no present lung disease.⁴⁴

In only one study,³² cardiopulmonary malformation appeared among the newborns' comorbidities, although it was a reason for exclusion in most articles. In situations of cyanotic congenital anomalies, PetCO₂ can be accurate and, however, underestimate PaCO₂. In acyanotic anomalies, the correlation of PetCO₂ with PaCO₂ shows agreement.⁴⁵

There was variation for correlation and agreement between PetCO₂ and PaCO₂ associated to birth weight. In extremely low birth weight (ELBW) and very low birth weight (VLBW), the most correlations and concordances were strong/high. In Low birth, weight (LBW) showed moderate correlation and low agreement.²⁴ On the other hand, there is evidence that birth weight does not interfere with the agreement between PetCO₂ and PaCO₂.⁴⁶

About the gestational age, most studies ranged from preterm to post-term, and others exclusively preterm infants. The correlation in these cases was divided between strong and moderate, and the agreement was predominantly moderate. In the literature, a study⁴⁷ carried out with preterm infants found a linear correlation between TcPCO₂ and PaCO₂ and another⁴⁶ showed that gestational age does not influence the agreement between PetCO₂ and PaCO₂.

This review did not include review studies and grey literature and delimitation of primary studies and language restriction. However, two reviewers extracted the articles independently, with subsequent consensus, showing excellent agreement.

This review showed some limitations, as most studies were cross-sectional, uncontrolled, and with small samples,^{25,27,28,33-35,37} selected for convenience and making it impossible to determine selection's fundamental criteria. There was variation in the measurements that occurred before and after the blood collection or simultaneously. Variations in the sample population were also identified in terms of age, birth weight, gestational age, and newborns’ comorbidities. Therefore, the heterogeneity of the included studies does not allow a comparison between their results.

In general, the correlation and agreement between CO₂ from non-invasive methods with arterial blood gases showed to be strong/high in this review, although moderate and weak/low values were found. Non-invasive methods can help indicate considerable changes in PaCO₂ levels to avoid excessive blood sampling and reduce the exposure time to hypocapnia and hypercapnia. Furthermore, they can optimize professionals’ clinical evaluation while blood collection from arterial blood gases is a complicated process compared to the non-invasive measure.

More studies and greater methodological rigor need to confirm that the CO₂ measurement by non-invasive methods and so permit the construction of specific protocols to guide the professionals who work in NICUs. The studies’ results have shown promise that they can provide valuable data for future investigations, which are necessary to consolidate non-invasive methods as a viable and reliable alternative to arterial blood gases.

Footnotes

Acknowledgements

We thank Fundação Araucária, Secretaria de Estado da Ciência, Tecnologia e Ensino Superior do Paraná (SETI), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for scholarships.

Author Contributions

All authors conceptualized and designed the study. IPMM contributed on the acquisition, analysis, and interpretation of data, and drafted the manuscript. AMN and PKH contributed on conceptualization, methodology and drafted the manuscritpt. PKH, AMN, SOI, and PN contributed on data analysis and interpretation, reviewed, and approved the final draft of the manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Ingra Pereira Monti Martins

Paula Karina Hembecker

Percy Nohama

References

Basso

Neves

Silveira

Associação entre realização de pré-natal e morbidade neonatal. Texto Contexto Enferm. 2012;21:269-276. doi:10.1590/S0104-07072012000200003

Tadielo

Neves

Arrué

, et al. Morbidade e mortalidade de recém-nascidos em tratamento intensivo neonatal no sul do Brasil. Rev Soc Bras Enferm Ped. 2013;13:7-12. doi:10.31508/1676-3793201300002

Lima

Silva

Avila

PES

Nicolau

Neves

PFM

. Aspectos clínicos de recém-nascidos admitidos em Unidade de Terapia Intensiva de hospital de referência da Região Norte do Brasil. ABCS Health Sci. 2015;40:62-68. doi:10.7322/abcshs.v40i2.732

Gattinoni

Pesenti

Matthay

Understanding blood gas analysis. Intensive Care Med. 2018;44:91-93. doi:10.1007/s00134-017-4824-y

Zeserson

Goodgame

Hess

, et al. Correlation of venous blood gas and pulse oximetry with arterial blood gas in the undifferentiated critically ill patient. J Intensive Care Med. 2016;33:176-181. doi:10.1177/0885066616652597

Bhat

Abhishek

Mainstream end-tidal carbon dioxide monitoring in ventilated neonates Mainstream end-tidal carbon dioxide monitoring in ventilated neonates. Singapore Med J. 2008;49:199-203.

Mota

Queiroz

RS.

Distúrbios do equilíbrio ácido básico e gasometria arterial: uma revisão crítica. Rev Digital Buenos Aires. 2010;14:1.

Hochwald

Borenstein-Levin

Dinur

Jubran

Ben-David

Kugelman

Continuous noninvasive carbon dioxide monitoring in neonates: from theory to standard of care. Pediatrics. 2019;144:e20183640. doi:10.1542/peds.2018-3640

Walsh

Crotwell

Restrepo

RD.

