Article, Pulmonology

The accuracy of mainstream end-tidal carbon dioxide levels to predict the severity of chronic obstructive pulmonary disease exacerbations presented to the ED

a b s t r a c t

Introduction: The end-tidal carbon dioxide (ETCO₂) measurement was considered as an essential tool for the assessment of several conditions in emergency medicine. However, the Diagnostic role of capnography in dyspneic patients still remains unclear. We aimed to analyze the alteration of the ETCO₂ levels in chronic obstructive pulmonary disease (COPD) exacerbations and its role in the decision- making process.

Methods: All the individuals who were presented to the emergency department (ED) after COPD exacerbations were prospectively enrolled in the study. The patients were excluded if they refused to give informed consent, intubated after initial assessment, and had uncertain COPD diagnosis. The ETCO₂ measurement using a mainstream capnometer was undertaken in the pretreatment and post-treatment period of COPD exacerbations.

Results: A total of 102 patients were enrolled in the study. Pre-ETCO₂ and post-ETCO₂ levels were positively correlated with arterial partial carbon dioxide pressure levels (r = 0.756, P b .001 and r = 0.629, P b .001, respectively). The median pre-ETCO₂ level was 32.0 (30.5-40.5) in discharged patients and 39.0 (31.0-53.5) in admitted patients. After the initial therapy in the ED was completed, the median post-ETCO₂ level was found to be 32.0 (28.0-37.5) in discharged patients and 36.0 (32.0-52.0) in admitted patients. Although a statistically significant difference was observed in the pretreatment period (P = .043), no difference was observed in post-treatment period between ETCO₂ levels (P = .107).

Conclusion: End-tidal carbon dioxide levels were higher in admitted patients when compared with discharged patients on arrival to the ED. ETCO₂ measurement has very little contributions while evaluating patients with COPD exacerbation in the ED.

Introduction

End-tidal carbon dioxide (ETCO₂) measurement has become an essential tool for emergency medicine practice and it was also considered as a useful parameter to assess several conditions in critical patients. The main uses of end-tidal carbon dioxide measure- ment are confirming the correct placement of the endotracheal tube [1], assessing the effectiveness of cardiopulmonary resuscitation [2], and the early detection of changes in ventilation status [3-6].

Two different methods were used to measure ETCO₂ levels in selected individuals: In sidestream devices, the ETCO₂ measurement was undertaken by aspirating a small amount from the exhaled breath through tubing to a sensor connected to the circuit. On the contrary, mainstream devices measure CO₂ directly from the air passage, with the sensor located on the endotracheal tube [5,7]. Mainstream devices

* Corresponding author. Tel.: +90 262 303 85 45.

E-mail address: [email protected] (N.O. Dogan).

have been primarily used for intubated patients; however, they may be also utilized to measure ETCO₂ levels in compliant patients, who may be able to blow into the sample tube transiently [8].

According to literature, ETCO₂ monitoring is also performed with increasing frequency in non-intubated patients, who were admitted to the emergency department (ED). However, the role of capno- graphy as a reliable tool to replace the arterial assessment of partial carbon dioxide pressure (pCO₂) in dyspneic patients was not clearly demonstrated, and the literature revealed conflicting results [6,8- 10]. A prospective cohort study, consisting of patients with chronic obstructive pulmonary disease (COPD) exacerbations, concludes that ETCO₂ measurement may not be a useful parameter in predicting hypercarbia in COPD patients, although, a moderate correlation was observed [6]. As a particular population, the patients presented with COPD exacerbations constitute a significant part of ED admissions and the alteration of ETCO₂ levels in exacerbations remains unclear. This study was designed to investigate the alteration of ETCO₂ levels in COPD exacerbations and its role in the decision-making process.

Methods

Study design

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A prospective cross-sectional study was conducted on patients presented to the ED with COPD exacerbations between the dates of January and June 2013. The hospital is a 400-bed training and research hospital with 100,000 ED admissions per year. The institutional review board approval for the study was obtained, and patients were asked to sign an informed consent form before they enrolled in the study.

