Electrical impedance tomography-based evaluation of regional lung ventilation according to ventilation strategy during cardiopulmonary bypass in minimally invasive cardiac surgery: a prospective randomized controlled trial

Introduction

Recently, there has been increasing interest in minimally invasive cardiac surgery (MICS), which reduces bleeding, reoperation, postoperative pain, and length of stay in the intensive care unit (ICU) and promotes rapid recovery compared to conventional open cardiac surgery (1). In approximately 50–60% of MICS, extubation is performed in the operating room (OR) (2,3). In a previous study, MICS had a higher extubation rate than sternotomy, and even when extubation was performed in the OR, the frequency of postoperative complications, such as reintubation and pneumonia, was low (4). Cardiopulmonary bypass (CPB) is often used during MICS using a right thoracotomy approach, allowing both lungs to rest throughout the major procedure. However, CPB may contribute to pulmonary complications, which may increase the mortality and morbidity associated with cardiac surgery (5,6). It is particularly crucial to prevent postoperative pulmonary complications by promoting pulmonary ventilation and alveolar gas exchange during OR extubation after MICS.

To date, various strategies and interventions such as perioperative ventilation, restrictive blood transfusions, technical modifications of CPB, and administration of drugs, such as steroids, have been proposed and implemented to reduce the risk of lung injury. However, an appropriate ventilation strategy for the left lung during CPB remains unknown. Typically, during MICS, 2–3 ventilations before reinstalling controlled ventilation are performed at the end of CPB, and no ventilation is conducted while full CPB is applied until the aortic cross-clamp is released. Ventilation of both lungs begins upon weaning from CPB. However, most anesthesiologists do not ventilate the right lung and maintain it in a collapsed state to secure the surgical field of view during surgery. However, ventilation may be performed without affecting the view of the surgical site, even during CPB, because a double-lumen bronchial tube or bronchial blocker, depending on the anesthesiologists’ preference and level of familiarity, is used to isolate lung ventilation during MICS (7). Previous studies have shown that ventilation during CPB improves oxygenation, gas exchange, and immune response in patients who underwent cardiac surgery (8-12). However, no studies have quantified the effect of ventilation during CPB using objective devices, such as electrical impedance tomography (EIT). EIT is a noninvasive, radiation-free imaging technique that measures regional lung ventilation through changes in the electrical potential on the skin surface of the chest wall during the respiratory cycle (13). Identifying the occurrence of postoperative pulmonary ventilation dysfunction and differences in functional regional ventilation according to pulmonary ventilation strategy during CPB in MICS can help predict the risk of pulmonary complications and improve the prognosis of postoperative patients.

This study aimed to measure the distribution of pulmonary ventilation using EIT and check for any impairment of postoperative pulmonary ventilation according to the ventilation strategy during CPB in patients who underwent MICS with the right lung collapsed through a right minimal thoracotomy and underwent OR extubation. We hypothesized that left lung ventilation during CPB may have any respiratory benefit in MICS. We present this article in accordance with the CONSORT reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1877/rc).

Methods

Study design and patients

This study involved 60 patients after obtaining approval from the Institutional Review Board of Pusan National University Yangsan Hospital (IRB No. 05-2021-156). All the participants provided written informed consent. The clinical research was registered at ClinicalTrials.gov (ref. No. NCT04985513) and conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Adults aged ≥18 years who underwent minimally invasive surgery which requires one-lung ventilation (OLV) using a bronchial blocker were included in this study if there was no evidence of atelectasis in the preoperative chest X-ray (CXR) or chest computed tomography. The exclusion criteria were as follows: evidence of atelectasis, pneumonia, or lung disease that can reduce lung volume on chest radiography or chest computed tomography performed before surgery; moderately reduced lung function, emergent surgery, scheduled sternotomy; skin disease in the chest that inhibited EIT measurement; and transfer to the ICU while maintaining the endotracheal tube (Figure 1). Using randomization software (www.randomizer.org), the subjects were assigned to the non-ventilation (NV) group at an allocation ratio of 1:1, in which ventilation was stopped during CPB, or the ventilation (V) group, in which ventilation at a tidal volume (TV) of 5 mL/kg was applied during CPB. Sequentially numbered, opaque, and sealed envelopes that contain the assignments were opened, and the assignment was revealed to the investigator. All collected data has been anonymized and encrypted, then stored on a password-protected personal computer.

