Effects of different fractions of inspired oxygen on gas embolization during hysteroscopic surgery: A double-blind randomized controlled trial

doi:10.21203/rs.3.rs-1833630/v1

Background

Gas embolism is a common complication of hysteroscopic surgery, which causes serious concern among gynecologists and anesthesiologists due to the potential risk to the patients. The influencing factors of gas embolism in hysteroscopic surgery have been extensively studied. However, the effect of the oxygen concentration inhaled by patients on gas embolism during hysteroscopic surgery remains elusive. So, we designed a double-blind randomized controlled trial to determine whether different inhaled oxygen concentrations influence the occurrence of gas embolism during hysteroscopic surgery.

Methods

This prospective, double-blind, randomized controlled trial enrolled 162 adult patients aged between 20 and 65 years undergoing elective hysteroscopic surgery who were randomly divided into three groups with fractions of inspired oxygen of 30%, 50% and 100%. Transthoracic echocardiography (4-chamber view) was used to evaluate whether the gas embolism occurred. Before the start of surgery, 4-chamber view was continuously monitored.

Results

The number of gas embolism in group A, B and C was 36 (69.2%), 30 (55.6%) and 24 (44.4%) respectively. The incidence of gas embolism gradually decreased with the increase of inhaled oxygen concentration(P=0.031).

Conclusions

In hysteroscopic surgery, a higher oxygen concentration inhaled by patients could reduce the incidence of gas embolism, indicating that a higher inhaled oxygen concentration, especially 100%, could be recommended for patients during hysteroscopic surgery.

Trial registration

Chinese Clinical Trial Registry(23/05/2020, ChiCTR2000033202)

hysteroscopic surgery

general anesthesia

oxygen concentration

gas embolism

transthoracic echocardiography

Hysteroscopic surgery is one of the most commonly performed minimally invasive procedure in clinical practice and is usually used to diagnose and treat endometrial polyps, intrauterine adhesions and subserous myoma¹. Although hysteroscopic surgery has been regarded as a safe and effective surgical procedure, it is still associated with some complications, including fluid overload syndrome and gas embolism (GE)². GE in particular causes serious concern among gynecologists and anesthesiologists because it can be insidious but deadly, and the treatment options are rather limited.

GE is a condition in which gas enters the blood vessels and causes a blockage that can lead to ischemia and hypoxia. Previous studies have shown that the incidence of GE during hysteroscopic surgery is 10%-50%^3,4. During hysteroscopic surgery, gases that enter the uterus during the dilation of the cervix, gases that are not drained from the instruments, and gases that are generated by vaporization of distention fluid can enter the bloodstream through damaged arteries and veins in the uterine cavity, causing GE⁵. Clinical symptoms vary from asymptomatic to cardiac arrest, depending on the amount of gas, speed of its entry into the blood vessel, and location of gas entry⁶. When bubbles reach the lung through the inferior vena cava, they can cause hypoxemia, pulmonary vasoconstriction, increased pulmonary artery pressure, and overload of the right ventricle, ultimately leading to heart failure⁴. In addition, gas entering the pulmonary arterioles can stimulate the release of histamine and serotonin, causing pulmonary edema^3,4,7. Therefore, effective prevention of GE during hysteroscopic surgery appears to be particularly important.

Previous studies on GE during hysteroscopic surgery have mainly focused on the incidence of GE; the influence of surgical location, surgical instruments, and anesthetics; and the monitoring of GE^5,7−10. Intriguingly, in our clinical observation, we found that GE did not occur when patients were administered 100% oxygen, but different degrees of GE occurred when 50% oxygen was inhaled with the same surgical instruments and surgical personnel. The effect of the oxygen concentration inhaled by patients on GE during hysteroscopic surgery remains elusive. Therefore, we hypothesize that the occurrence of GE is, to some extent, associated with the oxygen concentration inhaled by patients during hysteroscopic surgery.

Here, we designed a double-blind randomized controlled trial to determine whether different inhaled oxygen concentrations influence the occurrence of GE during hysteroscopic surgery.

This prospective, double-blind, randomised controlled trial was performed at West China Second Hospital of Sichuan University and approved by the Chinese Ethics Committee of Registering Clinical Trials (Chairperson Taixiang Wu, Reference number: ChiECRCT20210033) on 12 February 2021. It was prospectively registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000033202, principal investigator Xi Deng, registration date: 23 May 2020). The study has been approved by the institutional research ethics committee before experiment was started and that has been conducted in accordance with the principles set forth in the Helsinki Declaration.

After written informed consent was obtained from the patients, 162 adult patients aged between 20 and 65 years with an American Society of Anesthesiologists (ASA) status of I to III undergoing elective hysteroscopic surgery were recruited. The exclusion criteria included all types of heart disease, transfer to laparoscopic surgery, thrombotic disease, and refusal to undergo cardiac ultrasound.

