The fraction of Nitrous Oxide in oxygen for facilitating Lung collapse During One-Lung Ventilation with double lumen tube

doi:10.21203/rs.3.rs-16105/v1

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The fraction of Nitrous Oxide in oxygen for facilitating Lung collapse During One-Lung Ventilation with double lumen tube

https://doi.org/10.21203/rs.3.rs-16105/v1

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published 22 Jul, 2020

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Backgroud To the best of our knowledge, it is still unclear what is the proper fraction of nitrous oxide(N 2 O) in oxygen(O 2 ) for fast lung collapse. Therefore, we designed this prospective trial to determine the 50% effective concentration (EC 50 ) and 95% effective concentration (EC 95 ) of N 2 O in O 2 for fast lung collapse.

Methods We studied 38 consecutive patients undergoing video-assisted thoracoscopic surgery(VATS). The lung collapse score(LCS) of each patient during one lung ventilation was evaluated by the same surgeon. The first patient received 30% N 2 O in O 2 , and subsequent N 2 O fraction in O 2 was determined by the LCS of previous patient using Dixon up-and-down method. The testing interval was set at 10%, and the lowest concentration was 10% (10%, 20%, 30%, 40%, or 50%). The EC 50 and EC 95 of N 2 O in O 2 for fast lung collapse were analyzed using probit test.

Results The N 2 O fraction in O 2 at which all patients showed success lung collapse was 50%, according to the up-and-down method. The EC 50 and EC 95 of N 2 O in O 2 for fast lung collapse were 27.7% (95% confidence interval, 19.9%–35.7%) and 48.7% (95% confidence interval, 39.0%–96.3%), respectively.

Conclusions In patients undergoing VATS, the EC 50 and EC 95 of N 2 O in O 2 for fast lung collapse were 27.7% and 48.7%, respectively.

Anesthesiology & Pain Medicine

Nitrous Oxide

Lung collapse

One-Lung Ventilation

double lumen

Fast lung collapse facilitates intrathoracic surgical procedures which is particularly important in minimally invasive video-assisted thoracoscopic surgery(VATS). It is well known that when one-lung ventilation(OLV)begins, the nonventilated lung will undergo Phase I lung collapse due to the elastic recoil, which occurs within 60 seconds.[1] When the Phase I lung collapse ceases, presumably due to small airway closure, the slower Phase II lung collapse begins, which is mainly depends on continuous gaseous diffusion or absorption atelectasis. The previous recommended measures for hastening lung collapse include insufflating carbon dioxide into the pleural space[1]and intermittent airway suction[2]. However, no reported studies indicate that these measures achieve the intended result.

The rate of gas absorption in nonventilated lung depends on the inspired gas composition[3, 4]. Oxygen(O₂) fraction and the solubility of any inert gas in the inspired mixture are important factors for the rate of gas absorption. If the inspired gas mixture contains less soluble gas such as nitrogen, the absorption rate is relatively slow and increases as O₂ increases[4]. In contrast, when the inspired mixture contains a relatively soluble inert gas and O₂, gas absorption is faster. Nitrous oxide(N₂O) is highly soluble in physiological terms. In animal models[5, 6], it has been demonstrated that mechanical lung ventilation with an O₂/N₂O mixture will increase the rate of gaseous uptake from the non-ventilated lung and so hasten its absorptive collapse. In addition, clinical studies also indicated that compare to O₂/air mixture or 100% O₂, by using O₂/N₂O mixture before OLV prompt Phase II lung collapse when a double-lumen tube (DLT) or bronchial blocker(b-blocker) was used for lung isolation. Furthermore, this useful measure does not affect Phase I lung collapse and cause hypoxia[7–9].

The commonly used N₂O fraction in O₂ for fast lung collapse was 50% or 60%[6–8], however, it is still unclear what is the proper fraction of N₂O in O₂ when this measure was used in thoracic procedures. Therefore, we designed this prospective trial to determine the 50% effective concentration (EC₅₀) and 95% effective concentration (EC₉₅) of N₂O in O₂ for fast lung collapse. The primary outcome of the current study was to investigate the lung collapse score (LCS) at 5 minutes after opening the thorax (Phase II lung collapse), by using a “up and down” method, EC₅₀ and EC₉₅ of N₂O in O₂ for fast lung collapse was calculated.

This study was approved by the Institutional Review Board of Zhongshan Hospital, Fudan University (IRB:B2018-314R) and written informed consent was obtained from all subjects participating in the trial. The trial was registered prior to patient enrollment at http://www.chictr.org/cn/( ChiCTR19 00021474, Principal investigator: Chao Liang, Date of registration: 2-22-2019).Patients in zhongshan hospital scheduled for elective VATS for lung cancer were enrolled in present study. All patients had preoperative pulmonary function tests. Patients who had evidence of bullae on chest radiographs, abnormal expiratory recoil (Forced expiratory volume at 1 second (FEV₁) < 70% of predicted value), chronic obstructive pulmonary disease or severe asthma, major medical co-morbidities and anticipated pleural adhesion were excluded.

