Invasive CO₂ monitoring with arterial line compared to end tidal CO₂ during peroral endoscopic myotomy^[*]

Introduction

Achalasia is a motor disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter, as a consequence of the loss of myenteric neurons. There are multiple options available for its treatment, including medications, pneumatic balloon dilation, and surgical myotomy [1] [2]. POEM is an endoscopic technique that evolved from the concept of natural orifice transluminal endoscopic surgery. The procedure involves the creation of a submucosal tunnel and then myotomy of the muscular fibers of the distal esophagus, including the lower esophageal sphincter. First described in humans more than a decade ago, the reported safety and clinical efficacy of this treatment modality in all types of achalasia, as well as in other spastic disorders of the esophagus, has been well demonstrated [3] [4].

Carbon dioxide (CO₂) insufflation is a crucial component of third space endoscopy, and permits work in the submucosal space with less risk of barotrauma because it is reabsorbed faster than air [3] [5]. Controlled or minimized CO₂ insufflation during the creation of the submucosal tunneling, as well as during the myotomy, can still be associated with complications [6]. The recognition and treatment of the physiological changes that occur as a consequence of CO₂ is of utmost importance to improve patient safety. End tidal CO₂ (ETCO₂) offers an acceptable estimate of alveolar CO₂ measured as arterial CO₂ (PaCO2) [7], and is recommended as a surrogate for PaCO₂ in most patients, although its reliability can be compromised in patient with pulmonary diseases [7] [8].

PaCO₂ provides the most accurate evaluation of alveolar CO₂ but requires the presence of an arterial line. Interestingly, no study has evaluated whether there are any differences between invasive and noninvasive CO₂ monitoring during POEM. The aim of our study was to elucidate if the use of an arterial line with direct measurement of PaCO₂ was of any benefit, when compared to only ETCO₂.

Patients and methods

Patient population

A prospective comparative study was performed in our institution. Information on all patients 18 years or older who underwent POEM for the treatment of achalasia and were able to provide consent was included in a prospectively collected database. Information on patients with known pulmonary disease or advanced cardiovascular disease was excluded. A total of 71 patients were included in the study. In the group in which PaCO₂ plus ETCO2 was measured, also known as invasive group, included 32 patients, an arterial line was placed prior to starting the POEM and the PaCO₂ was checked on average every 28 minutes. The group in which only ETCO₂ was measured, also known as the noninvasive group, included 39 matched patients. ETCO₂ was recorded every 12 minutes on average in both groups.

Periprocedure details

All the patients at our institution require a thorough evaluation before a diagnosis of achalasia is made, which includes a history and physical focusing on the Eckardt score, esophagogastroduodenoscopy, high-resolution manometry and endoluminal impedance measurement. Absolute contraindications for POEM are severe coagulopathy unable to be reversed as well as end-stage cirrhosis with sequelae of portal hypertension such as esophageal or gastric varices.

After the decision has been made for POEM, patients are placed on a full liquid diet for 2 days prior to the procedure, and then nil per os (NPO) for at least 8 hours. Preprocedurally patients are given a high-dose proton pump inhibitor (PPI), scopolamine patch and ondansetron to prevent nausea as well as prophylactic antibiotics, usually a quinolone.

