ABSTRACT

Objective:

This study aims to compare the effectiveness of non-invasive pressure of transcutaneous CO₂ (PtcCO₂) and O₂ (PtcO₂) analyzers versus conventional blood gas sampling in patients with sepsis and septic shock.

Materials and Methods:

Sepsis patients without a need for inotrope support (sepsis) were prospectively enrolled to group 1 (n=50), whereas group 2 (n=50) was composed of patients needing inotropes (septic shock). Demographic data, laboratory tests, Acute Physiology and Chronic Health Evaluation-II (APACHE-II) and Sequential Organ Failure Assessment (SOFA) scores, standard monitoring data, data of blood gas analysis (pH, PaCO₂, PaO₂, and SaO₂), and transcutaneous CO₂ and O₂ were collected at the first, second, third, and fourth hours.

Results:

No significant difference was noted between the groups in terms of demographic parameters, baseline white blood cell, hematocrit, baseline heart rate, central venous pressure, respiratory rate, and positive end-expiratory pressure values. Group 2 had significantly higher serum urea and creatinine levels and lower albumin levels and mean arterial pressure, whereas group 1 had significantly lower APACHE-II and SOFA scores and peak inspiratory pressure and FiO₂.

No significant difference was noted between the PtcCO₂ and PaCO₂ values in group 1, whereas the PtcCO₂ values of group 2 were significantly lower than PaCO₂. PtcO₂ and PaO₂ values were significantly lower in group 1, whereas PtcO₂ vs PaO₂ values were significantly lower in group 2. A strong correlation was noted between arterial and transcutaneous CO₂ and O₂ values in both the groups.

Conclusion:

PtcCO₂ assessment may be an alternative method in patients with sepsis but not in septic shock. PtcO₂ measurement may not be a reliable method for patients with sepsis and septic shock.

Keywords: Sepsis, septic shock, ICU, transcutaneous CO2, transcutaneous O2, arterial blood gas analysis

Introduction

Sepsis is one of the leading causes of mortality and morbidity and has great clinical importance in general intensive care units (ICUs) in adults. Microcirculatory perfusion fails due to various mechanisms related to sepsis, which impairs measurement and assessment of peripheral oxygen saturation (SpO₂). Analysis of arterial blood samples is known as “gold standard” method to evaluate systemic oxygenation in septic patients (1,2).

However, the method used in routine clinical practice is invasive, expensive, painful and time-consuming. Manufacturers are also willing to introduce advanced non-invasive oxygenation monitoring devices and techniques. Nevertheless, the accuracies of these novel devices in different clinical situations are debated and have not been extensively studied.

To our knowledge this is one of the pioneering prospective studies in the literature comparing the transcutaneous O₂ and CO₂ analysis versus arterial blood gas analysis in septic patients in ICU. The aim of the study is to compare the effectiveness of non-invasive pressure of transcutaneous CO₂ (PtcCO₂) and O₂ (PtcO₂) analyzers versus conventional blood gas sampling in patients with sepsis and septic shock.

Materials and Methods

Approval of the study has been obtained from the Clinical Research Ethics Committee of the Gaziantep University (decision no: 249, date: 20.12.2011). A hundred patients, who have been admitted to the ICU with a diagnosis of sepsis or septic shock, were enrolled to the study. All the patients and/or their relatives were informed verbally and also written consent were obtained.

Patients, who are under 18 years old or have body mass indices (BMI) >35 or <18 kg/m², were excluded from the study. Patients diagnosed with sepsis were divided into two study groups. Sepsis patients without a need for inotrope support (sepsis) were enrolled to group 1 (n=50), and group 2 (n=50) was composed of sepsis patients with a need for inotropes (septic shock). Diagnosis of sepsis and septic shock were made according to classical criteria (3).

Demographic data of the patients (including age, gender, BMI), baseline white blood cell (WBC) count, hematocrit (Hct), serum urea, creatinine, albumin levels, Acute Physiology and Chronic Health Evaluation-II (APACHE-II) and Sequential Organ Failure Assessment (SOFA) scores were recorded.

Heart rate, mean arterial pressure (MAP), central venous pressure (CVP), oxygen saturation (SaO₂), respiratory rate, peak inspiratory pressure (PIP), positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO₂) values were also simultaneously recorded.