After randomization using a digital table and opaque envelopes, patients were randomly assigned to group A, group B or group C, with inhaled oxygen concentrations of 30%, 50% and 100%, respectively. The data recorder, the analyst and the cardiac ultrasound researcher were blinded to the experimental grouping.

In the operating room, an 18-gauge cannula vein channel was established on the back of the right hand, and electrocardiogram(ECG), noninvasive blood pressure and saturation of pulse oxygen(SPO₂) were monitored. General anesthesia was induced with intravenous midazolam 1 mg, propofol 2 mg/kg and sufentanil 0.2 µg/kg. After inserting a laryngeal mask, we adjusted the inhaled oxygen concentration to 30% in group A, 50% in group B and 100% in group C. The tidal volume was 8–10 ml/kg. The ventilation frequency was 10–12 times/min. End-tidal carbon dioxide partial pressure (PetCO₂) was maintained at 35–45 mmHg. Sevoflurane (2%-3%) was administered for anesthesia maintenance. All operations were performed by the same surgeon. The experimental flow chart is shown in (Fig. 1).

Data collection

The demographic, clinical and intraoperative characteristics, including age, height, weight, ASA status, diagnosis, operative time, duration of GE, intrauterine pressure, amount of intravasation and oxygen concentration, were recorded.

The primary outcome was the incidence of GE. Transthoracic echocardiography (TTE, 4-chamber view) was used to evaluate whether the GE occurred, and the images (Fig. 2, Bubbles are indicated by the white arrows) of TTE were assessed as grade I to V (Table 1). Before the start of surgery, 4-chamber view was continuously monitored. The first record was made before the start of surgery. After the operation began, images were recorded every minute until the end of the operation. If there were bubbles, the image was recorded until the bubbles disappeared. In the clinical, a single bubble may be formed in the heart cavity during intravenous infusion or injection. Therefore, the TTE images of grade I-II can be regarded as no GE, otherwise the grade of III-V is regarded as GE.

Table 1

The definition of the grade of the TTE images
grade	Definition
I	Grade I was defined as no bubbles passing through the heart.
II	Grade II was defined as the presence of a single emboli in the RA or RV
III	Grade III was defined as gas emboli filling less than half the diameter of the RA or RV.
IV	Grade IV was defined as gas emboli filling more than half the diameter of the RA or RV.
V	Grade V was defined as gas emboli completely filling the diameter of the RA or RV, and even in the LA or LV.
RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.

The secondary outcomes included mean arterial blood pressure (MAP), heart rate (HR), PetCO₂ at the time of the most severe embolization, the duration of GE and hemodynamic instability. The most severe embolization is when the most bubbles are seen in the heart cavity, and the data recorder is informed by the personnel in charge of TTE.

The duration of GE was the period from the discovery of bubbles in the right atrium or ventricle to the disappearance of the bubbles. Cardiovascular disturbances probably resulting from GE are as follows: a sudden decrease in MAP by > 30% from baseline or a sudden decrease in PetCO₂ by > 20% from baseline or SPO₂ ≤ 95 or ST-segment change of more than 2 mm from baseline or bradycardia (HR < 60 bpm) and tachycardia (HR > 100 bpm). Hemodynamic instability was defined as the presence of at least two of these clinical signs. Severe GE was defined as grades IV-V.

Sample size calculation

According to the incidence of GE at different oxygen concentrations in the preliminary test, inhaled oxygen concentrations of 30% and 50% were compared with 100% inhaled oxygen. α was 0.025, β was 0.2. The final sample size was 52 cases in each group. To correct for a possible loss of patients, each group decided to include 54 patients.

Statistical analyses

Statistical analyses were performed with IBM SPSS Statistics version 26.0 software (IBM Corporation, USA). No interim analysis was planned. The data are presented as numbers and percentages or medians. The incidence of GE among the three groups was compared with the trend χ² test. Others were compared using the Kruskal–Wallis rank sum test and χ² test. P < 0.05 was considered statistically significant.

From May 2021 to November 2021, 160 patients were included and randomly divided into three groups: Group A (n = 52, 30% O₂), Group B (n = 54, 50% O₂) and Group C (n = 54, 100% O₂). There were no significant differences of demographic characteristics in height, age, weight, clinical diagnosis, ASA (Table 2), or of intraoperative characteristics in duration of operation, intrauterine pressure, amount of intravasation, duration of embolization, HR, MAP and PetCO₂ at the time of the most severe embolization (Table 3) among the three groups (P > 0.05).