Selection of participants

All of the individuals who presented the ED after COPD exacerbations were included in the study. Patients were excluded if they refused to give informed consent, if they were intubated after initial assessment, and if they had an uncertain COPD diagnosis.

Outcome measures

The primary outcome variables were the values of ETCO₂, which were used to predict hospital admission in COPD exacerbations, both on arrival to the ED and after the initial treatment was completed.

Results

Fig. 1. Patient flow chart.

2.4. Study protocol

Mainstream end-tidal CO₂ levels were measured with the EMMA capnometer (EMMA(TM) Emergency Capnometer, PHASEIN AB). Before the study started, the senior emergency medicine residents and emergency physicians were trained in the use of the mainstream capnometer in non-intubated patients. ETCO₂ measurement was undertaken in a similar manner to the study by Cinar et al [8], where the patients were asked to breathe through an airway adapter attached to the mainstream portable capnometer.

Immediately after the application to the ED, the subjects were asked to breathe through the capnometer for at least 20 seconds, and the highest ETCO₂ value (pre-ETCO₂) was recorded. Patients were then treated according to the recommendations of the Global Initiative for Chronic obstructive lung disease (GOLD) guidelines

[11] with oxygen, short-acting beta-2 agonists (given every 20 minutes, if tolerated), and corticosteroids. After the first assessment and bronchodilator treatment had been accomplished, the patients were asked again to breathe through capnometer and the highest ETCO₂ value was recorded (post-ETCO₂). Vital signs, co-morbid conditions, previous admissions due to COPD exacerbations, arterial blood gas analysis results, clinical symptoms and other laboratory data were recorded on the standardized charts and the patients were followed until the ED discharge. The patients were then classified into admission criteria, which were defined by GOLD guidelines [11].

2.5. Statistical analysis

All the statistical analyses were performed using SPSS 11.0 for Windows. The Kolmogorov-Smirnov tests were used to analyze the normal distribution of the variables. The continuous independent variables were analyzed using the Mann-Whitney U and Kruskal Wallis tests. The dependent variables were analyzed using the Wilcoxon test and the results were expressed as medians with

One hundred thirty-four consecutive patients were assessed for eligibility and 32 patients were excluded from the study (Fig. 1), with the analyses performed on 102 patients. The main character- istics of the study population are shown in Table 1, where 32 of the patients (32.4%) were discharged and 69 of the patients (67.6%) were admitted to hospital using the GOLD criteria. Among the hospitalized group, 30 patients (29.4%) were admitted to the intensive care unit.

When compared with the discharged patients, the admitted patients were found to be older (P b .001), more febrile and tachycardic (P b .001), and more tachypneic (P b .001), and they had more decreased Arterial oxygen saturation levels (P b .001).

The results of the arterial blood gas analysis parameters and ETCO₂ measurement regarding the admission status are shown in Table 2. Hospitalized patients were more hypoxemic (P = .011) and more hypercapnic (P b .001), whereas the median pCO₂ level of the discharged patients was 36 mmHg (31.8-49.4) and the median level in admitted patients was 46.2 mmHg (39.3-54.7). The median pre- ETCO₂ level was 32.0 (30.5-40.5) in discharged patients and 39.0

Table 1

The main characteristics of the study population (n = 102) Characteristic Value

Age (y)	73 (64-79)
Sex (male)	78 (76.5%)
Medical history Diabetes mellitus	29 (28.4%)
Hypertension	30 (29.4%)
Coronary artery disease	34 (33.3%)
Heart failure	30 (29.4%)
Clinical characteristics Temperature (?C)	36.7 (36.5-37.2)

Heart rate (beats/min) 98 (86.8-114.0)

Respiratory rate (breaths/min) 20 (16-25)

SpO₂ (%) 84 (78-90)

Systolic arterial pressure (mm Hg) 130 (110-145)

Diastolic arterial pressure (mm Hg) 80 (70-80)

interquartile ranges. Bland-Altman analysis was used to determine

Number of patients admitted to ICU within one year

18 (17.6%)

the agreement between ETCO₂ and pCO₂ levels. The categorical data

were analyzed for significance by using the Pearson ?² test, where P b

Number of patients who were mechanically ventilated within one year

14 (13.7%)

.05 was considered to be statistically significant.