Figure 1 CONSORT flow diagram. Sixty patients who underwent minimally invasive cardiac surgery requiring OLV were enrolled in this study, and 30 patients were assigned to the V or NV group using a randomization program. Finally, 54 patients in the V and NV groups were analyzed. CPB, cardiopulmonary bypass; EIT, electrical impedance tomography; NV, non-ventilation; OLV, one-lung ventilation; OR, operating room; V, ventilation.

Anesthesia and monitoring

After the patient entered the OR, general anesthesia was induced using 1% propofol (1–2 mg/kg), rocuronium (0.8 mg/kg), and remifentanil while oxygenation under 5 L/min of oxygen for 3 minutes after applying a standard monitor. An experienced anesthesiologist inserted a single-lumen endotracheal tube containing an EZ blocker (AnaesthetIQ, Rotterdam, the Netherlands), a type of bronchial blocker, and confirmed proper placement using a fiberoptic bronchoscope. Anesthesia was maintained with inhalational anesthetics, such as sevoflurane and remifentanil, and the end-tidal sevoflurane was adjusted to maintain the bispectral index level at 40–60. Rocuronium, a neuromuscular blocker, was administered continuously at a rate of 9–12 µg/kg/min at our institution because the total dose of rocuronium by bolus injection was large due to the increase in blood volume during CPB. and discontinued after releasing the aortic cross-clamp. A neuromuscular monitoring device was attached to the medial wrist and ipsilateral thumb to continuously monitor the state of neuromuscular blockade before, during, and after surgery. If there were acceptable surgical results on transesophageal echocardiography, smooth weaning from CPB, stable hemodynamics with good cardiac function, no evidence of coagulopathy, and acceptable results on arterial blood gas analysis (ABGA), OR extubation was planned. To control postoperative pain, intravenous patient-controlled analgesia was performed in all patients using fentanyl at a concentration of 10–15 µg/mL, and demand bolus, background infusion rate, and lock-out time were set to 1 mL, 1 mL/h, and 15 min, respectively. During suturing of the skin, all patients were administered intravenous fentanyl 1 µg/kg. At the end of the surgery, the attending surgeon confirmed a lack of intrathoracic pleural effusion, bleeding, and atelectasis. Train-of-four monitoring was performed in all patients to confirm the residual neuromuscular blockade effect, and sugammadex was injected intravenously at 4 mg/kg if the response count to a stimulus was 0, and 2 mg/kg if the response count to a stimulus was 1 or more. The conditions for extubation of the endotracheal tube in the OR were as follows. Body temperature of 35.5 ℃ or higher; partial pressure of oxygen in arterial blood of 60 mmHg or higher on ABGA, and no acidosis (pH >7.25) at the end of surgery; hemodynamic stability; train-of-four ratio ≥90%; alert mentality of the patient; TV of 5 mL/kg or higher. After the endotracheal tube was removed, the patient was transferred to the ICU. Ten minutes after the patient entered the ICU, ABGA and EIT were performed under hemodynamic monitoring and oxygenation at 5 L/min via a nasal cannula.

Surgical procedure

After the patients were placed on their left side in a supine position at a 30° angle, the location of the EZ blocker was ensured by a fiberoptic bronchoscope. A 6-cm incision was made along the 4th intercostal space for mitral valve surgery and the 2nd intercostal space for aortic valve surgery. Peripheral cannulation through the right femoral artery and vein was performed with a semi-Seldinger technique. Cardioplegic arrest for myocardial protection was induced using antegrade cold blood cardioplegia following transthoracic aortic cross-clamping. All cardiac procedures were performed under mild hypothermia (29–34 ℃).

Ventilation strategy

After confirming the position of the bronchial blocker, the anesthesiologist performed bilateral lung ventilation by setting the TV to 8 mL/kg (predicted body weight), the positive end-expiratory pressure to 5 cmH₂O, and regulating the respiratory rate to maintain the partial pressure of end-tidal carbon dioxide in the range of 35–40 mmHg from the time of thoracotomy until CPB. The attending anesthesiologist performed OLV whenever requested by the attending surgeon. The TV was set at 5 mL/kg, and the positive end-expiratory pressure was set at 5 cmH₂O, and the respiratory rate was adjusted such that the partial pressure of end-tidal carbon dioxide was maintained within an acceptable range that did not cause acidosis. Hyperventilation was temporarily allowed when the pH was below 7.2. When the patient’s oxygen saturation was <90%, the attending anesthesiologist communicated with the attending surgeon to ensure ventilation of the patient, and manual ventilation of both lungs was performed immediately using 100% oxygen. Before closing the chest wall, adequate lung expansion was performed through alveolar recruitment with a peak inspiratory pressure of 30–40 cmH₂O lasting for approximately 5–10 seconds, and a positive end-expiratory pressure of 5 cmH₂O was applied after anesthesia induction. Positive end-expiratory pressure (PEEP) was not administered if the patient received auto-PEEP because of severe chronic obstructive pulmonary disease.