The procedure is performed under general anesthesia with endotracheal intubation, paralytics are usually administered throughout the procedure, and pressure-controlled ventilation is favored over volume-controlled ventilation. In the pediatric population, the available evidence about the best anesthetic practices for POEM is scarce, and usually management is driven by the available data from adult patients [9]. The patient is placed in the supine position, and the endoscopist performs the procedure at the head of the bed, which allows for continuous visualization of the patient’s abdomen to monitor for the development of capnoperitoneum [10]. A high-definition gastroscope is required, with 4-mm transparent cap attached to the distal end. Several endoscopic knives and an electrosurgical generator are used for dissection; however, a hybrid knife (ERBE, Marietta, Georgia, United States) is preferred to allow simultaneous injection and dissection. A posterior approach is usually chosen for dissection and myotomy, and submucosal injection is performed using a solution consisting of normal saline and methylene blue. A coag gasper (Olympus, Center Valley, Pennsylvania, United States) is used to prevent or treat bleeding. CO₂ is used for insufflation with an insufflator with adjustable output flow rate ranging from ultralow to high (ERBE). Medium flow is used before tunneling and then is switched to low during submucosal dissection and myotomy; if there is persistent elevation of CO₂ on ETCO₂, the flow is switched to ultralow. There is also continuous communication with the anesthesia team and the respiratory rate is also increased to decrease the CO₂. When there is persistent CO₂ elevation along with elevated peak pressure despite the aforementioned measures, the neck, chest and abdomen are examined to look for signs of CO₂ extravasation at those sites. When there is significant abdominal distention, suctioning of the stomach is performed using the endoscope, and then percutaneous needle decompression of pneumoperitoneum is carried out with a 14G needle to decrease the level of CO₂ on ETCO₂. If there is persistent elevation of CO₂, the procedure is temporarily stopped until the CO₂ on ETCO₂ drops below 40 mm Hg. After the myotomy is performed, the tunnel can be lavaged with diluted gentamycin on a case-by-case basis. Finally, the tunnel is closed using endoscopic clips or endoscopic suturing.

Patients are extubated post procedure and recover in the postprocedure area of the endoscopy unit. Most of our patients are admitted to the hospital 1 night for observation and kept NPO until a gastrografin esophagram is performed the next day to rule out contrast extravasation. After a negative study, a clear liquid diet is started and if the diet is tolerated, patients are discharged home on antibiotics to complete 5 days of treatment. High-dose PPI and antiemetics are continued on discharge. Patients continue a clear liquid diet for 3 days, and then transition to a full liquid diet for another 3 days and then a soft diet, which is advanced as tolerated.

Statistical analysis

Data were captured in a registry (NCT05051358) deemed exempt by WCG IRB (February 17, 2021).

Information on demographics, procedural details, post-procedure outcomes, and adverse events (AEs) was collected and compared. Results are reported as mean ± standard deviation (SD) or median (range) for quantitative variables and percentages for categorical variables. The difference in procedure time, anesthesia time as well as AEs were reported in both groups. Significant associations were defined as P < 0.05.

We calculated Pearson correlation coefficient (PCC) and Spearman’s Rho to calculate the correlation between PaCO₂ and ETCO₂. PaCO₂ plus ETCO₂ were measured in 32 patients (invasive group) and ETCO₂ only in 39 matched patients (noninvasive group).

Two-sided P < 0.05 were considered statistically significant. All descriptive and statistical analyses were conducted using MedCalc V18.9 (MedCalc Software, Ostend, Belgium).

Results

Both groups had similar demographics and there were no significant differences in age, length of myotomy, subtype of achalasia or severe tortuosity when comparing the groups ([Table 1]). The average procedure time (scope in and out) was increased 17.7 minutes (P = 0.04) in the invasive monitoring group ([Table 2]). Anesthesia duration was increased 46.3 minutes in addition to endoscopy time in the invasive monitoring group (P ≤ 0.00001). Within the PaCO₂ group, the average difference between PaCO₂ and ETCO₂ was 3.39 mm Hg (Median 3, SD 3.5), within the 2– to 5-mm Hg range ([Fig. 1]). The Frequency of ETCO₂ monitoring in the two groups was not significantly different (P = 0.74). PaCO₂ and ETCO₂ were strongly correlated in patients undergoing POEM, PCC R value: 0.8787 P ≤ 0.00001, Spearman’s Rho R value: 0.8775, P ≤  0.00001.

Table 1 Demographics of both groups, PaCO₂ plus ETCO₂ and ETCO₂ only.

Groups	PaCO2 + ETCO2 group			ETCO2 only group
Cases	N = 32			N = 39
Males/females	14/18 (44 %/56 %)			15/24 (38 %/62 %)
Age (standard deviation)	54.41 mean (16.04)			58.6 mean (19.44)
Esophageal myotomy	13 cm mean			13 cm mean
Gastric myotomy	3 cm mean			3 cm mean
Achalasia subtypes	I n = 10 (31 %)	II n = 17 (53 %)	III n = 5 (16 %)	I n = 12 (31 %)	II n = 21 (54 %)	III n = 6 (15 %)
Severe tortuosity/sigmoid esophagus	3 %			5 %

PaCO₂, partial pressure of CO₂ , ETCO₂, end tidal CO₂.