Table 2

Demographic characteristics of the three groups
Group	Oxygen concentration(%)	age, y	height, cm	weight, kg	Diagnosis(myoma/IUA or uterus septum/others)	ASA(I/II/III)
A	30	33 [29 to 37.25]	157 [155 to 160]	52.5 [48 to 57.25]	4/34/14	45/7/0
B	50	34 [28.25 to 38.75]	160 [155.25 to 162]	52 [48 to 59.5]	10/24/20	50/3/1
C	100	32 [29 to 37.75]	160 [158 to 162]	53 [52 to 61]	7/27/20	52/2/0
P value		0.800	0.078	0.351	0.865	0.187
Data are median [IQR] or number. IUA, intrauterine adhesions.

Table 3

Intraoperative characteristics of the three groups of patients
Group	Oxygen concentration(%)	Operative time(min)	Intrauterine pressure(mmHg)	The amount of intravasation(ml)	Duration of GE(min)	HR(beats/min)	MAP(mmHg)	PetCO₂(mmHg)
A	30	18.5 [15 to 20]	110 [100 to 120]	200 [100 to 300]	10 [2.25 to 17.25]	65.5 [59 to 71]	76 [68 to 82]	34 [32 to 36]
B	50	20 [15 to 23.75]	100 [100 to 110]	175 [100 to 300]	8 [5 to 20]	65 [60 to 74]	74.5 [68 to 81]	33 [32 to 35]
C	100	16 [15 to 25]	100 [100 to 120]	200 [100 to 390]	8.5 [3.75 to 13.5]	64 [58 to 73]	73.5 [69 to 77]	34 [31 to 36]
P value		0.951	0.089	0.477	0.083	0.595	0.341	0.438
Data are median [IQR] or number. HR, MAP and PetCO₂ are the values corresponding to the maximum number of bubbles detected on cardiac ultrasound.

As shown in Table 4. The number of patients with TTE images of grade I-V were 3 (5.8%), 13 (25.0%), 17 (32.7%), 18 (34.6%), and 1 (1.9%) in group A (n = 52); 8 (14.8%), 16 (29.6%), 21 (38.9%), 7 (13.0%) and 2 (3.7%) in group B (n = 54); 13 (24.1%), 17 (31.5%), 14 (25.9%), 8 (14.8%) and 2 (3.7%) in group C (n = 54). We regarded images of grade I-II as the absence of GE, and grade III-V as the occurrence of gas embolism. As is shown in Table 5, the number of GE in group A, B, C was 36 (69.2%), 30 (55.6%) and 24 (44.4%) respectively. The incidence of GE gradually decreased with the increase of inhaled oxygen concentration. There was significant difference between three groups(P = 0.031).

Table 4

The proportions of different grade of the TTE images in the three groups
Group	A (30%)	B (50%)
Grade I	3 (5.8)	8 (14.8)	13 (24.1)
Grade II	13 (25.0)	16 (29.6)	17 (31.5)
Grade III	17 (32.7)	21 (38.9)	14 (25.9)
Grade IV	18 (34.6)	7 (13.0)	8 (14.8)
Grade V	1 (1.9)	2 (3.7)	2 (3.7)
Data are number (%).

Table 5

The incidence of gas embolism in the three groups
Gas Embolism	Yes	No	P for trend
			0.031^*
Group A (30%)	36 (69.2)	16 (30.8)
Group B (50%)	30 (55.6)	24 (44.4)
Group C (100%)	24 (44.4)	30 (55.6)
Data are number (%). We compared three groups with trend χ² test. *There was significant difference between three groups(P < 0.05).

Among the 160 patients, 6 patients showed clinical symptoms of GE. The number of patients in each group who experienced changes in vital signs is shown in Table 6. The number of hemodynamic instability in group A, B, C was 0, 2(3.7%) and 1(1.8%), respectively. 1 patient in group C had ventricular arrhythmia. All of the patients with GE showed a drop in PetCO₂. Paradoxical embolism was observed in one patient in group B. The patient also had ST-segment depression and decreased oxygen saturation. TTE showed a large number of air bubbles in the LA and LV.

Table 6

Clinical parameters changes that might be the result of the gas embolism
Variables	Group A (n = 52)	Group B (n = 54)	Group C (n = 54)
PetCO₂ drop > 20%	1 (1.9)	2 (3.7)	2 (3.7)
SPO₂ ≤ 95	0	1 (1.8)	0
MAP drop > 30%	0	2 (3.7)	2 (3.7)
Bradycardia or tachycardia	0	1 (1.8)	2 (3.7)
ST-segment depression > 2 mm	0	1 (1.8)	0
Hemodynamic instability	0	2 (3.7)	1 (1.8)
Data are number (%).ST-segment, electrocardiographic change.

In the present study, the influence of different inhaled oxygen concentrations on the incidence of GE during hysteroscopic surgery were investigated. We found that with the increase of inhaled oxygen concentration, the incidence of GE decreased. This suggests that higher inhaled oxygen concentrations may reduce the incidence of GE during hysteroscopic surgery.

