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Upper gastrointestinal motility disorders are common during anesthesia induction and are closely related to reflux aspiration; however, there is a lack of research on gastroesophageal reflux during anesthesia induction. In this study, we applied high-resolution impedance measurement (HRIM) to characterize gastroesophageal reflux during anesthesia induction.
Methods
A total of 28 patients participated in this study, with 14 patients receiving anesthesia induction with propofol and succinylcholine, and 14 patients receiving anesthesia induction with propofol and rocuronium. A HRIM catheter was used to collect esophageal impedance and pressure data throughout the anesthesia induction process.
Results
Prior to anesthesia induction, none of the 28 patients experienced gastroesophageal reflux. Within 10 min of anesthesia induction, 12 patients experienced gastroesophageal reflux (n = 12/28; 42.9%). A total of 16 reflux events occurred, all of which remained in the esophagus and did not enter the pharyngeal cavity. Within 5 min after anesthesia induction, 5 patients in the succinylcholine group experienced reflux (n = 5/14; 35.7%), with a statistically significant difference compared to before induction (95% confidence interval, CI 0.435–0.950, P = 0.02). While 4 patients in the rocuronium group experienced reflux (n = 4/14; 28.6%) within 5 min after anesthesia induction, with a statistically significant difference compared to before induction (95% CI 0.513–0.995, P = 0.049), there was no statistically significant difference between the two groups (95% CI 0.539–1.502, P = 0.500). Compared to baseline values, there was no significant decrease in barrier pressure (BrP) in both groups of patients during anesthesia induction. All 16 instances of gastroesophageal reflux during anesthesia induction were related to transient lower esophageal sphincter relaxation (TLESR).
Conclusion
Up to 42.9% of patients experienced reflux within 10 min of anesthesia induction, with the majority occurring within 5 min. The gastroesophageal reflux during anesthesia induction was related to TLESR, not to a decrease in gastroesophageal BrP.
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Introduction
Aspiration pneumonitis is major complication associated with anesthetic management and can seriously threaten the safety of patients [1]. The lower esophageal sphincter (LES) is the main physiological barrier to regurgitation of gastric contents [2]. The maintenance of esophageal tension is complex, involving neural regulation and mechanical input [3].
Many drugs used during anesthesia can affect esophageal tension [4, 5] and a decrease in esophageal tension can increase the likelihood of reflux. Previous studies have evaluated the incidence of gastroesophageal reflux during anesthesia using pH probes, with the incidence ranging from 4.8% to 22.2%. It is noteworthy that these studies had varying observation durations and were not confined to the period of anesthesia induction [6‐8]. Esophageal pH monitoring can effectively identify acid reflux events in gastroesophageal reflux by detecting changes in pH values within the esophagus, but increasing evidence suggests that esophageal pH probes underestimate the frequency of reflux events as they are insensitive to non-acidic reflux [9, 10]. In a 24‑h observation of healthy volunteers, it was found that only 54.9% of gastroesophageal reflux was acidic [11].
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The high-resolution impedance measurement method (HRIM) used in this study is different from traditional detection techniques, as impedance detects all reflux regardless of acidity and defines the direction of flow. In the article “Modern Diagnosis of Gastroesophageal Reflux Disease: Lyon Consensus”, it is explicitly stated that a 24‑h reflux event count greater than 80 is pathological reflux and serves as the diagnostic basis for gastroesophageal reflux disease [12]. Intraluminal impedance monitoring is considered the only recording method that can achieve high-sensitivity detection of all types of reflux events [13]. The HRIM method measures esophageal pressure through 423 sensors distributed longitudinally and radially along the esophagus, while monitoring esophageal impedance (36 sensors). It uses impedance technology and does not rely on acidity detection to determine the occurrence of gastroesophageal reflux. It can provide a very detailed assessment of esophageal pressure and reflux, identifying anomalies that were not detected by traditional detection methods [14]. Therefore, this study used HRIM to monitor the occurrence of gastroesophageal reflux in patients in whom anesthesia was induced with propofol, succinylcholine and rocuronium.
Methods
The study was conducted in the Anesthesiology Department of the China-Japan Friendship Hospital in Beijing, China, and written informed consent was acquired from each patient. This study was approved by the Ethics Committee of the China-Japan Friendship Hospital (2015–33) and registered on ClinicalTrials.gov (NCT:05556408).