To avoid the potential effects of inhaled volatile anesthetic on oxygenation during OLV, all patients received total IV anesthesia. Propofol was administered via a target-controlled infusion (TCI) device (Cardinal Health, Basingstoke, UK), which used a three-compartment population pharmacokinetic model defined by Schnider et al.[10]Anesthesia was induced with propofol TCI (target plasma concentration was set at 4.0 µg ml^− 1), remifentanil (0.2 µg kg^− 1min^− 1), fentanyl 1 µg kg^− 1, and rocuronium bromide 0.6 mg kg^− 1. Anesthesia was maintained with propofol TCI(target plasma concentration was set at 3.0 µg ml^− 1) infusion and intermittent boluses rocuronium. Tidal volumes were 8 ml kg^− 1 ideal body weight during both 2LV and OLV without positive end expiratory pressure. The 100% O₂ was introduced by mask during induction. An appropriate-size left-sided double-lumen endobronchial tube (DLT) was intubated and the position of the DLT was confirmed with fiberoptic bronchoscopy (FOB). Then the selected gas mixture was introduced and continued during positive pressure ventilation until the start of OLV. The patients were turned to the lateral position and the position of the DLT was reconfirmed and adjusted as needed by FOB. At the time of skin incision, the DLT lumens were opened to atmosphere for 60 s and then the nonventilated lumen of DLT was clamped for gas uptake, and OLV of the dependent lung was begun with a Fraction of inspired oxygen equal to1.0.

Measurement

Given all cases were conducted by video-assisted surgical technique, lung collapse was scored via video view. Surgeons blinded to the gas composition assessing the LCS at 5 minutes after pleural opening by using a verbal rating scale[7] from 0 (no lung deflation) up to 10 (maximal lung collapse). The FOB was used to diagnose and correct the problem when lung isolation was not satisfactory. Baseline arterial blood gas of each patient was obtained preoperatively while patients breathed room air, after anesthesia induction, the right or left radial artery was cannulated, and blood gas samples were analyzed every 10 minutes for the first 30 minutes of OLV. The lowest SpO₂ during OLV and the time required to open the lung pleura (time from start of one lung ventilation until pleural opening), end-tidal carbon dioxide, heart rate, and arterial blood pressure were also recorded. End-tidal O₂ or N₂O was recored every minute from the start of OLV by using the anesthetic analyzer embedded in anesthesia machine. (IntelliVue G5, Phillips, Andover, MA).

To calculate the EC₅₀ and EC₉₅ of N₂O in O₂, the N₂O fraction in O₂ of first case was 30%, and the subsequent N₂O fraction were determined by the LCS of the previous patient using Dixon up-and-down method. The testing interval was set at 10%, and the lowest concentration of N₂O was 10%. The “successful lung collapse” was defined as patient’s LCS more than or equal to 8, and the N₂O fraction of the subsequent patient was decreased by 10%.The LCS less than 8 was regarded as “failed”, and the N₂O fraction of the subsequent patient was increased by 10%.

Statistical analysis

Statistical analysis was performed by use of SPSS version 19.0 software (IBM, Armonk, NY, USA) and Excel 2007 (Microsoft, Redmond, WA, USA). Patients’ characteristics are presented as mean and SD or number. Continuous variables were analysed by t-test and categorical variables were analysed by x² test. The mean of mid-point of all failed/success pairs were used to calculate N₂O EC₅₀ using Dixon and Massey's up and down method, and a minimum of 8 crossover pairs were required for the analysis[11]. Dose-response curve was determined using probit analysis and interpolation was done to obtain EC₅₀ and EC₉₅ with 95% confidence intervals (CI).

We assessed eligibility of 40 patients and finally 38 eligible patients were recruited in the study (Fig. 1). All patients had satisfactory lung isolation and did not require correction of DLT malpositioning or discontinuation of OLV. Two patients had pneumothoracic adhesions which were difficult for scoring the lung collapse condition and were excluded from the study, and finally 36 patients were analysed. Demographic characteristics of the patients are presented in Table 1.

