Transcutaneous carbon dioxide measurements in patients undergoing retroperitoneoscopic urologic surgery: A prospective observational study

doi:10.21203/rs.3.rs-2576714/v1

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Transcutaneous carbon dioxide measurements in patients undergoing retroperitoneoscopic urologic surgery: A prospective observational study

https://doi.org/10.21203/rs.3.rs-2576714/v1

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Purpose: The aim of the current study was to investigate the accuracy of transcutaneous CO₂ pressure (P_TCCO₂) monitoring and the correlation between it and arterial CO₂ pressure (P_aCO₂), so as to determine P_aCO₂ in patients undergoing retroperitoneoscopic urologic surgery.

Methods: 50 patients undergoing retroperitoneoscopic urologic surgery were enrolled in this study. P_aCO₂, end-tidal carbon dioxide partial pressure (P_ETCO₂), and P_TCCO₂values were measured at 4 time points: before pneumoperitoneum, 30 mins, 60 mins and 90 mins after pneumoperitoneum, respectively. The differences of P_aCO₂–P_ETCO₂ and P_aCO₂- P_TCCO₂ were calculated. Paired t test, Bland–Altman method, correlation and regression analysis, as well as Fisher’s exact test were employed for the data analysis.

Results: Totally 157 samples were obtained. The mean (SD) of P_aCO₂, P_ETCO₂ and P_TCCO₂were 55.5 (7.2) mmHg, 42.3 (5.2) mmHg and 51.9 (84) mmHg, respectively. The absolute difference of P_aCO₂－P_ETCO₂ was 13.20 ± 4.43 mmHg and 4.35 ± 2.56 mmHg for P_aCO₂－P_TCCO₂ (P < 0.0001). And the correlation coefficient (r) between P_aCO₂ and P_ETCO₂was 0.79 (r²= 0.62, P < 0.0001) , whereas that value between P_aCO₂ and P_TCCO₂ was 0.91 (r² = 0.83, P < 0.0001). Meanwhile, the linear regression between P_aCO₂and P_ETCO₂ was P_ETCO₂ = 0.60×P_aCO₂＋9.10 (P < 0.0001), whilst the counterpart between P_aCO₂ and P_TCCO₂ was P_TCCO₂ = 1.07×P_aCO₂－7.30 (P < 0.0001). The 95% limits of agreement (LOA) of P_aCO₂versus P_ETCO₂ was 4.53 to 21.88 mmHg and -3.18 to 10.48 mmHg for P_aCO₂versus P_TCCO₂.

Conclusion: P_TCCO₂ monitoring provided greater accuracy to estimate P_aCO₂in patients undergoing retroperitoneoscopic urologic surgery as compared to P_ETCO₂.

Transcutaneous carbon dioxide

Retroperitoneoscopic

Urologic surgery

Blood gas monitoring

End-tidal carbon dioxide

Retroperitoneal laparoscopic surgery is now a popular, practiced and widely-accepted technique of minimally invasive surgeries for most urologic tumors based on retroperitoneal carbon dioxide (CO₂) insufflation. However, the absorption of CO₂ remains controversial between intraperitoneal pneumoperitoneum and retroperitoneal pneumoperitoneum. Kadam PG et al [1] found that there had no obvious differences between laparoscopic and retroperitoneoscopic renal resection surgeries, while subcutaneous emphysema could increase CO₂ absorption significantly. Additionally, NG CS et al [2] thought retroperitoneoscopic surgery did not increase the absorption of CO₂, compared with laparoscopic renal or adrenal surgery. Contrary to Streich B et al [3] results, they found the absorption of CO₂ in retroperitoneoscopic urologic surgery was higher than that in laparoscopic surgery.

The end-tidal carbon dioxide partial pressure(P_ETCO₂)is a technique for noninvasive monitoring of CO₂, and is widely used in ventilated patients. But many factors can influence the accuracy of P_ETCO₂, such as ventilation to blood flow ratio (V/Q) imbalance, chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea hypopnea syndrome (OSAS), surgical positions and other cardiovascular diseases. Laparoscopy or retroperitoneoscopy and the insufflation may diminish the accuracy of P_ETCO₂ monitoring. Although arterial blood gas (ABG) analysis is the golden standard of monitoring arterial blood carbon dioxide partial pressure (P_aCO₂) currently, ABG analysis is invasive and incoherent. Frequent ABG analysis is also an important cause of iatrogenic anemia, especially in those critically ill and infant patients.