Body temperature was continuously monitored and recorded.

Radial artery was cannulated for blood gas analysis and procedure lasted for approximately 5 minutes. Blood samples for blood gas analysis were collected at the 1^st, 2^nd, 3^rd, and 4^th hours and pH, PaCO₂, PaO₂, SaO₂ were analysed with Cobas b 121™ (Mennheim, Germany).

PtcO₂ and PtcCO₂ were measured with Transcutaneous Combi M4 (TCM4)™ (Radiometer^®, Copenhagen, Denmark) and were recorded simultaneously with the arterial blood sampling. Device was calibrated before inserting the transcutaneous blood gas probe in every patient. If unexpected alterations of recorded values were noticed, bio calibration was repeated. Conventionally, temperature of the electrode of TCM4™ was set to 43 °C. The electrode of the TCM4™ was put on a hairless area of the forearm using a sticky fixation ring (E 5260/E 5280: Fixation ring 904-891; 30 mm; Radiometer Medical ApS, Denmark) at the opposite side of the arm that arterial blood samples were obtained. A few beads of electrolyte solution (Electrolyte solution, Radiometer Medical ApS, Denmark) were dropped to establish a contact between the electrode and the skin. The localization of the electrodes remained constant during the study.

Inotropic indices of the patients in group 2 were calculated according to the following formula depending on the vasoactive drug(s) used: Inotropic index = Dopamine* + Dobutamine* + (100x Epinephrine*) + (100x Norepinephrine*) + (15x Milrinone*)(4).

(*µg/kg/min infusion rate)

Statistical Analysis

The normality of distribution of continuous variables was tested by Kolmogorov-Smirnov test. Student’s t-test was used for comparison of two independent groups of variables with a normal distribution and Mann-Whitney U test was used when the distribution was not normal. Paired t-test was utilized for comparison of two dependent groups of variables with normal distribution and Wilcoxon test was preferred when the distribution was not normal. The chi-square test was used to assess relation between categorical variables and Pearson correlation coefficient was utilized for assessing relation between continuous variables. Descriptive statistic parameters were presented as frequency, percentage (%) and mean ± standard deviation. Statistical analysis was performed with SPSS for Windows version 11.5^® and a p-value <0.05 was accepted as statistically significant.

Results

A hundred patients were enrolled to the study. Female to male ratios of group 1 and 2 were 24/26 and 25/25, respectively (p=0.841). Mean age of the patients in group 1 and 2 were 53.72±20.39 and 54.18±20.26, respectively (p=0.911). Also, BMI values of the patients in group 1 and 2 were 25.55±3.15 kg/m² and 25.05±3.10 kg/m², respectively (p=0.423).

There was no significant difference between groups in terms of baseline WBC (19062±13913/mm³ vs 19492±9573/mm³; p=0.857) and Hct (30.94±5.77% vs 31.66±6.40%; p=0.556). Serum urea (80.16±49.75 mg/dL vs 122.54±71.89 mg/dL; p=0.003) and creatinine (1.42±1.32 mg/dL vs 2.38±1.70 mg/dL; p=0.001) levels were significantly higher, whereas albumin levels (2.94±0.47 g/dL vs 2.68±0.49 g/dL; p=0.008) were lower in group 2. APACHE-II (28.26±4.84 vs 33.94±5.20; p=0.001) and SOFA (8.02±2.13 vs 10.64±2.53; p=0.001) scores were significantly lower in group 1.

Baseline heart rate (114.78±29.84 bpm vs 120.90±24.47 bpm; p=0.265) and CVP (3.96±2.81 cmH₂O vs 3.32±2.97 cmH₂O; p=0.272) values were not significantly different between the groups. Baseline MAP was significantly decreased in group 2 compared with group 1 (96.94±22.18 mmHg vs 76.36±17.49 mmHg; p=0.001).

There was no significant difference between groups in terms of body temperature (37.12±1.03 °C vs 37.09±1.42 °C; p=0.806).

Comparison of baseline respiratory rate (20.98±6.98/min vs 21.24±5.79/min; p=0.840) and PEEP (6.30±1.79 cmH₂O vs 6.76±2.03 cmH₂O; p=0.231) values was not statistically different between two groups. However, baseline PIP (15.34±5.03 cmH₂O vs 18.64±5.73 cmH₂O; p=0.003) and FiO₂ (0.502±0.19 vs 0.625±0.21; p=0.003) values were significantly decreased in group 1.

