Effect of inhibition of pain axis conduction on maternal gastric emptying during labor: a prospective controlled study

doi:10.21203/rs.3.rs-5338203/v1

Background:

The pain during labor is severe, and epidural analgesia is often used to inhibit pain axis conduction at present. Diet management during labor is very important during the whole process of labor. Therefore, we compared gastric emptying of semi-solid food between parturient women undergoing versus not undergoing epidural analgesia.

Methods

Seventy full-term, low-risk parturients were selected and divided into two groups according to epidural analgesia status: epidural analgesia group (LA, n= 35) and non-epidural analgesia group (NA, n= 35). The cross-sectional area of the gastric antrum (CSA₀) was measured while fasting using B-ultrasound, and the time recorded as T0. The parturients in both groups then ate about 300 g millet congee (about 600 KJ). The CSAs of the gastric antra were measured by ultrasonography 60, 90, and 120 minutes after the experimental meal, these areas being recorded as CSA₁, CSA₂ and CSA₃ and the corresponding time points as T1, T2, and T3. Pain scores of parturients at these four time points were recorded. Gastric emptying time was also recorded.

Results

CSA₁, CSA₂, and CSA₃ were larger in the NA than in the LA group, and the gastric emptying time was longer in the NA than in the LA group (P<0.05). Pain scores were higher in the NA than LA group at the three time points of T1, T2, T3 (P<0.05).

Conclusions

Inhibition of the pain axis conduction by epidural analgesia can promote gastric emptying during labor. Therefore, semisolid food intake during vaginal delivery does not increase the risk of vomiting and aspiration in women undergoing labor analgesia compared with women without labor analgesia.

Pain axis conduction

Ultrasound

Labor analgesia

Gastric emptying

Parturients often experience severe pain during labor. Epidural analgesia can inhibit the conduction of pain axis, and is applied in more than 80% of our hospital. The process of delivery consumes a huge amount of energy, which may result in ketosis if the parturients eat nothing during a long process of delivery. ^[1-2]However, because women in labor are at high risk of vomiting and aspiration, diet management during labor has been controversial. Clinical guidelines of the Royal College of Obstetricians and Gynecologists of the Canadian Association of Obstetriciansrecommend that low-risk parturients take light diets

. ^[3-4]Studies have shown that gastric emptying is weaker in parturient than in non-parturient women. ^[5]However, there are few clinical studies on changes in gastric emptying in parturients undergoing epidural labor analgesia versus those who do not. Therefore, this study was designed to compare the changes in gastric emptying, as determined by ultrasound, between women who did and did not undergo epidural analgesia during the same period to provide a reference for clinical application. we hypothesized that the emptying capacity of the stomach changes between the in parturients undergoing epidural labor analgesia versus those who do not.

General information

This study was approved by the Ethics Committee of our college ([2022] 42) and the participants gave their written informed consent before labor. The inclusion criteria comprised: pregnant women with full-term singleton intending to give birth naturally, age 18 to 35 years, ≥37 weeks pregnant, body mass index (BMI) 19 to 35 kg/m², ASA grade Ⅱ, cervical dilatation 1 to 2 cm, no intake of solids for at least 6 hours, no intake of clear liquids for at least 1 hour. The exclusion criteria comprised severe complications of pregnancy, not fasting in accordance with the above criteria, in labor for less than 2 hours, poor effect of labor analgesia (VAS pain score>5 after 20 minutes of labor analgesia),the pregnant women with induced labor, history of upper gastrointestinal surgery, multiple pregnancies, obesity (BMI≥ 35 kg/m² before pregnancy,) and comorbidities (diabetes or gestational diabetes, hypothyroidism, chronic opioid intake) that have a potential impact on gastric emptying.

Procedures

The parturient should provide her written informed consent before labor if they pemit to join the study. When the cervix of the parturient was evaluated by the midwife as 1–2 cm dilated , if the parturient chose epidural analgesia, she joined the epidural analgesia group (LA group), otherwise she joined the non-epidural analgesia group(NA group). The epidural technique was the continuous infusion , and the epidural procedure for achieving painless delivery was as follows: the L2–L3 or L2–L3 epidural space was punctured and the catheter was placed approximately 4-5cm cephalad in the epidural space; no blood or outflow was drawn back. Next, 3 mL 1% lidocaine was injected to determine the position of the catheter in the epidural space and connect the program-controlled pulse analgesia pump. The drug formulation was 0.08% ropivacaine + sufentanil (0.4 ug/mL) to a total of 100 mL, the first dose being 6–15 mL, followed by continuous infusion at 1 mL/h, pulse input 9.9ml at one hour interval, self-controlled administration 9.9 mL, locking time 15 mins, limit 35 mL/h. there was no anaesthetic drug applied in the epidural space or intravenous injection in NA group.