Another noninvasive monitoring of CO₂ partial pressure is transcutaneous carbon dioxide partial pressure (P_TCCO₂). This method has been widely accepted in obese patients and others, which can provide greater accuracy compared to P_ETCO₂ monitoring during laparoscopic surgery [4–6]. However, there is a lack of studies upon the accuracy of CO₂ partial pressure monitoring in retroperitoneoscopic surgeries. The aim of this study was to investigate the accuracy of different CO₂ partial pressure monitoring techniques and their correlations with arterial CO₂ pressure (P_aCO₂) in patients undergoing retroperitoneoscopic surgery.

This study was registered at www.ClinicalTrials.gov (registration number: NCT03226041). The protocol was approved by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (Nanjing, Jiangsu province, China). And a written consent was obtained from each of the 50 participants undergoing retroperitoneoscopic urologic surgery. Exclusion criteria were cardiac, pulmonary or vascular shunts; COPD; asthma; history of lung surgery (lobectomy or simple wedge resection); body mass index (BMI) ≥ 30 kg/㎡; and history of smoking.

All patients received a standard monitoring: electrocardiogram (ECG), saturation of pulse oximetry (SpO₂) and invasive blood pressure (IBP). Heart rate (HR) and IBP were recorded before anesthesia as the baseline. Anesthesia was induced with propofol (1.5–2.5 mg/kg), fentanyl (2–4 µg/kg), and rocuronium (0.6 mg/kg). Patients’ were ventilated with volume control ventilation (VCV), with a tidal volume (TV) of 6–10 ml/kg and an aspiration ratio (I:E) of 1:2, fraction of inspired oxygen (FiO₂) being 60% (2 L/min). The P_ETCO₂ values were kept as many as possible whin a range between 35 and 45 mmHg. However, P_ETCO₂ was also allowed to rise to 50 mmHg. P_ETCO₂ was measured by side stream spirometry (Mindray, BeneView T6, Shenzhen, China), while P_TCCO₂ was measured by the use of the TCM-4 monitor (Radiometer, Copenhagen, Denmark). Before placements, the electrode was cleaned and mounted with a new membrane. The calibration was done by a trained author (Shijiang Liu) according to the manufacturer's recommendations. The electrode was then placed on the patient’s chest of the non-operated side, which was swabbed with alcohol so as to facilitate the adhesion of the disk to the skin, with the electrode working temperature set at 44℃. The radial artery was cannulated on the non-operated side arm for ABG sampling. P_aCO₂ was determined with a blood gas/electrolyte analyzer (GEM premier 3000, Instrumentation Laboratory CO. 180 Hartwell Road Bedford, MA 01730–2443 USA). Before ABG sampling was performed, patients’ IBP, HR and TV were maintained constants for at least 5 minutes to assure a stable read of P_aCO₂. Meanwhile, P_TCCO₂ and P_ETCO₂ were recorded along with ABG sampling.

Anesthesia was maintained with propofol, sevoflurane and remifentanil to keep the variation of IBP and HR within a range of ± 20% of the baseline values. Patients who needed a vasoconstrictor to keep hemodynamics stable, or whose IBP drop was more than 20% of baseline value were excluded. The data before hypotension occurred could still be used for analysis. A communication with surgeons during surgery was carefully kept, as long as possible to maintain the integrity of the peritoneum. Once the peritoneum was ruptured, that patient would be excluded, but the data before peritoneal rupture was still available. The patients’ temperature was continuously monitored and maintained ≥ 36℃, meanwhile the room temperature was set at 23℃ − 25℃. The retroperitoneal CO₂ pressure stayed at 12–15 mmHg during the whole surgery. P_aCO₂, P_ETCO₂, and P_TCCO₂ values of each patient were measured at four time points: before CO₂ insufflation, 30 mins, 60 mins and 90 mins after CO₂ insufflation.