Values are presented as n (%) or median (interquartile range).

410 N.O. Dogan et al. / American Journal of Emergency Medicine 32 (2014) 408-411

Table 2

Results of arterial blood gas analysis parameters and ETCO₂ measurement regarding admission status

	Discharged patients,	Admitted patients,	P		All patients,
	median (IQR)	median (IQR)			median (IQR)
pH	7.39 (7.34-7.46)	7.38 (7.32-7.45)		0.636	7.39 (7.34-7.45)
pO₂ (mm Hg)	63.6 (43.6-79.2)	46.1 (37.7-62.5)		0.011	49.1 (42.0-66.3)
pCO₂ (mm Hg)	36 (31.8-49.4)	46.2 (39.3-54.7)	b	0.001	43.1 (35.3-51.0)
HCO₃ (mEq/L)	23.2 (21.8-26.7)	26.8 (22.8-28.0)		0.001	25.1 (22.4-27.2)
Lactate (mmol/L)	1.5 (1.3-1.6)	1.8 (1.3-2.1)	b	0.001	1.6 (1.3-1.9)
ETCO₂ (before treatment)	32.0 (30.5-40.5)	39.0 (31.0-53.5)		0.043	37.0 (31.0-45.5)
ETCO₂ (after treatment)	32.0 (28.0-37.5)	36.0 (32.0-52.0)		0.107	35.0 (30.0-44.0)

(31.0-53.5) in admitted patients. However, a statistically significant difference was observed in the pretreatment period (P = .043) (Fig. 2), and no difference was observed in the post-treatment period between ETCO₂ levels (P = .107). Also, regarding the admission status, no difference was observed between the pre-ETCO₂ (P = .720) and post-ETCO₂ (P = .233) levels.

A positive correlation was observed between pre-ETCO₂ and post-ETCO₂ levels (r = 0.791, P b .001). Pre-ETCO₂ and post-ETCO₂ levels were positively correlated with arterial pCO₂ levels (r = 0.756, P b .001 and r = 0.629, P b .001, respectively) and were negatively correlated with arterial pO₂ levels (r = -0.477, P b .001 and r = -0.358, P b .001). The Bland-Altman plot showed the mean bias +- SD between pre-ETCO₂ and pCO₂ as 4.68 +- 7.21 mm Hg (95% CI, 3.26-6.09), and the limits of agreement were -9.46 and

18.81 mm Hg (Fig. 3).

We constructed a receiver operating characteristic curve in order to determine the accuracy of ETCO₂ in predicting admission status, and the area under the curve for pre-ETCO₂ was 0.624 (95% CI, 0.515- 0.733) (P = .043) (Fig. 4). When the ETCO₂ level was taken as

34.5 mmHg, a sensitivity of 65.2% and a specificity of 63.6% were found, respectively.

Discussion

According to World Health Organization estimates, 65 million people have moderate to severe chronic obstructive pulmonary disease [12]. The disease was the fourth leading cause of death in the world, and acute exacerbations constitute a significant part of ED admissions [11]. As a particular population, COPD patients with exacerbation should be evaluated by arterial blood gas analysis in the ED, and the measurement of pCO₂ is a cornerstone for different Treatment decisions. There are several studies in the literature addressing the use of noninvasive end-tidal carbon dioxide measure-

ment in respiratory disturbances, and also involves the relationship between the ETCO₂ and pCO₂ levels in dyspneic patients. For patients with normal Respiratory function, the ETCO₂ values lie between 35 and 45 mmHg and a narrow ETCO₂-pCO₂ gradient (0-5 mmHg) due to alveolar dead space [6].