Patients
This study included 28 patients aged between 28 and 59 years old with American Society of Anesthesiologists (ASA) classification system II data. Patients with diabetes, pharyngeal diseases, digestive system diseases, current pregnancy or lactation, and body mass index (BMI) greater than 30 kg/m2 were excluded. All patients underwent preoperative preparation according to routine clinical practice and did not receive any preoperative drugs. They were randomly assigned to either the succinylcholine group or the rocuronium group.
High-resolution impedance manometry
Manometry and impedance data were recorded using a 4.2 mm diameter catheter housing 36 circumferential pressure sensors that were spaced 1 cm apart and 36 cm long impedance segments (Sierra Scientific Instruments, Los Angeles, CA, USA) (Fig. 1). After standard calibration in accordance with the manufacturer’s specifications, catheters were placed transnasally. The catheter can continuously monitor the impedance and pressure from the pharynx to the stomach (Fig. 2).
Fig. 1
Manometry catheter housing 36 circumferential pressure sensors that were spaced 1 cm apart and 36 cm long impedance segments
ManoView recording. Impedance and pressure were recorded from the pharynx to the stomach. Time was shown on the X‑axis, and location was shown on the Y‑axis. Red represented high pressure, and blue represented low pressure
Before catheterization, the patients were monitored through electrocardiogram, pulse oximetry, automatic noninvasive arterial blood pressure, bispectral index (BIS) measurements, and an intravenous cannula was inserted. The manometric catheter was inserted through the nose until the pressure from the hypopharynx to the stomach could be recorded. After confirming the position of the catheter, tape was used to fix the catheter to the nose. Patients in the rocuronium group received train of four (TOF) muscle relaxation monitoring.
After stabilizing for 3 min, the patients were given 100% oxygen through a mask for 5 min. Subsequently, the patients received a bolus dose of 2 mg/kg propofol. After the patients became apneic and the BIS was below 60, the patient received face mask ventilation using pressure controlled ventilation, with a peak inspiratory pressure of 15 cmH2O, a respiratory rate of 10 breaths per minute and an inspiratory expiratory ratio of 1:2. Muscle relaxants were administered, with the rocuronium group receiving 1 mg/kg rocuronium and the succinylcholine group receiving 1.5 mg/kg succinylcholine. After the TOF of the rocuronium group reached 0, the visible muscle tremors in the succinylcholine group disappeared, endotracheal intubation was performed through a Macintosh direct laryngoscope. The pressure of the tracheal intubation cuff is 20–30 cmH2O.
After intubation, positive pressure ventilation with volume control was performed, with a tidal volume of 6–8 ml/kg of ideal body weight, with 50% oxygen concentration, and the ventilation was adjusted to maintain an end-tidal carbon dioxide value of 37–42 mm Hg. Anesthesia was maintained by pumping propofol (4–12 mg/kg/h) and BIS values were kept to between 40–60. The pressure was measured for a total of 10 min after anesthesia induction, and then the pressure-measuring catheter was removed. The study ended before the surgery began. Patients remained in a supine position throughout the entire process.
Manometric and impedance data were continuously recorded and displayed as real-time topographical plots (Fig. 2). For subsequent evaluation, each intervention was marked on the horizontal axis.
Data analysis
Manoview® analysis software (Sierra Scientific Instruments, Inc.) was used for data analysis. The software’s thermal compensation function was used for all data. On the contour plots, the esophageal sphincter could be located by sudden changes in pressure (Fig. 2). The proximal edge of the LES was defined by a sudden transition to intraesophageal pressure, while the distal edge was defined by a sudden transition to intragastric pressure. The intragastric pressure was measured 2 cm below the LES. The barrier pressure (BrP) was defined as the difference between the LES pressure and intragastric pressure. Liquid bolus entry was the time at which a 50% fall in impedance from the baseline defining the liquid reflux was reached. Transient lower esophageal sphincter relaxation (TLESR) was defined as the sustained relaxation of LES for more than 10 s without swallowing [15]. All data was recorded in the Excel® table (Microsoft Corporation, Redmond, Washington, USA) and using StatView® (Abacus Concepts, Inc., Berkeley, California, USA) analysis.
Statistical analysis
All data were coded and recorded into SPSS 17.0 software. Categorical data were described as singular data points, and continuous data as mean ± SD. Categorical data were compared using Fisher’s exact test, while continuous data were compared using Student’s t-test. Differences were considered statistically significant at p < 0.05.