Different ventilation strategies were applied to each group during CPB. In the NV group, ventilation was stopped during CPB. In the V group, ventilation was performed using 20% oxygen, and a TV of 5 mL/kg without PEEP was set during the CPB (Figure 2).

Figure 2 Ventilation strategy. Different ventilation strategies were applied to each group during CPB. In the NV group, ventilation was stopped during CPB. In the V group, ventilation was performed using 20% oxygen, and a TV of 5 mL/kg was set during the CPB. FiO₂ before CPB was adjusted to maintain oxygen saturation above 90% rather than a single unified value. CPB, cardiopulmonary bypass; FiO₂, fraction of inspired oxygen; Lt., left; NV, non-ventilation; OLV, one-lung ventilation; PEEP, positive end-expiratory pressure; Rt., right; TV, tidal volume; V, ventilation.

Monitoring of EIT

After surgery, the endotracheal tube was extubated, and the patient was transferred to the ICU. Ten minutes after the patient entered the ICU, ABGA test and EIT monitoring were performed (Figure S1) using a PulmoVista 500^® Monitor (Drager Medical, Lübeck, Germany). In cooperation with the surgical team, the electrode belt for EIT monitoring was attached directly below the surgical site, and care was taken to avoid direct contact with the surgical site. The mid-position marker was located between the 8th and 9th electrodes and was positioned on the spine between the 4th and 6th intercostal spaces. After EIT monitoring was completed, the surgical team disinfected the surgical site again. The region of interest (ROI) is a user-defined region within the state image, and the EIT image can be divided into four ROIs and arranged horizontally, in quadrants, or in a user-defined manner. In this study, ROI 1, ROI 2, ROI 3, and ROI 4 were designated as the right anterior area of the lung, the left anterior area of the lung, the right posterior area of the lung, and the left posterior area of the lung, respectively (Figure S2). The global inhomogeneity (GI) index is a number that quantifies the distribution of TV. The ideal value is 0.5, and an increase in the GI index is known to be associated with lung injury. Differences in GI index and quadrants in the ROI were confirmed between the groups. The measured value of the collapsed right lung field was used as the reference value. The index value in the left lung, which was calculated by dividing the ROI of the left lung field by that of the right lung field as the reference value, was also compared between the two groups, as shown below:

Example: index value of left anterior areas of the lung = ROI of left anterior regions of the lung / ROI of right anterior regions of the lung; index of left posterior area of the lung = ROI of left posterior regions of the lung / ROI of right posterior regions of the lung.

Primary and secondary endpoints

The hypothesis of this study was that left lung ventilation during CPB may have any respiratory benefit in MICS. The primary endpoint was to confirm differences in the regional ventilation ratio (quadrants in the ROI) and GI index between the V and NV groups. The index value for each group was calculated by dividing the ROI of the left lung field by that of the right lung field, and the measured value of the collapsed right lung field was set as the reference value. The secondary endpoint was the difference in the incidence of postoperative pulmonary complications according to the pulmonary ventilation strategy during CPB in MICS. Postoperative pulmonary complications are defined as clinical symptoms such as respiratory infection, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonia that occur within 7 days after surgery, and can be diagnosed through CXR or computed tomography (14). Pneumonia was diagnosed when patchy, nodular, or mass-like opacities were seen on CXR, and atelectasis was diagnosed when platelike, horizontal lines in the area of atelectatic lung tissue, displacement of interlobar fissures, pulmonary opacification, or tracheal shift toward the affected side were seen on CXR. Low cardiac output syndrome is a clinical condition caused by a temporary decrease in systemic perfusion due to myocardial dysfunction, and it is diagnosed with signs and symptoms including tachycardia, hypotension, increased capillary refill time, decreased peripheral pulse, cold extremities, and decreased urine output (15). Vasoactive-inotropic score is the weighted sum of all administered inotropes and vasoconstrictors, and reflects cardiovascular pharmacological support. Vasoactive-inotropic score was calculated as dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 × epinephrine dose (µg/kg/min) + 100 × norepinephrine dose (µg/kg/min) + 10,000 × vasopressin dose (U/kg/min) + 10 × milrinone dose (µg/kg/min) (16).