The pH values of patients in group I were significantly higher than group 2 at the baseline (7.41±0.08 vs 7.34±0.15, p=0.005), 1^sthour (7.41±0.07 vs 7.34±0.15, p=0.004), 2^ndhour (7.41±0.07 vs 7.34±0.14, p=0.004), 3^rd hour (7.41±0.07 vs 7.34±0.14, p=0.004) and 4^thhour (7.40±0.07 vs 7.34±0.14, p=0.003).

There was no significant difference between PtcCO₂ and PaCO₂ values analyzed simultaneously at baseline, 1^st, 2^nd, 3^rd and 4^th hours in group 1 (Table 1).

Table 1

PtcCO₂ values of group 2 were significantly lower when compared with PaCO₂ at baseline, 1^st, 2^nd, 3^rd and 4^th hours (Table 2).

Table 2

PtcO₂ versus PaO₂ values were significantly lower in group 1 at baseline, 1^st, 2^nd, 3^rd and 4^th hours (Table 3).

Table 3

PtcO₂ vs PaO₂values were significantly lower in group 2 at baseline, 1^st, 2^nd, 3^rd and 4^th hours (Table 4).

Table 4

There was a statistically strong positive correlation between arterial and transcutaneous CO₂ values in group 1 at the baseline (r=0.972, p=0.001), 1^st(r=0.971, p=0.001), 2^nd(r=0.982, p=0.001), 3^rd (r=0.986, p=0.001) and 4^th(r=0.988, p=0.001) hours. There was a statistically similar strong positive correlation between arterial and transcutaneous CO₂ values in group 2 at the baseline (r=0.983, p=0.001), 1^st(r=0.976, p=0.001), 2^nd(r=0.981, p=0.001), 3^rd (r=0.981, p=0.001) and 4^th(r=0.982, p=0.001) hours. Correlation between PtcCO₂ ve PaCO₂ alterations in group 1 and group 2 are shown on Figure 1.

Figure 1

Correlation analysis of arterial and transcutaneous O₂ values in group 1 was performed and a statistically strong positive correlation was revealed at the baseline (r=0.815, p=0.001), 1^st(r=0,881, p=0.001), 2^nd(r=0.890, p=0.001), 3^rd (r=0.863, p=0.001) and 4^th(r=0.882, p=0.001) hours. A similar statistically strong positive correlation between arterial and transcutaneous O₂ values in group 2 was observed at the baseline (r=0.826, p=0.001), 1^st(r=0.827, p=0.001), 2^nd(r=0.659, p=0.001), 3^rd (r=0.838, p=0.001) and 4^th(r=0.834, p=0.001) hours. Correlation between PtcCO₂ ve PaCO₂ alterations in group 1 and group 2 are shown on Figure 2.

Figure 2

Inotropic index was 25.54±13.92 in group 2.

Discussion

Septic patients have compromised tissue perfusion due to microcirculatory disturbances. Impaired tissue microperfusion of patients with septic shock had been clearly shown in previous studies. In general, macro circulatory parameters are the main targets in order to optimize treatment of septic shock in early phase (5). However, persistent compromisation of tissue perfusion may occur in some patients due to microcirculatory disturbances. Although conventional blood gas sampling methods are considered as “gold standard”, there is always place for a less invasive, painless, and timesaving “patient-friendly” alternatives. There are many papers implicating the cons of unnecessary blood draws with respect to not only anemia but also infection control and healthcare costs (6,7). Therefore the need for less invasive monitoring methods is evident.

In the English literature there are recent papers regarding comparison between non-invasive PtcO₂/PtcCO₂ monitoring and conventional blood gas sampling methods such as in neonatal and adult ICUs (8-10), but to the best of our knowledge this is the first prospective study comparing the transcutaneous O₂ and CO₂ analysis versus arterial blood gas analysis in a homogenous specific subgroup such as septic patients in ICU and also one of the largest sample size.

There are three major results arising from this study. First, there was no significant difference between the values of PtcCO₂ and PaCO₂ in patients with sepsis. There was a strong positive correlation between PtcCO₂ and PaCO₂ values (Figure 1). These findings may support to use PtcCO₂ monitoring as an acceptable alternative method.