Capnography/capnometry during mechanical ventilation: 2011. Respir Care. 2011;56:503-509. doi:10.4187/respcare.01175

10.

Kerslake

Kelly

Uses of capnography in the critical care unit. BJA Educ. 2017;17:178-183. doi:10.1093/biaed/mkw062

11.

Riley

CM.

Continuous capnography in pediatric intensive care. Crit Care Nurs Clin NA. 2017;29:251-258. doi:10.1016/j.cnc.2017.01.010

12.

Pishbin

Ahmadi

Sharifi

Deloei

Shamloo

Reihani

The correlation between end-tidal carbon dioxide and arterial blood gas parameters in patients evaluated for metabolic acid-base disorders. Electron Physician. 2015;7:1095-1101. doi:10.14661/2015.1095-1101

13.

Yosef

Hay

Nasri

Magen

Reisin

End tidal carbon dioxide as a predictor of the arterial PCO₂ in the emergency department setting. Emerg Med J. 2004;21:557-559. doi:10.1136/emj.2003.005819

14.

Cereceda-Sánchez

Molina-Mula

Capnografia como ferramenta para detectar alterações metabólicas em pacientes atendidos em situações de emergência. Rev Lat Am Enfermagem. 2017;25:1-10. doi:10.1590/1518-8345.1756.2885

15.

Cinar

Acar

Arziman

Kilic

Eyi

Ocal

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. 2012;30:358-361. doi:10.1016/j.ajem.2010.12.014

16.

Mcswain

Hamel

Smith

, et al. End-tidal and arterial carbon dioxide measurements correlate across all levels of physiologic dead space. Respir Care. 2010;55:288-293.

17.

Mehta

Kashyap

Trivedi

Correlation of end tidal and arterial carbon dioxide levels in critically ill neonates and children. Indian J Crit Care Med. 2014;18:348-353. doi:10.4103/0972-5229.133874

18.

Peters

MDJ

Godfrey

McInerney

Munn

Tricco

Khalil

. JBI reviewer’s manual for evidence synthesis. Chapter 11: scoping reviews (2020 version). Joanna Briggs Institute. Updated 2020. Accessed April 5, 2021. https://synthesismanual.jbi.global

19.

Cohen

Weighted Kappa: nominal scale agreement with provision for scaled disagreement or partial credit. Psychol Bull. 1968;70:213-220. doi:10.1037/h0026256

20.

Landis

Koch

GG.

The measurement of observer agreement for categorical data. Biometrics. 1977;33:159-174. doi:10.2307/2529310

21.

Moher

Liberati

Tetzlaff

Altman

, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. doi:10.1371/journal.pmed.1000097

22.

Trevisanuto

Giuliotto

Cavallin

Doglioni

Toniazzo

Zanardo

End-tidal carbon dioxide monitoring in very low birth weight infants: correlation and agreement with arterial carbon dioxide. Pediatr Pulmonol. 2012;372:367-372. doi:10.1002/ppul.21558

23.

Mukhopadhyay

Maurer

Puopolo

KM.

Neonatal transcutaneous carbon dioxide monitoring–effect on clinical management and outcomes. Respir Care. 2016;61:90-97. doi:10.4187/respcare.04212

24.

Lin

Huang

Hsiao

Chiang

Jeng

MJ.

End-tidal carbon dioxide measurement in preterm infants with low birth weight. PLoS One. 2017;12:e0186408. doi:10.1371/journal.pone.0186408

25.

Singh

Singhal

Does end-tidal carbon dioxide measurement correlate with arterial carbon dioxide in extremely low birth weight infants in the first week of life?

Indian Pediatr. 2006;43:20-25.

26.

Rozycki

Sysyn

Marshall

Malloy

Wiswell

TE.

Mainstream end-tidal carbon dioxide monitoring in the neonatal intensive care unit. Pediatrics. 1998;101:648-653. doi:10.1542/peds.101.4.648

27.

Aliwalas

LLD

Noble

Nesbitt

Fallah

Shah

. Agreement of carbon dioxide levels measured by arterial, transcutaneous and end tidal methods in preterm infants ≤ 28 weeks gestation. J Perinatol 2005;25:26-29. doi:10.1038/sj.jp.7211202

28.

Kugelman

Riskin

Shoris

Ronen

Stein

Bader

Continuous integrated distal capnography in infants ventilated with high frequency ventilation. Pediatr Pulmonol. 2012;47:876-883. doi:10.1002/ppul.22524

29.

Nakato

Silva

RPGVC

Filho

NAR

. Correlation of partial pressure of arterial carbon dioxide and end-tidal carbon dioxide in intubated premature infants. Ann Pediatr Child Health. 2018;6:1140.

30.

Meredith

Monaco

FJ.

Evaluation of a mainstream capnometer and end-tidal carbon dioxide monitoring in mechanically ventilated infants. Pediatr Pulmonol. 1990;9:254-259. doi:10.1002/ppul.1950090412

31.

