DOI: https://doi.org/10.21203/rs.3.rs-2195462/v1
The optimal ventilation mode for patients with obesity undergoing laparoscopic surgery remains unclear. In this prospective randomized controlled study, the effects of two ventilation modes, pressure-controlled ventilation (PCV) and pressure-controlled ventilation - volume guaranteed (PCV-VG), on perioperative oxygenation and respiratory mechanics were compared in patients undergoing laparoscopic bariatric surgey.
A total of 110 subjects were randomly divided into PCV-VG group (n = 56) or PCV group (n = 54). The perioperative pulmonary mechanics and arterial blood gas results were compared between the two groups. Postoperative extubation time, the incidences of postoperative pulmonary complications (PPCs) and abnormal radiographic changes (ARCs) were also recorded.
During intraoperative pneumoperitoneum, the respiratory dynamic compliance (Cdyn) was significantly lower in PCV-VG group than that in PCV group. There were no significant differences in perioperative oxygenation index and respiratory peak pressure (Ppeak) between the two groups. Eighty-six subjects (78.2%) had ARCs on the 1st day after surgery, only ten subjects (9.1%) developed PPCs. There was no significant difference in extubation time, ARCs or PPCs between the two groups. After adjustment, anesthesia duration and oxygenation index before anesthesia induction were significantly associated with extubation time. Anesthesia duration of more than 2 hours was a risk factor for postoperative radiographic abnormalities.
Compared with PCV-VG mode, PCV mode provides better pulmonary compliance during intraoperative pneumoperitoneum. Further large-sample studies are needed to determine the optimal ventilation mode in subjects with obesity undergoing laparoscopic surgery.
With the changes in Chinese dietary structure and lifestyle, obesity has become a growing health concern in China over the last two decades [1]. Compared to normal-weight subjects, obese subjects present increased weight of chest wall, contributing to the reduction of total respiratory compliance and functional residual capacity [2]. Perioperative pneumoperitoneum further leads to severe pulmonary peak pressure increase and respiratory compliance reduction, by pushing paralyzed diaphragm cephalad, in obese subjects undergoing laparoscopic surgery [3]. Therefore, obese subjects experience more postoperative pulmonary complications (PPCs), including atelectasis, pneumonia, tracheal reintubation, respiratory failure and death [4]. Specific perioperative ventilation strategies are required for the obese population.
Many clinical researchers have reported inconsistent perioperative ventilation approaches for obese patients, for example, various tidal volume (VT), ventilation modes, PEEP, recruitment maneuvers, or multiple combinations thereof [5]. In terms of ventilation modes, volume-controlled ventilation (VCV), pressure-controlled ventilation (PCV), and pressure-controlled ventilation - volume guaranteed (PCV-VG) are regular modes used in clinical practice. Compared with VCV mode, PCV mode delivers the same VT at lower inspiratory peak pressures (Ppeak) for the obese population. However, PCV mode supplies varying VT with changing lung compliance (e.g. laparoscopic surgery), increasing risks of hypoventilation or hyperventilation. PCV-VG, integrating the advantages of both VCV and PCV, autoregulatively gives the preset target VT with the lowest airway pressure. In theory, PCV-VG mode may be better than PCV mode with higher respiratory compliance and perioperative oxygenation. There is no consensus regarding the optimal ventilation mode between PCV and PCV-VG for the obese population.
In the current study, we compared the effects of the two ventilation modes (PCV vs. PCV-VG) on perioperative oxygenation, respiratory mechanics and PPCs in subjects undergoing elective bariatric surgery, aiming to identify an optimal ventilation mode for obese subjects undergoing laparoscopic surgery.
We conducted a prospective randomized controlled study in obese subjects undergoing elective bariatric surgery in Huashan Hospital, Fudan University between January 2018 and March 2020. Inclusion criteria included adult (age between 18 year to 65 year), body mass index (BMI) more than 30 kg/m2, American society of anesthesiologists (ASA) physical status classification 1–2. Exclusion criteria were age less than 18 year or more than 65 year, BMI less than 30 kg/m2, ASA classification 3–4, surgical history of lung lobe resection, respiratory diseases (pneumonia, pneumatoceles, restrictive or obstructive respiratory dysfunction), cardiac diseases (ventricular arrhythmia, congestive heart failure, valvular stenosis or insufficiency), severe liver, kidney or cerebral dysfunction, or refusal to give written informed consent. The subjects were randomly enrolled in a 1:1 ratio to one of the two groups (PCV or PCV-VG mode) based on computer-generated random numbers.
