Can End-tidal Carbon Dioxide Levels Be Used for Determining Tissue Oxygen Saturation in Smokers and Nonsmokers?

Objectives: End-tidal carbon dioxide (EtCO2) monitoring has been used in a range areas, such as invasive sedation procedures, during cardiopulmonary resuscitation, ventilation monitoring of patients with altered mental status, trauma and respiratory system diseases in emergency departments. Near-infrared spectroscopy (NIRS) allows continuous, noninvasive measurement of tissue hemoglobin oxygen saturation (StO2) in muscle and has been studied for a wide range of conditions. In this study we aim to determine the levels of EtCO2 and StO2 in smokers and nonsmokers and the relationship between these two parameters. Methods: We examined 201 healthy volunteers including 156 smokers and 45 nonsmokers. We measured thenar muscle StO2 via NIRS device. The EtCO2 was determined by a capnograph. Baseline measurements were obtained from all participants after not-smoking for two h. Second measurements were taken 5 min after smoking was finished. Results: The mean baseline EtCO2 of the smoker group was 42.61±4,94 (min:31, max:54) mmHg and mean baseline StO2 for this group was 77.81±4.71% (min:69, max:86). In smokers, mean baseline EtCO2 (p:0.00), baseline StO2 (p:0.001), fifth min EtCO2 (p:0.00), fifth min StO2 (p:0.02) levels, and pack*year (p:0.00) were significantly different between males and females. In nonsmokers baseline EtCO2 and baseline StO2 levels were correlated (p:0.035,r:0.315). But we couldn’t find significance between females and males for mean baseline EtCO2 (p:0,246) and baseline StO2 (p:0.264) levels in this group. Conclusion: Smoking affects tissue oxygenation. In nonsmokers baseline EtCO2 and baseline STO2 levels were correlated, but there was no correlation for these two parameters in smokers. Clinicians may use EtCO2 levels for predicting the tissue oxygenation in nonsmoker patients.


INTRODUCTION
Capnograph was originally used for validation of endotracheal tube placement during cardiopulmonary resuscitation (CPR) studies in emergency practice [1,2]. But during recent years, end-tidal carbon dioxide (EtCO2) monitoring via capnograph has been used in a range of areas such as invasive sedation procedures, cardiopulmonary resuscitation effectivity, ventilation monitoring of patients with altered mental status, trauma and respiratory system diseases [3][4][5][6][7].
Near-infrared spectroscopy (NIRS) allows continuous, noninvasive measurement of tissue hemoglobin oxygen saturation (StO2) in muscle and has been studied in a wide range of conditions [8]. NIRS has been used in critically ill patients especially in intensive care units (ICUs) and also researches have still been studying the efficiacy and areas of use of this device [9]. It has also been used to classify the severity of hemorrhagic shock, as a guide for fluid resuscitation, and during elective surgery septic shock, multiple -organ dysfunction syndrome and as a vital sign prehospitally [10][11][12][13][14][15][16].
In this study we aim to determine the levels of EtCO2 and StO2 in smokers and nonsmokers and the relationship between these two parameters and besides whether EtCO2 levels may help clinicans to predict the StO2 levels in smoker and nonsmoker patients.

METHOD Subjects
We examined 201 healthy volunteers: 156 smokers and 45 nonsmokers. Participants with chronic or acute diseases, history of drug usage, pregnant women and volunteers under 18 years of age were excluded from the study.

StO2
In our study, we measured thenar muscle StO2 via widegap second-derivative NIRS (InSpectra; Hutchinson Technology). This device serves to predict the hemoglobin Sto2 in the microvasculature of muscle tissue, including the arteriolar, capillary and venular compartments [17].

EtCO2
EtCO2 was determined by the EMMA capnograph (Masimo Sweden AB), which measures end-tidal pressure by means of an infrared-absorbing sensor. We also used an EMMA airway adaptor and 7.0 endotracheal tube to evaluate the expiratuar breathing.

Experimental Protocol
Our study was approved by the Human Study Committee of our medical faculty (10.04.2014/43). The volunteers were informed and gave their informed consent. All measurements took place in a temperature-controlled environment. The study group was comfortably seated and breathing normally before, during and after the measurement. Smokers had been instructed to refrain from smoking for at least 2 h prior to the measurements. Baseline measurements were obtained from all participants. Smokers were then asked to smoke a cigarette according to their habitual brand, maintaining the usual aspiration pattern. Second measurements were taken 5 min after smoking was finished. Each participant held the endotracheal tube placed to the airway adapter of the capnograph in his or her mouth and expirated for 5 seconds. The last values on the screen were recorded before and after smoking. Similarly, for the StO2 levels, an Inspectra device was placed to the right thenar muscle for 10 s and mean of the first, fifth and 10th second values were noted.

Statistical Analysis
The normal distribution and homogeneity of each parameter were tested using the Shapiro-Wilk test and the Kolmogorov-Smirnov test. Age, gender, baseline ETCO2, baseline STO2, fifth min Etco2 and fifth min StO2 values did not suit the normal distribution. A Mann Whitney-U test was used for differences between and among two groups. A Spearman correlation test was used for correlation analysis. In all tests the significance level was p<0.05. SPSS (Statistical Package for the Social Sciences) software 18.0 was used for allanalysis.