This study demonstrated that the ETCO₂ levels during an acute exacerbation of COPD are higher in admitted patients, when compared to the levels in discharged patients upon arrival to the ED. A pre-ETCO₂ level of 34.5 mmHg had a sensitivity of 65.2% in order to determine hospital admission. ETCO₂ levels were also strongly correlated with arterial pCO₂ levels in our study population. ETCO₂ measurement, as an alternative to arterial blood gas analysis in dyspneic patients still remains controversial. Although some studies have reported a statistical correlation and agreement between ETCO₂ and pCO₂ levels in patients with respiratory distress [8,9,13], some authors argue that the measurements did not agree well enough with the different levels of pCO₂ for the one method so as to replace the other using the Bland and Altman method [6,7,10,14]. The present study did not aim to investigate the possibility of replacing pCO₂ with ETCO₂; however, the results confirm the correlation between the 2 variables (r = 0.756 on arrival to the ED and r = 0.629 in the post- treatment). Cinar et al investigated whether the mainstream ETCO₂ measurement can accurately predict the PCO₂ level of the patients presented to the ED with acute dyspnea. They found a strong correlation (r = 0.911) and agreement (0.5 +- 5 mm Hg, 95% CI - 10.5 and +9.5 mm Hg) between the ETCO₂ and PCO₂ levels [8]. Also, Kartal et al demonstrated a moderate correlation between two variables, but they also concluded that poor agreement between the two variables exists (8.4 mm Hg) [6]. The present study demonstrated a mean bias of 4.68 +- 7.21 using the Bland-Altman plot, which limits the utilization of ETCO₂ in COPD exacerbations, although a significant correlation exists between 2 variables.

Fig. 2. Admission status of patients and alteration of ETCO₂ levels. Fig. 3. Agreement between pCO₂ and ETCO₂ values (Bland-Altman plot).

N.O. Dogan et al. / American Journal of Emergency Medicine 32 (2014) 408-411 411

Fig. 4. ROC curve.

Regarding our results, arterial blood gas analysis revealed the expected alterations in discharged and admitted patients. Although, pre-ETCO₂ levels were significantly higher in admitted patients when compared to the levels in discharged patients (similar to pCO₂), crossing the confidence intervals makes it difficult to evaluate ETCO₂ levels as a Prognostic tool in COPD exacerbations. The limited sensitivity and specificity of ETCO₂ prompt the use of arterial blood gas analysis rather than the mainstream measurement of ETCO₂. Accordingly, the measurement of ETCO₂ may be helpful in pre- hospital settings in order to determine the need for hospital admission instead of the EDs.

Langhan et al carried out a similar study in children with acute exacerbations of asthma. They hypothesized that the quantitative ETCO₂ levels will be lower in children during an acute exacerbation of asthma and will correlate with the severity of the exacerbation. In this study, ETCO₂ was significantly lower in patients with acute exacer- bation of asthma when compared with the Control subjects. Moreover, end-tidal carbon dioxide was measured after the first and after the final bronchodilator treatment was significantly associated with hospital admission [15]. In our study, COPD patients with severe exacerbations were admitted to hospital and the initial ETCO₂ levels were observed to be higher in those patients. These levels were also found to be concordant with pCO2 levels in arterial blood gas analysis. After the first bronchodilator treatment was completed, no difference

between the ETCO₂ levels was observed in the discharged and Admitted groups.

The present study has several limitations. First, the sample size for admitted and discharged patients was relatively small, and this was undertaken at a single center, which limits the generalization of our findings to other settings. Second, we only measured the ETCO₂ with a portable mainstream capnometer by asking patients to breathe through the tube. This might cause the misinterpretation of results in those patients who have difficulties when breathing through the capnometer. The third main limitation was that pCO₂ values were not corrected to account for temperature.

In conclusion, the end-tidal carbon dioxide levels were higher in patients with severe Exacerbations of COPD. This information may be useful in a pre-hospital setting to determine the noninvasive mechanical ventilation or the hospital admission need; however, ETCO₂ measurement gives very little contribution while evaluating patients with COPD exacerbation in the ED.

References

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