Results
All 28 patients completed the study. Table 1 shows the demographic data.
Table 1
Demographic data of the patients included in the two groups in the study
Sex
Age (years)
Height (cm)
Weight (kg)
BMI (kg/m2)
Succinylcholine group, n = 14 Mean ± SD
7 women
46.86 ± 8.76
165.36 ± 9.60
65.21 ± 14.39
23.60 ± 3.13
Rocuronium group, n = 14 Mean ± SD
7 women
48.50 ± 7.97
162.00 ± 6.37
63.54 ± 9.85
24.17 ± 3.11
SD standard deviation, BMI body mass index
During the anesthesia induction in 28 patients, a total of 12 patients experienced gastroesophageal reflux (n = 12/28; 42.9%). Among the 12 patients who experienced reflux, 9 experienced 1 episode of reflux, 2 experienced 2 episodes of reflux, and 1 experienced 3 episodes of reflux, for a total of 16 reflux events. All reflux remained in the esophagus and did not enter the pharyngeal cavity.
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Among the 28 patients, no reflux occurred within 5 min before administering anesthesia inducing drugs. Within 5 min after anesthesia induction, 5 patients in the succinylcholine group experienced reflux (n = 5/14; 35.7%), with a statistically significant difference compared to before induction (95% confidence interval, CI 0.435–0.950, P = 0.02), 5 patients experienced 8 episodes of gastroesophageal reflux, 4 patients in the rocuronium group experienced reflux (n = 4/14; 28.6%) within 5 min after anesthesia induction, with a statistically significant difference compared to before induction (95% CI 0.513–0.995, P = 0.049) and 4 patients experienced 4 episodes of gastroesophageal reflux. There was no statistically significant difference between the two groups (95% CI 0.539–1.502, P = 0.500). After 5 min of anesthesia induction until the end of the study, during mechanical ventilation, 2 patients in each group experienced reflux once (n = 2/14; 14.3%), with no statistically significant difference compared to before induction (95% CI 0.692–1.062, P = 0.241) (Table 2).
Table 2
The occurrence of reflux in two muscle relaxant drug groups
Group(times)
T0
T1
T2
T3
Total
Succinylcholine group, n = 14
0
4
4
2
10
Rocuronium group, n = 14
0
3
1
2
6
Total
0
7
5
4
16
Before anesthesia induction (T0), after propofol administration to before muscle relaxant administration (T1), after muscle relaxant administration to 5 min after induction (T2), and during the mechanical ventilation period (T3) from 5–10 min after anesthesia induction
After administering propofol before muscle relaxant administration, 6 patients (n = 6/28; 21.4%) experienced 7 episodes of gastroesophageal reflux, including 2 male patients (n = 2/14; 14.3%) and 4 female patients (n = 4/14; 28.6%). There was no statistically significant difference in the incidence of reflux between genders after administering propofol (95% CI 0.361–15.942, P = 0.324). There was no statistically significant difference in age between patients with reflux after propofol administration and those without reflux (95% CI −6.007 to 9.855, P = 0.622).
Further analysis was conducted on the barrier pressure during inspiration in all patients during anesthesia induction (Table 3).
Table 3
The barrier pressure during inspiration in two muscle relaxant drug groups
T0
T1
T2
T3
Succinylcholine group, n = 14 (mm Hg)
26.12 ± 7.34
31.34 ± 6.88
22.79 ± 4.46
29.30 ± 6.60
(P = 0.006, 95% CI
(P = 0.095, 95% CI
(P = 0.094, 95% CI
−8.63861 to −1.78711)
−0.65978 to 7.32692)
−6.97219 to 0.62219)
Rocuronium group, n = 14 (mm Hg)
22.21 ± 8.86
27.96 ± 4.75
24.25 ± 4.64
22.65 ± 4.44
(P = 0.005, 95% CI
(P = 0.330, 95% CI
(P = 0.840, 95% CI
−9.40056 to −2.09087)
−6.38581 to 2.31153)
−4.99245 to 4.12245)
Before anesthesia induction (T0), after propofol administration to before muscle relaxant administration (T1), after muscle relaxant administration to 5 min after induction (T2), and during the mechanical ventilation period (T3) from 5–10 min after anesthesia induction. The P-value was compared with T0 in the same group. In the succinylcholine group T2 compared to T1 P = 0.000 (95% CI 4.909–12.184), T3 compared to T2 P = 0.003 (95% CI −10.317 to −2.700). In the rocuronium group T2 compared to T1 P = 0.000 (95% CI 2.020–5.400), T3 compared to T2 P = 0.073 (95% CI −0.173 to 3.377)
Among the 28 patients, within 5 min before anesthesia induction, 1 patient in each group (n = 1/14; 7.1%) experienced TLESR once but no reflux occurred. Within 5 min after anesthesia induction, 7 patients in the succinylcholine group had TLESR episodes (n = 7/14; 50.0%), showing a statistically significant difference compared to before induction (95% CI 1.078–3.198, P = 0.016). These 7 patients experienced 10 TLESR episodes. In the rocuronium group, 4 patients had TLESR episodes within 5 min after anesthesia induction (n = 4/14; 28.6%), with no statistically significant difference compared to before induction (95% CI 0.905–1.867, P = 0.163). These 4 patients had 4 TLESR episodes. There was no statistically significant difference between the two groups (95% CI 0.377–1.301, P = 0.220). After 5 min of anesthesia induction until the end of the study, during mechanical ventilation 2 patients in each group had TLESR episode (n = 2/14; 14.3%), showing no statistically significant difference compared to before induction (95% CI 0.837–1.403, P = 0.500).