Table 2 Comparison between both groups, PaCO₂ plus ETCO₂ and ETCO₂ only.

Groups	PaCO2 + ETCO2 group			ETCO2 only group			P value
Cases	N = 32			N = 39
Males/females	14/18			15/24
	Average	Median (range)	SD	Average	Median (range)	SD
Procedure time in minutes (scope in and out)	96.7	80 (50 to 291)	50.7	79	70 (22–172)	33.2	0.04
Age	54.41	58 (22–88)	16.04	58.6	63 (18–94)	19.44	0.33
pH	7.37	7.38 (7.22 to 7.5)	0.064	N/A	N/A	N/A
PaCO2 (mm Hg)	41.23	41 (26 to 64)	7.3	N/A	N/A	N/A
PaCO2 frequency in minutes	Every 28	Every 27 (14.5 to 56)	7.8	N/A	N/A	N/A
ETCO2 (mm Hg)	37.8	38 (26 to 60)	5.6	36.7	37 (27 to 48)	4.21	0.27
ETCO2 frequency in minutes	Every 12.3	Every 11.6 (4.9 to 29.2)	4.9	Every 11.9	Every 12.8 (3 to 14.5)	3.6	0.74
Adverse event	13 % (3 hand hematoma,1 nerve injury)			3 % (1 pneumothorax[1])			0.24

PaCO₂, partial pressure of CO₂ , ETCO₂, end tidal CO₂; SD, standard deviation; N/A, not applicable.

¹ Inadvertent use of air instead of CO₂ during the procedure.

Fig. 1 Correlation between PaCO₂ and ETCO₂.

There were no differences between the groups in AEs (13 % vs 3 % P = 0.24). AEs included three hematomas and one nerve injury related to arterial line placement in the invasive group and one pneumothorax due to inadvertent air insufflation in the noninvasive group. The episode of pneumothorax in the noninvasive group was caused by inadvertent use of air instead of CO₂ insufflation, and required stopping the procedure as well as chest tube placement. After the pneumothorax resolved the patient decided not to pursue another procedure.

The three hematomas in the invasive group were managed conservatively while the patient with nerve injury is undergoing ambulatory physiotherapy.

Discussion

Appropriate distention is required for good visibility during endoscopy. Initially air was being used for insufflation during endoscopy and in the 1970 s, it was discovered that use of electrosurgical instruments during air insufflation could lead to a fatal explosion in the bowels and barotrauma, [11]. CO₂ happens to be less expensive and more rapidly absorbed than regular air, because CO₂ is absorbed 160 times faster than nitrogen and 12 times faster than oxygen, the two main components of air. After being absorbed, the CO₂ is transported by the blood to the lungs and then exhaled [12].

POEM involves the creation of a tunnel across the submucosal space with frequent exposure of the mediastinum. The most common AEs associated with POEM are related to excess insufflation, including pneumomediastinum, pneumothorax, pneumoperitoneum, and subcutaneous emphysema because endoscopically insufflated gas may be inadvertently absorbed into surrounding tissues, compromising cardiorespiratory function. According to prior studies, insufflation-related AEs are quite variable in incidence, ranging from 7.5 % to 55.5 % [13] [14] [15] [16] [17].

Initial studies of POEM showed that use of CO₂ was associated with less risk of insufflation-related complications when compared to air, and although its use did not completely eliminate the risk, it was decreased substantially [18] [19]. The use of general anesthesia also facilitates achievement of positive intrathoracic pressure and decreases risk of mediastinal emphysema [20].

CO₂ plays various roles in the human body, including regulation of blood pH, respiratory drive, and affinity of hemoglobin for oxygen; therefore, CO₂ levels should be closely monitored to maintain them under 45 mm Hg [13] [21]. It is estimated that partial pressure of CO₂ (PaCO₂) is 2 to 5 mm Hg higher than ETCO₂ [22] [23], and the recommended level of ETCO₂ during POEM is approximately 40 mm Hg. Another parameter to consider is the peak inspiratory pressure or P_max; elevated peak pressure ( > 38 cm H₂0 or 20 % above the baseline) along with abdominal distention could represent increased abdominal pressure, and the need for percutaneous needle decompression of pneumoperitoneum [21] [24].