Statistic

GraphPad Prism 8 version (GraphPad Prism, La Jolla, California, USA) was applied for statistical analysis. Continuous variables were presented as mean ± SD. Bland-Altman analysis was used to compare P_TCCO₂ and P_ETCO₂ values to P_aCO₂. Pearson correlation coefficient and linear regression analysis were employed to establish the relationship. Paired t test were used to compare the difference of P_aCO₂ – P_ETCO₂ and P_aCO₂ – P_TCCO₂. The Fisher’s exact probability method and two-way contingency table were used to compare the number of differences ≤ 5 mmHg and ≤ 3 mmHg between P_aCO₂ – P_ETCO₂ and P_aCO₂ - P_TCCO₂. P < 0.05 was considered statistically significant.

66 patients were recruited in this study, whereas 6 patients were not interested before anesthesia and 10 patients were eliminated because phenylephrine was used during anesthesia induction. Finally, 50 patients (age 42.14 ± 14.24 year; body weight 65.5 ± 11.16kg; BMI 23.34 ± 2.99 kg/㎡) were involved, including 12 nephrectomy, 31 partial nephrectomy, 4 urethroplasty and 3 renal cyst excision. After the exclusion of the data with P_ETCO₂ < 35 mmHg and > 50 mmHg, 157 samples were obtained finally. The mean (SD) of P_aCO₂, P_ETCO₂ and P_TCCO₂ was 55.5 (7.2) mmHg, 42.3 (5.2) mmHg and 51.9 (84) mmHg, respectively. The above mean values of and correlation coefficients at each P_ETCO₂ levels were shown in Table 1. While the above mean values at each time point were displayed in Table 2. The absolute difference of P_aCO₂-P_ETCO₂ was 13.20 ± 4.43 mmHg (bias ± SD) and 4.35 ± 2.56 mmHg (bias ± SD) for P_aCO₂།P_TCCO₂ (P < 0.0001). The correlation coefficient (r) between P_aCO₂ and P_ETCO₂ was 0.79 (r² = 0.62, P < 0.0001) and the linear regression equation between P_aCO₂ and P_ETCO₂ was P_ETCO₂ = 0.60×P_aCO₂་9.10 (P < 0.0001, Figure. 1). The correlation coefficient between P_aCO₂ and P_TCCO₂ was 0.91 (r² = 0.83, P < 0.0001), and the linear regression equation between P_aCO₂ and P_TCCO₂ was P_TCCO₂ = 1.07×P_aCO₂།7.30, (P < 0.0001, Figure. 2).

Table 1

The correlation coefficient at Different P_ETCO₂ levels (Mean ± SD, n = 50)
	P_ETCO₂ (₃₅₋₄₀ mmHg)	r	P value	P_ETCO₂ (₄₀₋₄₅mmHg)	r	P value	P_ETCO₂ (₄₅₋₅₀ mmHg)	r	P value
P_aCO₂	50.61 ± 4.96			56.89 ± 4.49			63.11 ± 6.20
P_ETCO₂	37.73 ± 1.91	0.64	< 0.0001	43.12 ± 1.39	0.50	0.0003	50.03 ± 2.08	0.42	0.0098
P_TCCO₂	46.51 ± 5.94	0.88	< 0.0001	52.16 ± 5.32	0.75	< 0.0001	61.76 ± 6.31	0.85	< 0.0001
Correlation between end-tidal carbon dioxide partial pressure (P_ETCO₂) and transcutaneous carbon dioxide partial pressure (P_TCCO₂) compared to arterial carbon dioxide partial pressure (P_aCO₂) at 3 P_ETCO₂ levels.

Table 2

CO₂ Partial Pressure at Different Time Points (Mean ± SD, n = 50)
	Before pneumoperitoneum			After pneumoperitoneum
	Baseline (mmHg)	r	P value	30 min (mmHg)	r	P value	60 min (mmHg)	r	P value	90 min (mmHg)	r	P value
P_aCO₂	48.03 ± 3.53			57.48 ± 6.15			58.81 ± 5.91			56.15 ± 6.72
P_ETCO₂	36.92 ± 2.29	0.45	0.0047	43.65 ± 4.33	0.70	< 0.0001	43.62 ± 3.94	0.64	< 0.0001	44.79 ± 5.88	0.78	< 0.0001
P_TCCO₂	44.34 ± 4.26	0.81	< 0.0001	53.29 ± 7.80	0.90	< 0.0001	54.82 ± 7.04	0.85	< 0.0001	54.00 ± 9.10	0.91	< 0.0001
Correlation between end-tidal carbon dioxide partial pressure (P_ETCO₂) and transcutaneous carbon dioxide partial pressure (P_TCCO₂) compared to arterial carbon dioxide partial pressure (P_aCO₂) at 4 time points.