The maternal CSA was recorded as CSA₀ as soon as a parturient was enrolled in either group. In the LA group, provided the vital signs were stable and there was no other discomfort within 10 mins after achieving labor analgesia, the parturient was asked to eat approximately 300 g of millet congee (approximately 600 KJ). Parturients in the NA group were also asked to eat approximately 300 gram of millet congee (approximately 600 KJ) 10 minutes after joining the group. The gastric antrum was examined by ultrasonography 60, 90, and 120 mins after the experimental meal. These CSAs of the antrum were recorded as CSA₁, CSA₂, and CSA₃, respectively_. After that, ultrasonography of the gastric antrum was repeated every 5min, when no liquid or solid contents were seen in the antrum and the CSA of the antrum was less than 381mm² [7-8], It was defined as gastric emptying, We stopped the ultrasonography at this point. Maternal CSAs were measured under B-ultrasound as follows: with the parturient in a semirecumbent position, the superior mesenteric artery, aorta, and left lobe of the liver under the xiphoid process were identified and an antral section made. The CSA of the gastric antrum was calculated as follows: CSA = (AP×CC×π)/4 (AP: anteroposterior diameter; CC: craniocaudal diameter). ^[6-7]Each measurement was repeated three times and the average calculated . The most important point is that the ultrasound image is recorded by the anesthesiologist. After removing the individual grouping information of the ultrasound image, the professional ultrasound doctor performs the image analysis and records the results.

Clinical observations

The following basic participant characteristics were recorded: age, BMI, pregnancy-related data (including gestational weeks), CSA₀,CSA₁, CSA₂, CSA₃, time of gastric emptying, and pain scores at the four time points when ultrasound was performed. The incidence of nausea and vomiting was also recorded.

Statistical analysis

The data were analyzed using SPSS22.0 statistical software. Normally distributed data are expressed as mean ±standard deviation (x̄±s). One-way ANOVA was used for inter-group comparisons, and a repeated measurement design ANOVA was used for intra-group comparisons. Numerical data are expressed as number (%) and the Fishers exact probability test was used for comparison between groups. P < 0.05 was considered to denote statistical significance.

This study was a randomized controlled trial, the experimental group was LA, the control group was NA, and the research subject was gastric emptying time. According to the literature and preliminary experiment results, the gastric emptying time of the control group was 220.9±29min, and the gastric emptying time of the LA group was about 25min shorter than that of the NA group. A two-sided alpha of 0.05 was set at 90% power , the calculated sample size was 29 cases in each group. According to the dropout rate of 20% in each group, 35 cases were finally included in each group.

There were no significant differences in age, weight, gestational age between the two groups (P>0.05) (Table 1)

Table 1. Basic participant characteristics according to study group

Group

N

Age(years)

BMI(kg/m2)

Gestational weeks

First-time parity n (%)

LA

35

27.9+3.5

26.5+2.6

39.1+1.0

64%

NA

p

t

35

28.1+3.1

0.89

0.13

26.3+2.9

0.77

0.33

39.2+1.2

0.58

0.46

58%

Values are mean±SD or actual numbers , BMI=Body Mass Index .

Categorical are presented as number (%)

P < 0.05 considered as significant

Gastric antrum areas and gastric emptying were assessed at the specified times and compared between the two groups.

Table 2 shows CSA₀ in the basal state and CSA₁, CSA₂ and CSA₃ at 60, 90, and 120 mins after the experimental meal for both groups. There was no significant difference in CSA₀ between the two groups whereas CSA₁, CSA₂, and CSA₃were all significantly larger in the NA than in the LA group (all P<0.05). Additionally, gastric emptying time was significantly shorter in the LA than in the NA group (P<0.05) (Table 2).

Table 2. Comparison of gastric antrum areas and time to gastric emptying between the two groups

Group

N

CSA₀

(cm^２)

CSA₁

(cm^２)

CSA₂

(cm^２)

CSA₃

(cm^２)

The time of gastric emptying (min)

LA

35

3.7+0.3

10.2+0.6

8.3.+0.5

6.5+0.4

197.5+27.2

NA

p

t

35

3.7+0.3

0.24

1.08

11.4+0.8^ａ

0.00

13.83

9.3+0.6^ａ

0.00

13.56

7.4+0.5^ａ

0.00

11.15

220.9+29.2^ａ

0.00

3.56

Values are mean±SD, between the Preterm group and Atterm group

CSA₁ :P < 0.05

CSA₂:P < 0.05

CSA₃ :P < 0.05

The time of gastric emptying (min):P < 0.05；P < 0.05 considered as significant

Pain scores, total duration of labor, and incidence of nausea and vomiting were compared between the two groups at specified time points

There was no significant difference in pain scores between the two groups at T0. Pain scores were significant lower in the LA than the NA group at the three time points of T1, T2, and T3 (P<0.05)(the corresponding time points of 60, 90, and 120 minutes after the experimental meal were recorded as T1, T2, and T3). The total duration of labor was longer in the LA (519.6+123.9 mins) than in the NA group (459.7+117.6 mins) (P>0.05), The difference between the two groups was not significant. The incidence of nausea and vomiting did not differ significantly between the study groups (Table 3).