Nangia

Saili

Dutta

AK.

End tidal carbon dioxide monitoring-its reliability in neonates. Indian J Pediatr. 1997;64:389-394. doi:10.1007/BF02845211

32.

Chou

Hsieh

Chen

Huang

Tsao

PN.

Good estimation of arterial carbon dioxide by end-tidal carbon dioxide monitoring in the neonatal intensive care unit. Pediatr Pulmonol. 2003;35:292-295. doi:10.1002/ppul.10260

33.

Kugelman

Zeiger-Aginsky

Bader

Shoris

Riskin

A novel method of distal end-tidal CO2 capnography in intubated infants: comparison with arterial CO2 and with proximal mainstream end-tidal CO2. Pediatrics. 2008;122:e1219-e1224. doi:10.1542/peds.2008-1300

34.

Bernet

Doll

Cannizzaro

Ersch

Frey

Weiss

Longtime performance and reliability of two different PtcCO2 and SpO2 sensors in neonates. Pediatr Anesth. 2008;18:872-877. doi:10.1111/j.1460-9592.2008.02661.x

35.

Singh

Gilbert

Singh

Govindaswami

Sidestream microstream end tidal carbon dioxide measurements and blood gas correlations in neonatal intensive care unit. Pediatr Pulmonol. 2013;48:250-256. doi:10.1002/ppul.22593

36.

Tingay

Mun

Perkins

EJ.

End tidal carbon dioxide is as reliable as transcutaneous monitoring in ventilated postsurgical neonates. Arch Dis Child Fetal Neonatal. 2013;98:F161-F164. doi:10.1136/fetalneonatal-2011-301606

37.

Kugelman

Bromiker

Riskin

, et al. Diagnostic accuracy of capnography during high-frequency ventilation in neonatal intensive care units. Pediatr Pulmol. 2016;51:510-516. doi:10.1002/ppul.23319

38.

Kugelman

Golan

Riskin

, et al. Impact of continuous capnography in ventilated neonates: a randomized, multicenter study. J Pediatr. 2016;168:56-61.e2. doi:10.1016/j.jpeds.2015.09.051

39.

McEvedy

McLeod

Mulera

Kirpalani

Lerman

End-tidal, transcutaneous, and arterial pco2 measurements in critically ill neonates: a comparative study. Anesthesiology. 1988;69:112-116. doi:10.1097/00000542-198807000-00020

40.

Aly

El-Dib

Mohamed

Aly

Transcutaneous carbon dioxide monitoring with reduced-temperature probes in very low birth weight infants. Am J Perinatol. 2017;34:480-485. doi:10.1055/s-0036-1593352

41.

Miyoshi

MH.

Consenso Brasileiro em Ventilação Mecânica–Suporte ventilatório na síndrome do desconforto respiratório do recém-nascido. Sociedade Brasileira de Pediatria. Updated May 25, 2017. Accessed April 5, 2021. https://www.sbp.com.br/fileadmin/user_upload/2015/02/SDR.pdf

42.

Watkins

Weindling

AM.

Monitoring of end tidal CO2 in neonatal intensive care. Arch Dis Child. 1987;62:837-839. doi:10.1136/adc.62.8.837

43.

Hagerty

Kleinman

Zurakowski

Lyons

Krauss

Accuracy of a new low-flow sidestream capnography technology in newborns: a pilot study. J Perinatol. 2002;22:219-225. doi:10.1038/sj.jp.7210672

44.

Naidu

Is ETCO2 a predictor of PaCO2 in ventilated neonates on the Neonatal Intensive Care Unit?

Work Pap Health Sci. 2012;1:1.

45.

Burrows

FA.

Physiologic dead space, venous admixture, and the arterial to end-tidal carbon dioxide difference in children undergoing cardiac surgery. Anesthesiology. 1989;70:219-225. doi:10.1097/00000542-198902000-00007

46.

Lopez

Grabar

Barbier

Krauss

Jarreau

Moriette

Detection of carbon dioxide thresholds using low-flow sidestream capnography in ventilated preterm infants. Intensive Care Med. 2009;35:1942-1949. doi:10.1007/s00134-009-1647-5

47.

Hand

Shepard

Krauss

Auld

PA.

Discrepancies between transcutaneous and end tidal carbon dioxide monitoring in critically ill neonate with respiratory distress syndrome. Crit Care Med. 1989;17:556-559. doi:10.1097/00003246-198906000-00015

Correlation of End-Tidal Carbon Dioxide with Arterial Carbon Dioxide in Mechanically Ventilated Neonates: A Scoping Review

Abstract

Keywords

Introduction

Material and Methods

Ethical Approval and Informed Consent

Results

Population

Non-Invasive Methods

Correlation and Agreement Between Non-Invasive and Arterial CO2

Discussion

Footnotes

Acknowledgements

Author Contributions

Declaration of Conflicting Interests

Funding

ORCID iDs

References

Correlation and Agreement Between Non-Invasive and Arterial CO₂