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Within 10 min after anesthesia induction, a total of 14 out of 28 patients (n = 14/28; 50.0%) experienced 19 TLESRs episodes, of which 16 episodes (n = 16/19; 84.2%) were accompanied by gastroesophageal reflux. The 16 reflux events that occurred during anesthesia induction were all related to TLESRs (Table 4).
Table 4
The occurrence of TLESRs in two muscle relaxant drug groups
Group (times)
T0
T1
T2
T3
Total
Succinylcholine group, n = 14
1
4
6
3
14
Rocuronium group, n = 14
1
3
1
2
7
Total
2
7
7
5
21
Before anesthesia induction (T0), after propofol administration to before muscle relaxant administration (T1), after muscle relaxant administration to 5 min after induction (T2), and during the mechanical ventilation period (T3) from 5–10 min after anesthesia induction
Aspiration of gastric contents is a major complication related to anesthesia management. In a study conducted in the UK it was found that in reports of anesthesia -elated airway difficulties (n = 133), it was the second most common airway complication, second only to difficult intubation. Aspiration was the most common primary cause of death in anesthesia events (primary event in 50% of deaths) [16]. The results of the fourth UK National Audit Project (NAP4) indicated that lung aspiration accounted for 50% of reported deaths among the main complications of airway management and was the most common cause of anesthesia-related deaths [16]. Aspiration of gastric contents accounted for 5% claims in the American Society of Anesthesiologists Closed Claims Project, with 57% of cases of lung aspiration resulting in death [17].
Due to the lack of stable esophageal tracheal isolation, regurgitation during anesthesia induction was most likely to cause aspiration [1]. Many drugs used during anesthesia induction may affect esophageal tone and motility, increasing the likelihood of gastric contents reflux [4, 5, 18].
In a retrospective study by Sun et al. it was found that the incidence of reflux during anesthesia induction was 0.015% in 166,491 patients; however, in this study the observation of gastric contents in the oral, pharyngeal and laryngeal cavities was defined as reflux. This evaluation method seriously underestimated the proportion of gastric contents reflux and the impact of anesthesia induction drugs on upper gastrointestinal motility as many tiny refluxes were difficult to identify and many reflux events remained in the esophagus without entering the pharyngeal cavity [1]. Some studies also used pH probes to monitor gastroesophageal reflux but this underestimated the frequency of gastroesophageal reflux because it was insensitive to non-acidic reflux [6‐8].
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This is the first study to use HRIM to characterize esophageal reflux during anesthesia induction. Propofol and succinylcholine, propofol and rocuronium are the most commonly used rapid sequential induction drug combinations [19]. Up to 42.9% of patients experienced reflux within 10 min of anesthesia induction, with the majority occurring within 5 min of anesthesia induction; however, all reflux remained in the esophagus and did not enter the pharyngeal cavity and no aspiration occurred. All reflux remained in the esophagus, which was related to the fact that all patients in this study followed preoperative fasting guidelines and had lower gastric contents. Therefore, considering that nearly half of the patients in this study experienced reflux during anesthesia induction, if a full stomach patient is encountered, aspiration is highly likely to occur during anesthesia induction. Therefore, it is very important to follow preoperative fasting guidelines and to use ultrasound to evaluate the volume of gastric contents before surgery.