Table 3. Comparison of pain scores, total duration of labor, and incidence of nausea and vomiting between the two groups at specified time points

Group	N	T0	T1	T2	T3	Total duration of labor(min)	Incidence of nausea and vomiting (%)
LA	35	6.2+1.2	3.0+0.6	3.5+0.8	3.7+0.8	519.6+123.9	37.1
NA	35	6.3+1.1	6.9+1.1^ａ	7.3+1.2^ａ	7.4+1.2^ａ	459.7+117.6^ａ	31.4
p		0.76	0.00	0.00	0.00	0.06
t		0.30	18.76	18.45	16.69	1.95

Values are mean±SD, between the Preterm group and Atterm group:

T1 ：P < 0.05

T2 ：P < 0.05

T3 ：P < 0.05

Total duration of labor(min): P >0.05；P < 0.05 considered as significant

Many studies have shown that ultrasonic measurement of gastric emptying time has high accuracy and repeatability and is an ideal means to study gastric emptying in pregnant women. In this study, ultrasound was used to conduct a standardized study of parturients who received epidural analgesia and those who did not. We found that under the same conditions, the time to gastric emptying was shorter with epidural analgesia compared with those without epidural analgesia.

Feeding problems during labor analgesia were studied using paracetamol and it was finally confirmed that there was no delay in emptying of the stomach in pregnant women undergoing labor analgesia compared to women who did not use labor analgesia. Bouvet et al. also showed similar gastric emptying in pregnant women who received 125 g yoghurt after epidural analgesia compared to women who did not receive epidural analgesia. Both of these studies have some limitations. Because water and yogurt are easier to empty in the stomach, it is difficult to distinguish, and women need more energy to meet their needs throughout the delivery process.

Some studies have found that the incidence of gastroesophageal reflux and vomiting in patients with gastrointestinal dysfunction after eating semisolid food is lower than that after eating liquid food.^.[9-10]The practice of consuming semi-solid food during labor has been a longstanding tradition in Chinese food culture. ^[11] Chewing and stimulation of chyme can promote gastrointestinal peristalsis ,relieve anxiety and discomfort caused by hunger, and reduce excitement of the sympathetic nervous system. ^[12] With the application of intraspinal anesthesia in critically ill parturients and the support of various advanced technologies for maternal airway management, the incidence of maternal reflux aspiration has been greatly reduced. The resultant extremely low incidence of aspiration means we can pay attention to the energy needs of pregnant women during labor. Therefore, in this study, we chose to investigate whether there is a difference in gastric emptying after eating semi-solid food millet porridge between parturients who received epidural labor analgesia and those who did not. The results showed that under the same conditions, after eating the same amount of semi-solid food such as millet porridge, the gastric emptying time of parturients who received labor analgesia was significantly shorter than that of parturients who did not receive labor analgesia.

Changes in maternal hormone levels, increased uterine compression, uterine contraction pain during labor, breath-holding during labor, and the use of oxytocin and other drugs can all delay gastric emptying and reduce gastrointestinal motility, resulting in retention of gastric contents and increased risk of vomiting and aspiration. The extreme pain associated with uterine contractions during labor is one of the main factors affecting gastric emptying.

The potential mechanisms through which pain influences gastric emptying may encompass the following: 1. hypothalamic-pituitary-adrenal (HPA) axis plays a role in the dysfunction of bidirectional communication between the brain and the gut. Pain can activate the HPA axis and cause the release of adrenocorticotropic hormone releasing factor. Ultimately leads to functional gastrointestinal disorders.^[13] At the same time, when pain, an injury-inducing stimulus, is transmitted to the brain through nerve fibers, functional denervation occurs in the brain, and the intestinal tract increases dopamine activity to stimulate dopamine receptors, thereby inhibiting the release of enteric acetylcholine, ^[13] and the contraction of gastric anulus muscles is subsequently inhibited. In addition, when pain occurs, the autonomic nervous system and pain become inadapted to each other, and sympathetic nerve excitation can cause gastric mucosal blood vessels to contract, causing gastric mucosa ischemia and hypoxia, resulting in weakened gastric motility. ^[14]The end result can delay gastric emptying.