In all 157 samples, 1 of P_ETCO₂ values and 57 of P_TCCO₂ values were ≤ 3 mmHg from P_aCO₂ (P < 0.0001). Meanwhile 5 of P_ETCO₂ values and 101 of P_TCCO₂ values were ≤ 5 mmHg from P_aCO₂ (P < 0.0001). Bland-Altman analysis demonstrated that the 95% limits of agreement (LOA) of P_aCO₂ versus P_ETCO₂ was 4.53 to 21.88 mmHg (Figure. 3), while − 3.18 to 10.48 mmHg for P_aCO₂ versus P_TCCO₂ (Figure. 4).

The important findings of this study were that, P_TCCO₂ can estimate P_aCO₂ more accurately than P_ETCO₂ can do in patients under retroperitoneoscopic urologic surgery. Meanwhile, the correlation between P_TCCO₂ and P_aCO₂ was also better than that between P_ETCO₂ and P_aCO₂, even for the situation in which P_ETCO₂ was more than 45 mmHg.

Previous studies have found that P_TCCO₂ was an equivalent or even superior method for measuring P_aCO₂ in different patients [4–6], compared to P_ETCO₂ monitoring. However, the correlation of P_TCCO₂ and P_aCO₂ remained unknown in retroperitoneoscopic surgery. Our findings verified that P_TCCO₂ monitoring did possess a greater accuracy than P_ETCO₂ monitoring, and there were more values recorded which laid ≤ 3 mmHg or ≤ 5 mmHg from the real levels of P_aCO₂. Meanwhile, the Bland–Altman analysis indicated more precision with P_TCCO₂ monitoring than P_ETCO₂ (3.5 vs. 4.4 mmHg). Moreover, we also found that P_TCCO₂ and P_aCO₂ demonstrated excellent correlation than that of P_aCO₂ and P_ETCO₂ (0.91 vs. 0.79).

Operative position has a considerable influence on the accuracy of P_ETCO₂ monitoring. And retroperitoneoscopic urological surgery usually need a lateral position. Pansard JL et al [7] found kidney operation on lateral position could increase the difference between P_aCO₂ and P_ETCO₂, from 4.8 ± 3.9 mmHg on supine position up to 7.9 ± 3.5 mmHg on lateral position, also with an extension of time (8.8 ± 4.1 mmHg in 65 min, 8.9 ± 4.4 mmHg in 85 min). That is relevant to the change of V/Q on lateral position. To achieve lateral position during a kidney surgery even need a “kidney bridge”, formed by low head and proper foot positions (aggravate the imbalance of V/Q). Mahajan S et al [8] also found that P_ETCO₂ did not reliably predict P_aCO₂ in healthy patients scheduled for laparoscopic renal surgery in lateral position. For other types of surgery, Grenier B et al [9] compared several positions in neurosurgery and found the difference between P_aCO₂ and P_ETCO₂ in lateral position was larger than those in other positions (supine position, prone position and sitting position) because of a lower P_ETCO₂. The reason could be the increase of ventilation dead space in lateral position, which changed V/Q. In our study, P_TCCO₂ monitoring shows unique application value in lateral position surgery. There has no clear statement whether P_TCCO₂ monitoring can be affected by position, while tissue perfusion and electrode position can significantly affect the accuracy [10–12]. Therefore, we chose the front of chest in lateral position to ensure sufficient blood flow through the electrode.

The retroperitoneal space is different to the peritoneal cavity. In general, it does not normally exist, which is also wrapped in a large amount of fat. When the operation is needed, a retroperitoneal cavity is established by CO₂ insufflation, which extends upward to the neck and downward to the pelvic cavity. CO₂ can freely diffuse into this cavity, which may lead to subcutaneous emphysema and reduce the blood flow through the skin. During retroperitoneoscopic surgery, increased intraabdominal pressure and hypercarbia might be produced by CO₂ insufflation. Due to the increase of intraabdominal pressure, the insults of hemodynamics including increased afterload, preload and decreased cardiac output might be observed [13]. Clinically, hypercapnia mainly affects the cerebrovascular and cardiovascular. An increased P_aCO₂ causes cerebral vasodilation and increased intracranial pressure, although cerebral vessels have autoregulation function. Besides, acute hypercapnia may increase the release of catecholamines due to β-adrenergic stimulation, which might be detrimental in retroperitoneoscopic adrenalectomy, especially in pheochromocytoma surgery. The increase in the release of catecholamines exacerbates hemodynamic fluctuations. Because of the intermittence of ABG analysis, accurate predictions of P_aCO₂ level becomes significantly necessary clinically. In this present study, we’ve found an obviously better correlation between P_TCCO₂ and P_aCO₂, compared to that between P_ETCO₂ and P_aCO₂. On the other hand, the correlation coefficient between P_aCO₂ and P_TCCO₂ was 0.85 while only 0.42 between P_aCO₂ and P_ETCO₂ when P_ETCO₂ exceeds 45mmHg.