Statistical analysis

Continuous variables were examined for normality using the Shapiro-Wilk test. Normally distributed variables were compared using the Student’s t-test, whereas non-normally distributed variables were compared using the Kruskal-Wallis test. Numerical results were expressed as mean ± standard deviation or median (interquartile range), as appropriate. Categorical variables were examined using two-tailed Fisher’s exact test or the Chi-squared test. Statistical significance was defined as a P value <0.05. All statistical analyses were performed using IBM SPSS Statistics (version 25.0; IBM Corp., Armonk, NY, USA) or R version 3.6.2.

Sample size considerations

The sample size was calculated using the G*Power 3.1.9.7 program. There was no study with a similar design, and the effect size calculated based on reference (17) was very large, around 3. Therefore, the effect size on left lung ventilation was thought to be large and the effect size was calculated as 0.8. When the significance level was 0.05, the power was 0.8, and the effect size was 0.8; the number of samples required was 26 for each group, a total of 52. Therefore, considering a 15% dropout, the number of participants was set to 60.

Results

Sixty patients who underwent MICS surgery requiring OLV were enrolled in this study from August 2, 2021, to February 9, 2022, and 30 patients were assigned to the V or NV group using a randomization program. Three patients in the V group were excluded because of failed OR extubation (N=1) and unavailable ventilation during CPB due to an unfavorable surgical field (N=2). Three patients in the NV group were excluded because of failed OR extubation (N=2) or failed fastening of the EIT belt because the patient’s chest circumference was too large (N=1). Finally, 54 patients in the V and NV groups were analyzed (Figure 1).

Baseline characteristics of patients

Table 1 shows the baseline characteristics of the two groups. There were no statistically significant differences in age (62.5±9.9 years in the V group vs. 57.7±14.7 years in the NV group) or gender distribution between the two groups. No significant differences were found between the groups except for atrial fibrillation. The prevalence of preoperative atrial fibrillation was higher in the V group (25.9 % vs. 0%, P=0.005).

Regional ventilation ratio and GI index (Table 2)

No significant difference was observed in global ventilation. When divided into four compartments and compared, a significant difference was noted in the right posterior area (V group 18.8%±4.2% vs. NV group 22.3%±7.3%, P=0.03). The ventilation ratio in the left posterior area tended to be higher in the V group than in the NV group (22.7%±5.2% vs. 20.1%±4.7%, P=0.054). The GI index was higher in the NV group than in the V group (0.5±0.1 vs. 0.6±0.2, P=0.02). That is, the ventilation inhomogeneity was significantly higher in the NV group. Additionally, when comparing the ventilation amount on the left side using the right side as a reference value, the index of a left posterior area in the V group was higher (1.3±0.4 vs. 1.0±0.3, P=0.003).

Early complication within 1 week between the two groups

No difference was found in the ABGA performed immediately after admission to the ICU between the two groups (Table 3). No significant differences were noted in early complications within 1 week after surgery. Postoperative pulmonary complications, such as reintubation and pneumonia, did not occur in either group.

Discussion

This study showed significant differences in GI and left posterior index values according to the ventilation strategy in the left lung during CPB in patients undergoing MICS. In the V group, the ventilation inhomogeneity of the entire lung was reduced, and ventilation in the left posterior area increased. However, no difference was observed in clinical outcomes, including ABGA and postoperative respiratory complications. Since no respiratory complications occurred in either group, the clinical effects of ventilation during CPB could not be confirmed.

The use of MICS has recently increased owing to rapid recovery and low incidence of complications (1). Although OR extubation is often performed, concerns persist regarding bleeding, hemodynamic instability, atelectasis, and reintubation. A previous study has shown that our institution performs OR extubation in approximately 50% of patients after MICS (3); however, our reintubation rate was as low as 0%. Further, in other institutions, the reintubation rate was low at approximately 4–5% (18). Pulmonary dysfunction after MICS can be influenced by several factors, among which atelectasis is considered a major cause of gas exchange impairment after CPB (19-21). Notably, it has been reported that atelectasis occurs in 64% of patients after cardiac surgery (22). During CPB, mechanical movement during pulmonary ventilation can interfere with surgery; hence, most cardiac surgeries implement ventilation cessation during CPB. Stopping mechanical ventilation can lead to local atelectasis, maintenance of bronchial secretions, increased venous admixtures, pressure-induced pulmonary edema, reduced compliance, and increased infection rates (23-25). Even if normal ventilation is performed after CPB, collapse injuries (atelectrauma) may occur because of the shearing force resulting from repeated collapses and the expansion of areas affected by atelectasis (26). This atelectasis can result in not only ventilation failure and ventilation/perfusion imbalance but also the development of postoperative pneumonia and a poor prognosis (27). Therefore, several studies have attempted to investigate whether ventilation during CPB can improve oxygenation and prevent the deterioration of pulmonary function after cardiac surgery (17,28,29).