Of the patients 21.4% experienced reflux after receiving propofol before muscle relaxant administration, indicating that deep sedation with propofol can lead to reflux. The use of propofol for deep sedation is a common anesthetic method in clinical practice, such as anesthesia for painless gastrointestinal endoscopy. At this time, attention should be paid to the possibility of reflux aspiration, and suction devices should be prepared.
The choice between rocuronium and succinylcholine for rapid sequential induction has always been a controversial issue, as it was previously believed that muscle twitching after succinylcholine administration may lead to increased gastric pressure, further causing gastric content reflux and aspiration in patients [20]; however, there is currently no comparative study on the reflux situation during anesthesia induction using succinylcholine and rocuronium separately. In our study, there was no statistically significant difference in the proportion of patients who experienced gastroesophageal reflux and TLESRs within 5 min after anesthesia induction using succinylcholine and rocuronium.
Traditional beliefs hold that the pressure difference between the esophagus and the gastric cavity was the most important factor in preventing gastroesophageal reflux [21, 22]; however, our data suggest that maintaining barrier pressure may not be a necessary condition for preventing reflux during anesthesia induction because in this study we found that the patient’s barrier pressure did not decrease during anesthesia induction and even increased after administration of propofol. During anesthesia induction, we found that all reflux was related to TLESRs, rather than a decrease in barrier pressure. Up to 84.2% of TLESRs were accompanied by gastroesophageal reflux. In the study by He et al. 24‑h HRIM monitoring of 15 healthy volunteers showed that 81.8% of TLESR was related to reflux [23]. In a study targeting mechanically ventilated critically ill patients, it was found that 68% of the occurrence of gastroesophageal reflux was caused by TLESRs [24] and TLESRs also play a critical role in the occurrence of gastroesophageal reflux disease [21].
The occurrence of TLESR may be a normal physiological movement. In a 24‑h monitoring of healthy subjects, TLESRs mainly occur during eating (12.2 times/h) and within 2 h after meals (7 times/h), while the incidence is significantly reduced in a supine fasting state (1.8 times/h) [23]. In the succinylcholine group, the probability of TLESRs occurring within 5 min after anesthesia induction was significantly increased compared to 5 min before anesthesia induction, indicating that the increase in TLESRs and related reflux after anesthesia induction was related to anesthesia induction rather than physiological events.
This study has several limitations. Firstly, although this study is only an exploratory physiological study, the small sample size may hinder the generalizability of the results due to selection bias. In response to the specific scenario of gastroesophageal reflux during anesthesia induction that this study focuses on, our research design focuses more on capturing all potential reflux events (regardless of acidity) and changes in barrier pressure to assess the risk of perioperative reflux aspiration, rather than analyzing the acidity of the refluxed material. Physiological changes under anesthesia may cause acidic or non-acidic reflux, and even non-acidic reflux can pose a significant risk of aspiration pneumonia to anesthetized patients. Therefore, in the impedance pH joint monitoring catheter and pressure impedance joint monitoring catheter, we chose the pressure impedance joint monitoring catheter; however, in future research, we plan to include a impedance pH joint monitoring catheter to synchronously record impedance changes and pH fluctuations and conduct in-depth analysis of the clinical associations between different types of reflux events, in order to further improve the evaluation system for perioperative gastroesophageal reflux.
This study indicates that HRIM monitoring is safe and feasible in anesthesia-induced patients. The use of HRIM can help clarify the situation of gastroesophageal reflux during anesthesia induction, and has great potential in improving our understanding of the impact of anesthesia on upper gastrointestinal motility in patients, paving the way for more effective and safer treatment options; however, more research is needed to better understand the clinical significance of our findings.
Conclusion
Up to 42.9% of patients experienced reflux within 10 min of anesthesia induction, with the majority of reflux occurring within 5 min of anesthesia induction. Gastroesophageal reflux during anesthesia induction is associated with TLESRs, rather than a decrease in gastroesophageal barrier pressure.
Funding
This work was supported by a grant from the Foreign Expert Services Department of the Ministry of Science and Technology of China (No. G2022065007L).
Declarations
Conflict of interest
Y. Cao, W. Wang, S. Zhao and Y. Zhang declare that they have no competing interests.
This study was approved by the Ethics Committee of the China-Japan Friendship Hospital (2015–33). Written informed consent was acquired from each patient.
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