DISCUSSION
In our study, baseline STO2 levels of smokers were higher than those of nonsmokers, but ETCO2 values didn't differ. In nonsmokers baseline EtCO2 and baseline StO2 levels were correlated. But there was no correlation for these two parameters in smokers.
In the literature, there have been several studies on the use of emergency EtCO2 monitoring. Wahlen et al's study investigated EtCO2 values in spontaneously breathing patients. They searched for the influence of EtCO2 monitoring on therapeutic decisions by emergency physicians. Their study included 299 patients were included and reported pathological EtCO2 values in 19 patients (6.3%). They suggested that EtCO2 monitoring may be a useful additional variable in spontaneously breathing patients [17].
Another study examined the relationship among EtCO2 and other oxygenation markers such as arterial oxygen pressure (PaO2), carbon dioxide pressure (PaCO2), and pulse oximetry (SpO2). Giner performed this study in 57 active smokers. In this study, the mean SpO2 of the participants was 95%, and oxygen saturation measured directly in arterial blood samples was 95.1%. The mean EtCO2 was 37.9 mm Hg and PaCO2 by arterial blood gas analysis was 40.6 mm Hg. They found a correlation between EtCO2-SpO2 and EtCO2-PaCO2. Although this suggested that both oxyhemoglobin saturation assessments and both CO2 pressure determinations were closely related, it cannot be inferred that the 2 techniques in each case are completely congruent. Pulse oximetry and capnography are both useful for monitoring oxyhemoglobin saturation or ventilation [18].
In a recent study, StO2 monitoring for acute effects of smoking has been reported by Siafaka et al. Similarly to our study, they used NIRS to compare the microcirculatory function of smokers with that of nonsmokers. They studied 25 smokers and 40 nonsmokers, but their study protocol was different from ours except for its measurement times and measurement area (thenar region). They asked the participants not to smoke for 2h beforel the baseline measurement and took the last measurement after 5 min too. But they preferred a continious StO2 monitoring. They recorded StO2 baseline values for 5 min. Subsequently, the brachial artery occlusion technique was applied to evaluate microcirculatory function before, during, and after smoking a cigarette. In that study, StO2 before smoking was 85, which did not differ significantly between genders and StO2 did not change significantly during smoking. O2 consumption rate was significantly greater in women at baseline and throughout the smoking session. O2 consumption rate was reduced during smoking and at 5 min after the smoking session. Smoking had a significant effect on vascular reactivity, with no significant differences between genders. Five minutes after smoking, vascular reactivity had returned to approximately normal levels [19].
In another study, Terborg et al searched for cerebral blood flow and oxygenation in 24 healthy volunteers via transcranial Doppler sonography and near-infrared spectroscopy before, during, and after smoking a cigarette. They simultaneously recorded cerebral blood flow velocity of both middle cerebral arteries, mean arterial blood pressure, skin blood flow, EtCO2, changes in concentration of cerebral oxyhemoglobin, deoxyhemoglobin, and total hemoglobin, and a cerebral tissue oxygenation index. Smoking increased cerebral blood flow velocity, oxyhemoglobin, and total hemoglobin. After smoking, the increase in cerebral blood flow velocity and total hemoglobin persisted, while oxyhemoglobin returned to baseline. Deoxyhemoglobin and cerebral tissue oxygenation index did not change during the whole procedure. During smoking, but not after, cerebral blood flow velocity increase was correlated to ipsilateral changes in oxyhemoglobin and total hemoglobin. In this study, tissue oxygenation index was 64.6% before smoking, 65.5% during smoking, and 64.6% after smoking. Mean EtCO2 was 41.4 mmHg and 40.2 mmHg after smoking [20].
Akca et al examined brain tissue oxygenation and EtCO2 monitoring in 20 surgical patients to determine the postoperative infection risk. In this study, the patients underwent intraoperative EtCO2, tissue oxygen partial pressure, transcutaneous oxygen tension and cerebral oxygen saturation monitoring via cerebral oximeter. The authors reported that mild intraoperative hypercapnia increased subcutaneous and cerebral oxygenation [21].
www.jceionline.org CONCLUSION In our study, baseline StO2 levels of smokers were higher than those of nonsmokers, but EtCO2 values did not differ. As a result of this, we can say that smoking affects tissue oxygenation. In nonsmokers, baseline EtCO2 and baseline StO2 levels were correlated, but there was no correlation for these two parameters in smokers. EtCO2 measurement devices are much more easy to reach and cheaper when compared with near infrared spectroscope both in emergency departments and intensive care units. These results indicate that EtCO2 levels of nonsmoker patients may help clinicans to predict the StO2 levels.
Because of lack of literature, further comprehensive studies are needed to explain the reasons for these changes in acute and long term smoking the use of these parameters especially the StO2 in the ED.