Second, PtcCO₂ values of group 2 were significantly lower than PaCO₂ values (p<0.05) and there was a strong positive correlation between the values indeed. This finding is not surprising because abolished peripheral microcirculation is a part of the septic shock pathophysiology itself. Hypo perfusion states like shock and/or acidosis may present decreased values of PtcO₂and PtcCO₂and vasoactive drug administration may also result in decreased PtcO₂ and PtcCO₂(11-14).

Recent TCM™ devices with the help of selection of a sensor place near the carotid artery have led to improved correlation between PaO₂ and PtcO₂measurements (15-18). Studies regarding placement of the sensor site on the distal part of an extremity have reported lower readings, due to vasoconstriction limiting blood flow (19-21). Other studies have shown that choosing a sensor area in chest, infraclavicular area or ear is accompanied with more reliable results (22,23). In this present study, the sensor was placed in the forearm, which can be accepted relatively a distal part of the extremity, and therefore might have contributed to the lower reading of PtcCO₂ values in patients with septic shock. Although we demonstrated strong positive correlation between simultaneously obtained PtcCO₂and PaCO₂ values, this may be accepted as a limitation of the study. This unexpected finding of our study also emphasizes the importance of correct selection of sensor electrode placement, especially when the pathophysiology of septic shock is considered.

Third, simultaneously measured values of PtcO₂ were significantly lower than PaO₂and there were strong positive correlations in both study groups. This finding is consistent with the literature. The more the skin is warmed to highest tolerable temperature, the more increase takes place in the capillary blood flow. In order to reach the greatest increased blood flow, the highest tolerable temperature is reported as 45 °C, when the surface blood PtcO₂ rises to approximately PaO₂ (24). There is a generally accepted rule for safety as limiting the electrode temperature at 43 °C up to four hours, although suggested monitoring method for detection of PtcCO₂ and PtcO₂ is to increase the skin temperature up to 45 °C to arterialize capillary blood flow (25,26). However, higher electrode temperatures may generate the risk of skin burning. In our study, we limited the electrode temperature at 43 °C for safety, which is appropriate for detecting PtcCO₂, but not for PtcO₂. Our concerns regarding safety instead of increasing the temperature of the electrodes for more accurate measurements seems to be another dilemma when interpreting our results.

Another explanation for the lower detected values of PtcO₂ in both groups may be impaired macro and microcirculation, which is similar to PtcCO₂.

Conclusion

In summary, transcutaneous monitoring of CO₂ may be a charming, less-invasive, time-consuming and reliable alternative method in patients with sepsis. The effectiveness and safety of this method in patients with septic shock is questionable. Transcutaneous monitoring of O₂ may not be a reliable and feasible method for patients with sepsis and septic shock. The need for further large scaled studies is evident to confirm the safety, effectiveness and optimization of these recent techniques of transcutaneous CO₂ and O₂ monitoring.

Ethics

Ethics Committee Approval: Approval of the study has been obtained from the Clinical Research Ethics Committee of the Gaziantep University (decision no: 249, date: 20.12.2011).

Informed Consent: All the patients and/or their relatives were informed verbally and also written consent were obtained.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: R.S., B.K.U., Concept: R.S., B.K.U., S.G., Design: R.S., S.G., Data Collection and Process: R.S., S.G., P.T., Analysis or Interpretation: B.K.U., S.G., Literature Search: B.K.U., P.T., Writing: B.K.U.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: Financial support was received from Gaziantep University Rectorate Scientific Research Projects Department for this study (project no: TF.12.33).

References

Awasthi S, Rani R, Malviya D. Peripheral venous blood gas analysis: An alternative to arterial blood gas analysis for initial assessment and resuscitation in emergency and intensive care unit patients. Anesth Essays Res 2013;7:355-8.

Quinn LM, Hamnett N, Wilkin R, Sheikh A. Arterial blood gas analysers: accuracy in determining haemoglobin, glucose and electrolyte concentrations in critically ill adult patients. Br J Biomed Sci 2013;70:97-100.

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med 2017;43:304-77.

Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 1995;92:2226-35.

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.