All patients were given general anesthesia. The combinations of propofol (1–2 mg/kg), fentanyl (4–6 µg/kg) and rocuronium (0.9mg/kg) were administered for intravenous induction based on ideal body weight (IBW). IBW(kg) for males = 50 + 0.91 × (centimeters of height − 152.4); IBW for females = 45.5 + 0.91 × (centimeters of height-152.4) [6]. 2–3% sevoflurane were given to maintain anesthetic depth combined with fentanyl and rocuronium. Pneumoperitoneum with 12–14 mmHg and reverse Trendelenburg position (50–60 degrees) were utilized in this surgical procedure named laparoscopic sleeve gastroplasty. After surgery, all subjects were immediately transferred to the postoperative care unit (PACU). Neostigmine (0.05-0.07mg/kg) and neuromuscular monitoring (trains of four, TOF) were regularly used to prevent the residual neuromuscular blockade. The subjects’ tracheal tube was not removed until their spontaneous VT was greater than 6ml/kg and the TOF ratio was greater than 90%.
Individuals’ demographics and characteristics (e.g. age, gender, height, and weight) were collected by one research coordinator. The surgical and anesthetic characteristics were also obtained including surgical duration, anesthesia duration, and postoperative extubating time. The subjects were randomly ventilated with 8 ml/kg (IBW) plus PEEP 5 cmH2O in PCV or PCV-VG mode. Inspiration and expiration ratio (I/E) was set as 1:2. The gas flow rate was 2ml/min. Recruitment maneuvers, keeping airway pressure at 30 cmH2O for 30 seconds, were performed immediately after tracheal intubation. During surgery, the initial FIO2 was 50%. The FIO2 was increased until the subjects’ SpO2 was greater than 90%. The intraoperative ventilator settings, including VT, Ppeak, PEEP and FIO2, were recorded at T1 (10min after intubation), T2 (10min after pneumoperitonium), T3 (1 hour after pneunoperitonium + reverse trendelenburg position) and T4 (10min after non-pneumoperitonium). Blood gas analyses (PaO2 and PaCO2) were taken at T0 (before anesthesia induction), T1, T2, T3, T4, T5 (10min after tracheal extubation) and T6 (the 1st day after surgery). Heart rate (HR), mean blood pressure (MBP), SpO2 were also recorded from T0 to T5. Perioperative oxygenation index and respiratory dynamic compliance (Cdyn) during pneumoperitoneum were defined and calculated as follows: oxygenation index = PaO2 / FIO2; Cdyn = VT / (Ppeak-PEEP) [7]. On the 1st day after surgery, thoracic CT scanning was taken to identify the occurrence of abnormal radiographic changes (ARCs), such as infiltration, pleural effusion, ateclectasis and emphysema. The tracheal extubation time and the incidence of PPCs were also recorded including pneumonia, tracheal reintubation, respiratory failure, and death prior to discharge.
In the current research, the subjects’ respiratory Cdyn during pneumoperitoneum was the primary study endpoint. According to our pilot study, the Cdyn value in PCV group was 32.04 ± 7.13 ml/cmH2O. We hypothesized that the PCV-VG mode could improve Cdyn from 32 ml/cmH2O to 37ml/cmH2O. Forty-three subjects per arm (86 total) should be recruited with 90% power to detect the difference of 5 ml/cmH2O in Cdyn between the two ventilation modes (PCV and PCV-VG) at a level of 0.05 significance. Equal variances of 5 ml/cmH2O were assumed in this study. Accounting for 20% loss to follow-up, at least 52 subjects (104 total) should be enrolled per group.