2. Corticotropin releasing factor (CRF) is a neuropeptide related to stress and has an effect on the gastrointestinal tract, and is an important mediator of the middle axis stress response. Pain stress can alter the central stress circuit, leading to increased CR F synthesis. In recent years, studies have shown that CRF 2 receptor 2 (CRF-R2) is related to stress induced gastric emptying inhibition . ^[15]It has been found that central CRF-induced inhibition of gastric emptying is mediated through the sympathetic pathway.

3. The gut is physiologically responsive to emotional and stressful stimuli, and stress and negative emotions can have adverse effects on the gastrointestinal tract. Abnormal psychological states, especially anxiety and depression, can cause disturbances of gastric electrical rhythm by affecting autonomic nerves, thereby affecting gastric emptying.

Nowadays, epidural analgesia was being the most widely used modality. Epidural labor analgesia is achieved by injecting a mixture of local anesthetics and opioids into the lumbar epidural space, relieving the pain caused by uterine contraction and cervical and perineal dilatation by blocking the T10–L1 and S2–S4 nerve roots. In this study, pain scores of parturients were significantly lower in the LA than in the NA group, confirming that epidural analgesia significantly reduces the subjective experience of pain during labor. However, previous clinical studies have shown opioids have adverse effects such as nausea, vomiting, and decreased gastric motility. We therefore believe that epidural analgesia has two opposing effects on postprandial gastric emptying. On

the one hand, relief of acute pain reduces the inhibition of gastric emptying caused by pain; whereas, on the other hand, epidural opioid infusion reduces gastric motility and thus delays gastric emptying.^[16-18] It is not clear which factor is dominant, so the overall effect of epidural labor analgesia on postprandial gastric emptying is not clear.

The following is a summary of our findings. We found that under the same conditions, the antral CSA was smaller and the gastric emptying time was shorter after 60, 90, and 120 minutes of millet porridge in the parturients who received epidural analgesia compared with those who did not. Although the average time difference of gastric emptying is only 23 minutes, we can still observe the promoting effect of labor analgesia on gastric emptying. We think that the reasons for this result may be the following two aspects: On the one hand, the combination of local anesthetics and opioids in epidural analgesia blocks the nerve conduction of pain. In general, opioids have strong lipophilic properties and high affinity for opioid receptors, thus achieving strong analgesic effects, and pain relief alleviates the inhibitory effect of gastric emptying. On the other hand, because epidural labor analgesia uses only small doses of opioids, Therefore, the impact of epidural analgesia on gastric emptying during labor analgesia primarily manifests as a reduction in the inhibition of gastric emptying caused by severe pain, rather than being attributed to the direct effect of opioids on gastrointestinal motility. Consequently, this results in an accelerated rate of gastric emptying.

This study had some shortcomings: First .the pain of uterine contractions during labor may have prevented some parturients from cooperating quietly with the testing and measurement of the CSA of the gastric antrum, making some ultrasonic measurement data inaccurate. Second, the experimental grouping was not based on random method, but on maternal will, so the experimental results may have some limitations.

Therefore, after the analysis of the results of this study, we believe that the gastric emptying of puerpera undergoing epidural analgesia during vaginal delivery is faster than that of patients without epidural analgesia, and puerpera do not need to worry about the eating problem after labor analgesia.

LA: epidural analgesia; NA: non-epidural analgesia; CSA: The cross-sectional area of the gastric antrum; BMI: body mass index ; HPA: hypothalamic pituitary adrenal;CRF: Corticotropin releasing factor ; CRF-R2: CRF 2 receptor 2;

Acknowledgements

We sincerely thank all our research participants who contributed time and effort to this research..

Authors’ contributions

Data curation:Wenhao Bu, Wei Wu.

Formal analysis: Jing Cheng.

Investigation: Wei Wu.

Supervision: Wenhao Bu.

Visualization: Wenhao Bu.

Writing – original draft: Jing Cheng, Wei Wu.

Writing – review & editing: Wenhao Bu.

This study was supported by The Funding for Scientific Research Projects from Wuhan Municipal Health Commission(S202401100071；WX23Z43).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Availability of data and materials

The datasets used and analyzed during the current study are available from

the corresponding author on reasonable request

Ethics approval and consent to participate

All the methods used in the study are in line with the relevant guidelines and regulations and have been carried out in accordance with the Helsinki Declaration. The study protocol was approved by the Research Ethics Committee of Maternal and Child Health Hospital of Hubei Province ([2022] 42) . All participants gave written informed consent.

Consent for publication

Not Applicable

Competing interests

The authors declare that they have no competing interests.

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No competing interests reported.

Effect of inhibition of pain axis conduction on maternal gastric emptying during labor: a prospective controlled study

Status:

Version 1

Abstract

Introduction

Methods

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1