Previous studies have demonstrated the adequacy of ETCO₂ to evaluate hypercapnia and monitor ventilation during anesthesia because it is continuous and noninvasive [7] [8] [22] [25] [26].

This prospective comparative study confirmed that, among patients undergoing POEM, ETCO₂ correlates strongly with PaCO₂ with an average difference that is within the expected 2- to 5-mm Hg range as reported in studies in non-POEM patients [22] [23]. The gradient between ETCO₂ and PaCO₂ is directly proportional to the degree of physiologic dead space [27] [28] [29]. Although the typical alveolar CO₂ concentration is slightly greater than PaCO₂, ETCO₂ is normally 2 to 5 mm Hg lower than PaCO₂ due to mixing of CO₂-containing alveolar gas with exhaled gas devoid of CO₂ from the anatomical dead space. As a result, ETCO₂ levels are maintained in a normal physiologic range (30–40 mm Hg), corresponding to a PaCO₂ range of 35 to 45 [21] [22] [23]. Because the observed average difference in ETCO₂ and PaCO₂ in our study was within the 2– to 5-mm Hg range, ETCO₂ can be used as a noninvasive surrogate measure for PaCO₂ in patients undergoing POEM. In patients with concurrent lung disease, the reliability of ETCO₂ can be compromised because the 2- to 5-mm Hg gradient can increase with any increase in the dead space volume; indeed, the addition of alveolar dead space further dilutes ETCO₂ relative to PaCO₂. In such patients, endoscopists should exercise caution because the same ETCO₂ values may reflect greater PaCO₂ values, and thus, increased risk of hypercapnia-related complications [7] [8].

Although it is recognized that POEM poses unique anesthesia-related challenges, standardized management has yet to be established and the necessity for arterial line placement has not previously been investigated. In our study, there was no significant difference in AEs between the invasive and noninvasive groups, suggesting that using ETCO₂ as a safe surrogate measure for PaCO₂ allows for prompt recognition and response to emergent hypercapnia-related complications. While there was an instance of pneumothorax in the noninvasive group due to use of air for insufflation instead of CO₂, it was inadvertent and not due to using ETCO₂ as a surrogate measure for PaCO₂. However, compared to POEM procedures performed in the invasive group, those performed in the noninvasive group had a significantly shorter mean procedure time and anesthesia duration. Longer procedure times and anesthesia durations among the invasive group due to the placement of an arterial line may increase the risk of complications. In our study, the widespread placement of arterial line was associated with an increased incidence of hematoma and nerve injuries.

A retrospective case series review by Loser et al demonstrated that insufflation-related cardiorespiratory responses are likely inevitable during POEM. The cardiorespiratory response tends to include an increased peak inspiratory pressure, ETCO₂ levels, mean arterial pressures, and heart rate [24]. The goal of periprocedural monitoring is to identify abnormalities at an early stage to prevent or mitigate harm to the patient [7]. Previous studies have reported the safety of ETCO₂ during POEM [13] [21] [24]. Our study has several strengths, including being the first to compare invasive versus noninvasive CO₂ monitoring in patients undergoing POEM, demonstrating that ETCO₂ correlates strongly with PaCO₂ and should be used as a surrogate of PaCO₂ in patients undergoing POEM, and universal PaCO₂ monitoring contributes to increased duration of anesthesia, as well as total procedure and turnover time.

Conclusions

In conclusion, POEM is a relatively new procedure, continuously evolving. It has unique perioperative aspects that need to be understood by the team performing the procedure, which includes the endoscopist, the anesthesiologist, anesthetist, perioperative nurses and endoscopy technician.

One of the limitations of our study is that it was not randomized. However, it demonstrates the viability of ETCO₂ as a surrogate measure for PaCO₂, allowing recognition of CO₂-related complications without the need for arterial line placement during the POEM procedure. Invasive CO₂ monitoring with an arterial line should be performed in patients with major cardiopulmonary comorbidities on a case-by-case basis.

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