Skewness/Kurtosis test were used to check normal distribution for all continuous variables. Normal distributing variables were reported by means ± standard deviation (SD), and compared by Student t-test. Non-normal distributing variables were presented by median (interquartile ranges) and compared by Wilcoxon rank-sum test. The incidence of PPCs (binary variables) were reported as proportion and compared with Fisher’s exact test. The related factors of postoperative extubation time was identified by Spearman correlation coefficient test, and adjusted by multiple linear regression. The results were presented by coefficient with 95% confidence intervals (CI) and adjusted P values. The multivariable logistic regression analyses were used for the risk factors of postoperative pneumonia and ARCs. The results were presented by odds ratio with 95% CI and P values. The confounders, such as age, gender, BMI, surgical duration, were adjusted by logistic regression analyses. A P value of < 0.05 was considered significant. All analyses were carried out in STATA14.1 (STATA Corp, USA).
There were 146 subjects undergoing bariatric surgery in our hospital between January 2018 and March 2020. According to the inclusion and exclusion criteria, 110 subjects were finally randomly divided and analyzed in one of the two groups: PCV-VG group (n = 56) or PCV group (n = 54, Fig. 1). There was no significant difference in gender, age, weight, height, BMI, duration of anesthesia and surgery between the two groups (Table 1).
| Variables | Total patients | PCV-VG | PCV | P value |
|---|---|---|---|---|
| (n = 110) | (n = 56) | (n = 54) | ||
| Male | 78 (70.9%) | 41 (73.2%) | 37 (68.5%) | 0.588 |
| Age, y | 31.4 ± 9.8 | 32.7 ± 10.3 | 30.2 ± 9.2 | 0.173 |
| ≤ 30y | 58 (52.7%) | 29 (51.8%) | 29 (53.7%) | |
| > 30y | 52 (47.3%) | 27 (48.2%) | 25 (46.3%) | |
| Weight, kg | 109.6 ± 20.9 | 110.2 ± 23.0 | 109.0 ± 18.7 | 0.777 |
| Height, cm | 167.7 ± 8.0 | 167.4 ± 7.2 | 167.0 ± 8.7 | 0.710 |
| BMI, kg/m2 | 38.8 ± 6.3 | 39.1 ± 7.2 | 38.6 ± 5.2 | 0.627 |
| < 40 | 72 (65.5%) | 37 (66.1%) | 35 (64.8%) | |
| ≥ 40 | 38 (34.5%) | 19 (33.9%) | 19 (35.2%) | |
| Anesthesia duration, min | 141.7 ± 25.8 | 140.3 ± 26.4 | 143.2 ± 25.5 | 0.566 |
| ≤ 2h | 19 (17.3%) | 9 (16.1%) | 10 (18.5%) | |
| > 2h | 91 (82.7%) | 47 (83.9%) | 44 (81.5%) | |
| Surgical duration, min | 110.9 ± 23.1 | 108.0 ± 23.5 | 112.9 ± 22.8 | 0.371 |
| ≤ 2h | 81 (73.6%) | 43 (76.8%) | 38 (67.9%) | |
| > 2h | 29 (26.4%) | 13 (23.2%) | 16 (29.6%) | |
| Table notes: Data are presented as No.(%) of patients or mean ± standard deviation. PCV-VG, pressure-controlled ventilation - volume guaranteed; PCV, pressure-controlled ventilation; BMI, body mass index. | ||||
The data revealed that there were no significant differences in terms of perioperative oxygenation index and Ppeak between the two groups. Compared with those in the PCV group, the Cdyn was significantly lower at T2 (10 min after pneumoperitoneum, P = 0.022) and T3 (1 hour after pneumoperitoneum, P = 0.039) in the PCV-VG group (Fig. 2).
The medium postoperative extubation time was 31 minutes in total 110 subjects. The postoperative lung CT scan revealed 86 subjects (78.2%) with abnormal imaging changes, including 72 cases (65.5%) with infiltration, 56 cases (50.9%) with pleural effusion, 9 subjects (8.2%) with atelectasis, and one subject with emphysema. After surgery, 10 subjects (9.1%) experienced pneumonia, no reintubation, respiratory failure or death occurred in either group. There was no significant difference in terms of extubation time, ARCs or PPCs between the two groups (Supplementary Table 1).