Previous studies have found that P_TCCO₂ can precisely estimate P_aCO₂, however many technical factors can still affect the accuracy of P_TCCO₂ monitoring, including monitor factors (penetration of air bubbles, incorrect electrode positions, damage of electrode membranes, and inaccurate calibration, etc.) and patients factors (skin blood perfusion, skin thickness, edema, dehydration, vascular active drug and anoxic acidosis. etc.) [14–16]. Heating electrodes can improve the reaction time, and increase local blood flow by the formation of local capillary arterialization, but it can also significantly lower the accuracy of the measurements. Nishiyama T et al [17] thought the electrodes should be heated to at least 43℃ to guarantee more accurate estimates of P_aCO₂ and P_aO₂. Sorensen LC et al [18] found that lower electrode temperature increases the system error of measured values in premature and neonates. The higher the temperature is, the greater the risk of skin burns will be. Hence, we chose 44℃ as the electrode temperature. No patients occurred with skin scald. Some of them had erythema, especially for females, which had faded away within 24h.

The present study has several limitations: First, we have not distinguished which patients developed subcutaneous emphysema, although no obvious subcutaneous emphysema was observed in the study. Second, the most accurate electrode position in the lateral decubitus position is still unknown. Third, there are not enough time points for each patient to be analyzed and a longer time span (somewhere after > 90 mins) is preferred to further observe the relationship between P_ETCO₂, P_TCCO₂ and P_aCO₂. Fourth, we only observed the correlation among P_ETCO₂, P_TCCO₂ and P_aCO₂ when P_ETCO₂ was within 35 mmHg – 50 mmHg which means we have no idea about the data out of the above range when patients undergoing retroperitoneoscopic urologic surgery.

Like BP, HR, and SpO₂, P_TCCO₂ monitoring can be used as another pair of “eyes” during perioperative monitoring for anesthesiologists. What's more important is that P_TCCO₂ monitoring is a real-time and noninvasive monitoring, without additional trauma to the patients.

In conclusion, P_TCCO₂ has been proved a more accurate method than P_ETCO₂ monitoring, on the aspect of estimating P_aCO₂ in patients undergoing retroperitoneoscopic urologic surgery. Although P_TCCO₂ might never replace the application of P_ETCO₂, it offers an effective approach for continuous P_aCO₂ monitoring. Also, it provides an early warning in patients who may suffer potential risk of hypercapnia.

Acknowledgements

We sincerely thank professor Changjun Yin (1964-2015) for his excellent contribution to the Department of Urology in our hospital. The authors acknowledge the people who contributed to this study and those who provided professional cares for those involved patients: Zengjun Wang, Pengchao Li, Pengfei Shao and Jie Li (Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu province, China). We are greatly indebted to Kai Zhang from the Pancreas Institute of Nanjing Medical University and the Pancreatic Center and Department of General Surgery at The First Affiliated Hospital of Nanjing Medical University for his guidance in statistical analysis.

Conflict of interest:

The authors declared that there is no conflict of interest regarding publication of this article.

Funding:

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Competing Interests:

The authors have no relevant financial or non-financial interests to disclose.

Author Contributions:

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Shijiang Liu, Yang Liu, Nan Li, Xian Wang and Shaokang Huang. The first draft of the manuscript was written by Shijiang Liu and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ethics approval:

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (Nanjing, Jiangsu province, China).

Consent to participate:

Informed consent was obtained from all individual participants included in the study.

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No competing interests reported.

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Transcutaneous carbon dioxide measurements in patients undergoing retroperitoneoscopic urologic surgery: A prospective observational study

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