Three inhaled oxygen concentrations, 30%, 50% and 100%, were selected in our study for the following reasons. First, according to Miller’s anesthesia, impaired blood oxygenation occurs in most people under anesthesia, so it is common practice to increase the inhaled oxygen concentration appropriately, usually by 30–50%¹¹. In addition, more than one study of perioperative oxygen concentration has used a minimum oxygen concentration of 30%^12,13. Therefore, to ensure the oxygenation function of patients and to be as close to the oxygen concentration in the air as possible, we chose an oxygen concentration of 30%. Second, in our clinical practice, we usually use two liters of fresh gas and set the inhaled oxygen concentration of the anesthesia machine to 50%, so a 50% oxygen concentration was also included in the study. Finally, to investigate whether 100% inhaled oxygen concentration could reduce the incidence of GE during hysteroscopic surgery, an oxygen concentration of 100% was selected for the study. However, studies have shown that high inspired oxygen fractions cause rapid absorption of gas behind closed airways, resulting in atelectasis^14,15. With the increase in inhaled oxygen concentration, hypoxic pulmonary vasoconstriction weakens, and atelectasis further develops ¹⁶. In our study, the surgery time was usually no longer than 25 min, which caused the atelectasis resulting from high inspired oxygen appear to be negligible, indicating that the high inspired oxygen concentration in our study was safe for the patients. In addition, a vital capacity maneuver was used to prevent atelectasis in each patient after surgery.

The incidence of GE at 30%, 50%, and 100% inhaled oxygen was gradually reduced, perhaps because a higher oxygen concentration facilitated oxygenation, which could not only treat hypoxemia but also establish a diffusion gradient conducive to gas bubble outflow^17,18. In addition, a high oxygen concentration can accelerate the oxygen entry into the bubble, promoting the exit of nitrogen from the bubble so that the bubble shrinks and disappears, reducing the area of embolism^4,19,20,21. A previous study suggested that the time of brain gas clearance was significantly shorter with 100% inhaled oxygen than with inhaled air¹⁷.

There were no significant differences in the duration of embolization or the HR, MAP and PetCO₂ at the time of the most severe embolization among the three groups. This may be due to the limited number of cases of severe GE in all three groups. In addition, the number of bubbles in the heart cavity is not necessarily proportional to clinical manifestations. According to the statistical results, when the inhaled oxygen concentrations were 30%, 50% and 100%, the cases of grade V image were 1, 2 and 2, respectively, but this did not indicate that the higher the inhaled oxygen concentration was, the more severe of the GE. The two cases of grade V image with 100% inhaled oxygen concentration may have been caused by the large amount of intravasation and the abundance of blood vessels at the resection site, which resulted in excessive gas entry with fluid from multiple damaged vessels.

Compared with previous studies focusing on the influence of the surgical operation on GE, our study used clinical observation to focus on ventilation during anesthesia, which is innovative. Furthermore, we did not find relevant reports on the effect of inhaled oxygen concentration on GE during hysteroscopic surgery.

However, there are also some limitations of this study. Due to the discontinuity of TTE images, GE of higher grades may be underestimated. In addition, due to the need for surgery, each patient had different intrauterine pressures, and the amount of intravasation could not be controlled. However, there was no significant difference between the three groups. Given the low incidence of severe GE in the three groups, whether 100% oxygen concentration can reduce the severity of GE needs to be further tested.

Oxygen concentration is an independent risk factor for the occurrence of GE. In hysteroscopic surgery, a higher oxygen concentration inhaled by patients could reduce the incidence of GE, indicating that a higher inhaled oxygen concentration, especially 100%, could be recommended for patients during hysteroscopic surgery. However, whether 100% oxygen can reduce the severity of GE needs to be further tested.

GE Gas embolism

ASA American Society of Anesthesiologists

ECG Electrocardiogram

SPO₂ Saturation of Pulse Oxygen

PetCO₂ End-tidal carbon dioxide partial pressure

TTE Transthoracic echocardiography

MAP Mean arterial blood pressure

HR Heart rate

Authors’ contributions

XD, HL and XM L designed the study. XD, JS Z and MD collected the data. XD analyzed the data and drafted the manuscript and was further modified by HL. HL and XM L contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

The study was approved by the Chinese Ethics Committee of Registering Clinical Trials (Chairperson Taixiang Wu, Reference number: ChiECRCT20210033) on 12 February 2021.

All patients provided signed informed consent before admission.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Acknowledgements

Not applicable.

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No competing interests reported.

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Effects of different fractions of inspired oxygen on gas embolization during hysteroscopic surgery: A double-blind randomized controlled trial

Status:

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Abstract

Figures

Background

Methods

Data collection

Sample size calculation

Statistical analyses

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1