We analyzed the factors that might be related to the postoperative extubation time. The results showed that BMI, anesthesia duration, and oxygenation index (T0 and T3) were significantly correlated with extubation time. After adjustment, only anesthesia duration and oxygenation index (T0) had significant associations with extubation time ( Fig. 3 and Table 2).
| Variables | Spearman's rho | unjusted P value | adjusted P value | Coef. | SE | 95% CI |
|---|---|---|---|---|---|---|
| Age, y | 0.119 | 0.215 | 0.384 | 0.119 | 0.136 | -0.151 to 0.390 |
| BMI, kg/m2 | 0.192 | 0.044* | 0.35 | 0.22 | 0.234 | -0.244 to 0.684 |
| Anesthesia duration, min | 0.279 | 0.003** | 0.035* | 0.105 | 0.049 | 0.007 to 0.203 |
| Oxygenation Index (T0) | -0.291 | 0.002** | 0.009** | -0.055 | 0.021 | -0.096 to -0.014 |
| Oxygenation Index (T3) | -0.242 | 0.011* | 0.207 | -0.018 | 0.014 | -0.046 to 0.010 |
| Ppeak (T3) | 0.11 | 0.255 | 0.108 | -1.422 | 0.877 | -3.161 to 0.316 |
| Cdyn (T3) | -0.045 | 0.642 | 0.089 | -0.397 | 0.231 | -0.856 to 0.061 |
| Table notes: * P < 0.05; ** P < 0.01. BMI, body mass index; Ppeak, peak pressures; Cdyn, dynamic compliance; T0, before anesthesia induction; T3, 1 hour after pneunoperitonium. | ||||||
Furthermore, the multiple logistic regression analyses showed that anesthesia duration more than 2 hours increased the risk of postoperative ARCs (odds ratio 3.35, 95% CI 1.02 ~ 10.99, P = 0.046), compared with anesthesia duration less than 2 hours. Oxygenation index at T0 (before anesthesia induction) slightly decreased the risk of postoperative ARCs (odds ratio 0.99, 95% CI 0.98 ~ 0.99, P = 0.032). Ventilation mode, age, gender, BMI, oxygenation index, Ppeak and Cdyn during pneumoperitoneum were not risk factors of postoperative ARCs (Supplementary Table 2). And none of the above factors are risk factors of postoperative pneumonia (Supplementary Table 3).
Since recent two decades, the prevalence of obesity has dramatically increased in China, accompanied by a concurrent increase in weight-loss surgery. Laparoscopic sleeve gastroplasty, one of the bariatric surgical approaches, has been routinely performed with minimally invasive treatment and rapid recovery. However, compared with normal-weight population, obese subjects experience lower respiratory compliance during and after surgery, characterized by reduction in lung volume and increases in total respiratory resistance [5]. Intraoperative pneumoperitoneum can further decrease respiratory compliance due to altered pulmonary mechanics. Therefore, bariatric surgery put these obese subjects at a higher risk for PPCs such as pneumonia, tracheal reintubation, respiratory failure, or death [8]. In the current study, 78.2% subjects presented postoperative pulmonary radiographic abnormalities including infiltration, pleural effusion, ateclectasis or emphysema. Among them, 9.1% of subjects developed pneumonia after surgery. Consequently, optimal perioperative ventilation strategies are urgently needed for the obese population undergoing laparoscopic surgery.
There have been many reports on the comparison of different ventilation modes, such as VCV, PCV or PCV-VG, in obese subjects undergoing weight loss surgery. The studies by Cadi P and Ghodraty MR et al. found that the PCV mode achieved greater oxygenation (the PaO2/FiO2 ratio) than the VCV mode [9, 10]. A prospective cross-over cohort trial (n = 20) was conducted to compare the three ventilation modes in adolescents and young adults undergoing laparoscopic bariatric surgery, the results revealed that PCV-VG and PCV modes were both superior to VCV mode by providing ventilation with lower peak inflating pressure (PIP) [11]. In the current study, we compared the PCV-VG and PCV modes in adult subjects undergoing elective LGS. Our data showed that there was no significant difference in intraoperative oxygenation or airway Ppeak between the PCV-VG and PCV groups, which is consistent with the study by Michalsky M et al [11]. However, PCV mode provided ventilation with better pulmonary compliance than PCV-VG mode during pneumoperitoneum, which seems to contradict our previous hypothesis that PCV-VG mode integrates the advantages of both VCV and PCV and provides superior ventilation to PCV mode. The possible reason is that anesthesiologists were more vigilant about hypoventilation or hyperventilation caused by PCV mode in this study than routine clinical practice. The anesthesiologists adjusted the pressure settings in time based on the wide range of VT fluctuations during laparoscopic surgery. According to the results, PCV-VG mode is not superior to PCV mode on perioperative oxygenation and respiratory mechanics in obese subjects undergoing laparoscopic procedures.