Traditionally, a right-sided thoracotomy is preferred for MICS. From the beginning of surgery until access to the surgical site or at the end of surgery, the right lung collapsed, and ventilation was conducted solely on the left lung through the OLV to check for bleeding at the surgical site. Consequently, OLV may be required even after discontinuation of CPB, which could further increase the risk of atelectasis in the lungs on the surgical side. Ventilation of the left lung during surgery and TV can influence the development of postoperative atelectasis and may lead to functional ventilation disorders. Previous studies have reported that ventilation during CPB reduced postoperative oxygenation and lung mechanics (17,28-30). However, these studies have only analyzed arterial blood gas and clinical complications and did not objectively measure the degree of pulmonary ventilation.

EIT is a non-invasive, radiation-free imaging technique that measures regional lung ventilation through changes in the electrical potential on the skin surface of the chest wall during ventilation (31). According to Zhao et al., the GI index is a reliable measure of ventilation heterogeneity in patients with acute respiratory distress syndrome. Therefore, this is a valuable index for guiding ventilation therapy (32). In this study, ventilation during CPB showed better left posterior ventilation and ventilation homogeneity, but did not result in a difference in respiratory complications. However, left lung ventilation during CPB in MICS makes the surgical field invisible. Left lung ventilation pushes the mediastinum forward, which may eventually reduce the space between the sternum and the surgical area. Therefore, implementing left-lung ventilation can reduce the exposure of the surgical field during MICS via right anterior thoracotomy. In this study, two of three patients in group V were excluded owing to poor visibility during surgery. Therefore, because there is no respiratory benefit, ventilation during CPB in short surgeries with a CPB time of <90 min may be unnecessary.

This study had several limitations. First, left lung ventilation was performed using a TV of 5 mL/kg without PEEP during CPB, and thus, the alveolar opening may be limited. Second, our results are specific to MICS and cannot be generalized to open thoracotomies. It is challenging to apply the data obtained in this study to all cardiac surgeries. Because the EIT was measured immediately after the patient was admitted to the ICU, it is possible that deep spontaneous breathing was not restored because of pain and the patient’s inability to cooperate. We only assessed the early postoperative outcomes according to ventilation during CPB; therefore, the effect of unilateral lung ventilation on the lung contralateral to surgery during CPB has not been evaluated in the hours to days after surgery. If additional research is to be conducted, it is necessary to evaluate clinical effectiveness by performing EIT, ABGA, and pulmonary function tests in periods other than immediately after surgery. Since the respiratory disease morbidity rate in this study’s subjects was low (~10%), the risk of postoperative pulmonary complications may also have been low. To identify clinically meaningful differences in ventilation-related complications during CPB, studies should focus on either large low-risk populations or high-risk patients with factors such as low left ventricular ejection fraction, preoperative bronchodilator use, high EuroSCORE II, left ventricular assist device implantation, major thoracic aortic surgery, or prolonged CPB duration (33). Nevertheless, this study may have answered the question of whether ventilating the lung on the contralateral side of the surgery during CPB in MICS would help improve lung function after surgery. It was concluded that ventilation during CPB is not necessary in MICS with a CPB duration of <90 min. Additionally, the plateau pressure of the airway was not recorded after induction of anesthesia, during OLV before starting CPB, and after weaning from CPB. Therefore, the evaluation of lung mechanics, such as static lung compliance, could not be performed. Despite these limitations, this study is the first to evaluate ventilatory function using EIT in spontaneous breathing immediately after OR extubation by applying different ventilation strategies during CPB in patients with MICS. Further research is warranted to investigate the impact of postoperative ventilation according to the ventilation strategy during CPB in cardiac surgery.

Conclusions

Our study found that left lung ventilation during CPB improved the ventilation homogeneity and left posterior lung ventilation. However, this did not lead to differences in early complications, including respiratory complications. Therefore, the necessity of left lung ventilation during CPB in short surgeries with a CPB time of <90 min is unclear.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1877/rc

Trial Protocol: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1877/tp

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1877/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1877/prf

Funding: This study was supported by a 2025 research grant from Pusan National University Yangsan Hospital.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1877/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of Pusan National University Yangsan Hospital (IRB No. 05-2021-156), and informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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