Table 1 Demographic data of study population

American Society of Anesthesiologists	2(1-3)
Age(y)	52.5±9.2
Gender(male/female)	19/17
Weight(kg)	57.6±9.2
Height(cm)	157±8.6
^aPleural opening(s)	59.6±12.2
FEV1 (% of predicted)	84.6±12.2
FVC (% of predicted)	82.3±9.2
FEV1/FVC	80.2±8.8
Surgery type VATS-R VATS-L	20 16

FEV1 = forced expiratory volume at 1 second; FVC = forced
vital capacity.
^aTime from incision to pleural opening.
VATS = video-assisted thoracoscopic surgery

The N₂O fraction-success data of lung collapse scoring for patient obtained by the up-down method are presented in Fig. 2. This was further analysed by Probit Regression Analysis. The EC₅₀ of N₂O in O₂ for fast lung collapse was 27.7% (95% CI, 19.9–35.7%). The EC₉₅ of N₂O in O₂ for fast lung collapse was 48.7% (95% CI, 39.0–96.3%). Table 2 shows N₂O fraction in O₂ and Percentages of patients who had successful LCS (lung collapse score equal to or more than 8). The fraction-success curve of N₂O plotted from probit analysis of individual N₂O fraction and the respective LCS is presented in Fig. 3. Clinically significant desaturation (SpO₂ < 90%) requiring alveolar recruitment maneuvers or other interventions did not occur in any patient.

Table 2 Percentages of patients who had successful lung collapse score (lung collapse score equal to or more than 8)

Nitrous oxide fraction in each subgroup (%)	Success rate
10	0% (0/3)
20	25% (3/12)
30	68% (9/13)
40	67% (4/6)
50	100% (2/2)

The measure of using O₂/N₂O mixture is a useful way for fast lung collapse. This study further determined the EC₅₀ of N₂O in O₂ for fast lung collapse. The results from present study showed that the EC₅₀ of N₂O in O₂ for fast lung collapse was 27.7%.

The underlying mechanism of N₂O/O₂ inspired gas mixture leads to fast lung collapse may attributed to a “second gas” effect, which is the rapid absorption of N₂O facilitates O₂ uptake, or to a concentration effect or to the gas solubility[12]. During OLV, the nonventilated lung collapses initially due to elastic recoil and the remaining gas is then removed by absorption into the pulmonary capillary blood[6]. Thus, in present study, for the complete lung collapse by elastic recoil, both nonventilated and ventilated lumens of DLT were opened to atmosphere for 60 s, and then the nonventilated lumen of DLT was clamped for gas uptake. The average time of plural opening in present study was around 60 s(59.6 ± 12.2 s), which is consistent with the former studies reported for plural opening of VATS[7]. Then a verbal rating scale[7, 8] from 0 (no lung deflation) up to 10 (maximal lung collapse) was used by surgeon for scoring the patient’s lung collapse condition. There are also other studies[13, 14] used a four-point ordinal scale(1, extremely poor-no collapse of lung; 2, poor-partial collapse with interference with surgical exposure; 3, good-total collapse, but the lung still had residual air; and 4, excellent-complete collapse with perfect surgical exposure.) to evaluate the lung condition, however, defining a “success” and “failed” condition is the necessary step for determining EC₅₀ by up and down method. Compare to the four-point ordinal scale, the verbal rating scale from 0 to 10 seems more accurate for scoring patient lung collapse condition. Moreover, in our plot study, almost all surgeons regarded LCS equal to or more than 8 as a proper condition for lung manipulations, and we thus defined LCS equal to or more than 8 as “success” and less than 8 as “failed”.

In the study of b-blocker as a lung isolation tool, the LCS of 50% N₂O in O₂ was significantly higher compared with that of 100% O₂ at 5 minutes after opening the pleura, however, there were still less than 50% patients’ LCS was more than or equal to 8[7]. In another study which DLT was used as the lung isolation tool, when 50% N₂O was applied, the average LCS was 9 at 10 minutes after opening the pleura, although these investigators did not observe LCS at 5 minutes after opening the pleura[8]. In our plot study, when 30% N₂O in O₂ was used, about 50% patients’ LCS was more than or equal to 8. The differences of LCS at 5 minutes after opening the pleura between our study and the study of b-blocker as the lung isolation tool may largely attributed to the different isolation tools and the surgeon’s personal LCS scoring criteria.

In these former studies[7, 8], the target gas mixtures of N₂O and O₂ were used at the time of preoxygenation during anesthesia induction, and the gas concentrations before OLV were equal to the target ones. While in present study, 100% O₂ was used for preoxygenation, and then the selected gas mixtures of N₂O and O₂ were used after intubation. However, before OLV, all selected gas mixture of N₂O and O₂ were equal to the target ones. Therefore, it seems that using O₂ for induction, and switch to N₂O and O₂ after intubation is more applicable, since a “more O₂ induction period” is safer that less one. For the operation type, all cases in the present study underwent VATS for lung surgery, which is the main surgery type for lung tumor, and the enrolled cases in these former studies mainly underwent open thoracotomies. Compare to the open thoracotomies, the lung collapse condition is more important for the VATS, and thus the data from present study is more applicable for modern clinical practice.