Although the anesthesia time of bariatric surgery was relatively short (141.7 ± 25.8min) in the current study, our results revealed that anesthesia time of more than 2 hours would be a risk factor for postoperative extubation time and ARCs. Accumulation of anesthetics and long duration of mechanical ventilation are possible reasons for the prolonged extubation time. The results indicated that prolonged mechanical ventilation would increase the risk of PPCs, regardless of the ventilation modes. Accumulative evidence has revealed the association between prolonged mechanical ventilation and ventilator-induced lung injury (VILI) [12, 13], which is consistent with our results.
Limitations: 1) In this study, the respiratory compliance during intraoperative pneumoperitoneum was used as the primary study endpoint to calculate the sample size, which may not be power enough to detect the difference in extubation time, PPCs or ARCs between the two groups. To compare the PPCs between the PCV and PCV-VG group, a larger sample size might be required for verification. 2) Morbid obesity (BMI > 40 kg/m2) is an independent risk factor for PPCs [14]. However, in the current study, the mean BMI of the included subjects was 38.8 ± 6.3 kg/m2, and most of the subjects did not reach the level of morbid obesity. Consequently, the study cannot evaluate the impacts of two ventilation mode on perioperative oxygenation and respiratory mechanics in subjects with morbid obesity. Also, the study cannot confirm the association between morbid obesity and PPCs. 3) In our hospital, reverse Trendelenburg position is routinely used in bariatric surgery. This specific subject position improves perioperative respiratory mechanic by counteracting pneumoperitoneum-induced restrictive ventilation dysfunction. Therefore, our results are not proper to be explored in obese subjects undergoing other laparoscopic surgery with different subject positions, such as gastrointestinal operation in the supine position, or gynecological surgery in the Trendelenburg position.
In patients undergoing laparoscopic bariatric surgery, the PCV mode provided better pulmonary compliance compared to the PCV-VG mode. There was no difference in perioperative oxygenation between the two ventilation modes. Further large-sample studies are needed to determine the optimal ventilation mode in terms of PPCs in obese patients undergoing laparoscopic surgery.
Ethics approval and consent to participate
The protocol of this study was approved by the Ethical Review Committee of Huashan Hospital, Fudan University (No.2016-397) and registered on ClinicalTrials.gov (NCT03150264, 12/05/2017). We declare that all of the procedures relevant to this experiment were performed in accordance with the guidelines and regulations of the Ethical Review Committee of Huashan Hospital, Fudan University, and all subjects were given written informed consent to participate.
Consent for publication
Not Applicable.
Availability of data and materials
The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
Competing interests
No potential conflict of interest relevant to this article was reported.
Funding
This work was supported by Natural Science Foundation of China (No. 82171188) to Qiong Yu. The aforementioned funding bodies had no role in study design and data collection, analysis, and interpretation, preparation of manuscript or the decision to submit for publication.
Authors' contributions
Q.Y. contributed to the funding for the study, together for data collection, while R.H. were responsible for the study design and manuscript preparation. Z.Z and P.W. were responsible for analysis and interpretation of the results and manuscript preparation. The manuscript was revised and approved for publication by all authors involved.
Acknowledgments
Not Applicable.
Contributor Information
Zhengyu Zhou, Email: [email protected].
Pan Wu, Email: [email protected].
Rong Hua, Email: [email protected]. Tel:+8613621750603.
Qiong Yu, Email: [email protected]. Tel:+8613472755168.