Ullman AJ, Keogh S, Coyer F, Long DA, New K, Rickard CM. ‘True Blood’ The Critical Care Story: An audit of blood sampling practice across three adult, paediatric and neonatal intensive care settings. Aust Crit Care 2016;29:90-5.

Gray R, Baldwin F. Targeting blood tests in the ICU may lead to a significant cost reduction. Crit Care 2014;18(Suppl 1):P15.

Urbano J, Cruzado V, López-Herce J, del Castillo J, Bellón JM, Carrillo A. Accuracy of three transcutaneous carbon dioxide monitors in critically ill children. Pediatr Pulmonol 2010;45:481-6.

Spelten O, Fiedler F, Schier R, Wetsch WA, Hinkelbein J. Transcutaneous PTCCO2 measurement in combination with arterial blood gas analysis provides superior accuracy and reliability in ICU patients. J Clin Monit Comput 2017;31:153-8.

Rodriguez P, Lellouche F, Aboab J, Buisson CB, Brochard L. Transcutaneous arterial carbon dioxide pressure monitoring in critically ill adult patients. Intensive Care Med 2006;32:309-12.

Shoemaker WC, Wo CC, Lu K, Chien LC, Rhee P, Bayard D, et al. Noninvasive hemodynamic monitoring for combat casualties. Mil Med 2006;171:813-20.

Yu M, Morita SY, Daniel SR, Chapital A, Waxman K, Severino R. Transcutaneous pressure of oxygen: a noninvasive and early detector of peripheral shock and outcome. Shock 2006;26:450-6.

Weaver LK. Transcutaneous oxygen and carbon dioxide tensions compared to arterial blood gases in normals. Respir Care 200;52:1490-6.

Lang CJ. Apnea testing guided by continuous transcutaneous monitoring of partial pressure of carbon dioxide. Crit Care Med 1998;26:868-72.

Bendjelid K, Schütz N, Stotz M, Gerard I, Suter PM, Romand JA. Transcutaneous PCO2 monitoring in critically ill adults: clinical evaluation of a new sensor. Crit Care Med 2005;33:2203-6.

Senn O, Clarenbach CF, Kaplan V, Maggiorini M, Bloch KE. Monitoring carbon dioxide tension and arterial oxygen saturation by a single earlobe sensor in patients with critical illness or sleep apnea. Chest 2005;128:1291-6.

Berkenbosch JW, Lam J, Burd RS, Tobias JD. Noninvasive monitoring of carbon dioxide during mechanical ventilation in older children: end-tidal versus transcutaneous techniques. Anesth Analg 2001;92:1427-31.

Vivien B, Marmion F, Roche S, Devilliers C, Langeron O, Coriat P, et al. An evaluation of transcutaneous carbon dioxide partial pressure monitoring during apnea testing in brain-dead patients. Anesthesiology 2006;104:701-7.

Tobias JD. Transcutaneous carbon dioxide monitoring in infants and children. Paediatr Anaesth 2009;19:434-44.

Huch R, Huch A, Albani M, Gabriel M, Schulte FJ, Wolf H, et al. Transcutaneous PO2 monitoring in routine management of infants and children with cardiorespiratory problems. Pediatrics 1976;57:681-90.

Nishiyama T, Nakamura S, Yamashita K. Comparison of the transcutaneous oxygen and carbon dioxide tension in different electrode locations during general anaesthesia. Eur J Anaesthesiol 2006;23:1049-54.

Nishiyama T, Kohno Y, Koishi K. Comparison of ear and chest probes in transcutaneous carbon dioxide pressure measurements during general anesthesia in adults. J Clin Monit Comput 2011;25:323-8.

Baumberger JP, Goodfriend RB. Determination of arterial oxygen tension in man by equilibration through intact skin. Fed Proc;1951;10:10 (abs).

Nishiyama T, Nakamura S, Yamashita K. Effects of the electrode temperature of a new monitor, TCM4, on the measurement of transcutaneous oxygen and carbon dioxide tension. J Anesth 2006;20:331-4.

Sørensen LC, Brage-Andersen L, Greisen G. Effects of the transcutaneous electrode temperature on the accuracy of transcutaneous carbon dioxide tension. Scand J Clin Lab Invest 2011;71:548-52.

Comparison of Transcutaneous and Arterial Blood Gas Analyses in Patients with Sepsis and Septic Shock