The present study has several limitations. First, for the purposes of this study, we determined the success or failure of lung collapse based on surgeons’ scoring scale, which was not completely objective. However, like the methods used in previous studies, using a more objective criteria such as the distance of the collapsed lung to the chest wall seems less clinically relevant due to the different sizes of the patients’ chests. Therefore, the most clinically relevant assessment of lung collapse condition is the surgeon’s impression. Secondly, all patients in present study had relative normal pulmonary function tests and body mass indices, the results of our study might not be applicable to the patients with poor pulmonary function tests or obesity. And these concerns are the objectives of our future study.

In conclusion, in patients undergoing VATS, when the double lumen tube was used for lung isolation, the EC₅₀ of N₂O during 2LV for accelerating lung collapse during OLV was 27.7%.

N2O:nitrous oxide;O2:oxygen;EC50: 50% effective concentration;EC95:95% effective concentration; VATS: video-assisted thoracoscopic surgery;LCS:lung collapse score; OLV;one-lung ventilation; DLT:double-lumen tube; b-blocker:bronchial blocker; FEV1: Forced expiratory volume at 1 second; TCI:target-controlled infusion; FOB:fiberoptic bronchoscopy; CI:confidence intervals

Acknowledgements

Not applicable.

Funding

This work was supported by the Natural Science Foundation of China (Grant no. 81400930)

Availability of data and materials

Reasonable requests for access to the datasets used and/or analysed during this study can be made to the corresponding author

Authors’ contributions

YC L and CL conceived and designed the study, collecting and interpretation of data, and drafting the manuscript. YS carried out the statistical analysis, and was involved in interpretation of data and drafting the manuscript. CJ and ZG X was involved in designing the study, and was involved in interpretation of data and drafting the manuscript. All of the authors critically revised and approved the final form of the manuscript.

Ethics approval and consent to participate

This study was approved (IRB:B2018-314R) by the Ethics Committee of Zhongshan Hospital, Fudan University on Dec 4, 2018. All of the participants gave their written, informed consent to participate in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Landreneau RJ, Mack MJ, Hazelrigg SR, Dowling RD, Acuff TE, Magee MJ, Ferson PF: Video-assisted thoracic surgery: basic technical concepts and intercostal approach strategies. Ann Thorac Surg 1992, 54(4):800-807.
Baraka A: Hazards of carbon dioxide insufflation during thoracoscopy. British journal of anaesthesia 1998, 81(1):100.
Dale WA, Rahn H: Rate of gas absorption during atelectasis. Am J Physiol 1952, 170(3):606-613.
Joyce CJ, Baker AB, Kennedy RR: Gas uptake from an unventilated area of lung: computer model of absorption atelectasis. J Appl Physiol (1985) 1993, 74(3):1107-1116.
Joyce CJ, Baker AB, Parkinson R, Zacharias M: Nitrous oxide and the rate of gas uptake from an unventilated lung in dogs. British journal of anaesthesia 1996, 76(2):292-296.
Pfitzner J, Peacock MJ, Pfitzner L: Speed of collapse of the non-ventilated lung during one-lung anaesthesia: the effects of the use of nitrous oxide in sheep. Anaesthesia 2001, 56(10):933-939.
Yoshimura T, Ueda K, Kakinuma A, Sawai J, Nakata Y: Bronchial blocker lung collapse technique: nitrous oxide for facilitating lung collapse during one-lung ventilation with a bronchial blocker. Anesthesia and analgesia 2014, 118(3):666-670.
Ko R, McRae K, Darling G, Waddell TK, McGlade D, Cheung K, Katz J, Slinger P: The use of air in the inspired gas mixture during two-lung ventilation delays lung collapse during one-lung ventilation. Anesthesia and analgesia 2009, 108(4):1092-1096.
Joyce CJ, Baker AB: What is the role of absorption atelectasis in the genesis of perioperative pulmonary collapse? Anaesthesia and intensive care 1995, 23(6):691-696.
Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, Youngs EJ: The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology 1998, 88(5):1170-1182.
Dixon WJ: Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev 1991, 15(1):47-50.
Pfitzner J, Peacock MJ, Harris RJ: Speed of collapse of the non-ventilated lung during single-lung ventilation for thoracoscopic surgery: the effect of transient increases in pleural pressure on the venting of gas from the non-ventilated lung. Anaesthesia 2001, 56(10):940-946.
El-Tahan MR: A comparison of the disconnection technique with continuous bronchial suction for lung deflation when using the Arndt endobronchial blocker during video-assisted thoracoscopy: A randomised trial. Eur J Anaesthesiol 2015, 32(6):411-417.
Li Q, Zhang X, Wu J, Xu M: Two-minute disconnection technique with a double-lumen tube to speed the collapse of the non-ventilated lung for one-lung ventilation in thoracoscopic surgery. BMC Anesthesiol 2017, 17(1):80.

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The fraction of Nitrous Oxide in oxygen for facilitating Lung collapse During One-Lung Ventilation with double lumen tube

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