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Original Article Comparison of bispectral index-guided endoscopic ultrasonography with continuous vs. intermittent infusion of propofol: a retrospective study in Japan
Ayana Okamotoorcid, Ken Kamata,orcid, Tomohiro Yamazakiorcid, Shunsuke Omotoorcid, Kosuke Minagaorcid, Mamoru Takenakaorcid, Masatoshi Kudoorcid
Clinical Endoscopy 2024;57(6):814-820.
DOI: https://doi.org/10.5946/ce.2024.019
Published online: July 24, 2024

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan

Correspondence: Ken Kamata Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama 589-8511, Japan E-mail: ky11@leto.eonet.ne.jp
• Received: January 14, 2024   • Revised: March 14, 2024   • Accepted: March 15, 2024

© 2024 Korean Society of Gastrointestinal Endoscopy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background/Aims
    This study aimed to evaluate the safety and efficacy of continuous propofol infusion for anesthesia during endoscopic ultrasonography (EUS).
  • Methods
    A total of 427 consecutive patients who underwent EUS between May 2018 and February 2019 were enrolled in this study. The patients were divided into two propofol infusion groups: continuous (n=207) and intermittent (n=220). The following parameters were compared: (1) propofol dose, (2) respiratory and circulatory depression, (3) body movement requiring discontinuation of the examination, (4) awakening score, and (5) patient satisfaction.
  • Results
    The median total maintenance dose of propofol was significantly higher in the continuous group than in the intermittent group (160.0 mg vs. 130.0 mg, respectively); however, the reduction in SpO2 was significantly lower in the continuous group (2.9% vs. 13.2%). Body movements occurred less frequently in the continuous group than in the intermittent group (40.1% vs. 49.5%, respectively). The rate of complete awakening was significantly higher in the continuous group than in the intermittent group. Finally, there was a significant difference in the percentage of patients who answered “absolutely yes” when asked about receiving EUS again: 52.7% in the continuous group vs. 34.3% in the intermittent group.
  • Conclusions
    Continuous infusion resulted in stable sedation and reduced propofol-associated risks.
  • Keywords: Bispectral; Continuous; Endosonography; Propofol; Sedation
Propofol-induced sedation allows smooth post-procedural awakening; therefore, it is used in patients undergoing endoscopic ultrasonography (EUS) for biliary and pancreatic diseases.1-4 The bispectral index (BIS) monitors the processes and displays electroencephalographic data to assess the effects of general anesthesia during surgery.5,6 In a previous study, we used a BIS monitor to ensure the safe use of propofol during EUS examinations and found that it was useful for maintaining a constant depth of anesthesia while simultaneously reducing the required dose of propofol and body movement during the procedure.7 In particular, the reduction in heart rate (HR) was minimized in patients aged 75 years. According to the Japanese drug packaging insert, the maintenance of propofol-induced anesthesia is facilitated by continuous infusion via a syringe pump. This procedure is intended to maintain general anesthesia during surgery or sedation during ventilation. However, it is unclear whether continuous infusion is appropriate during the EUS examination because of the relatively short average examination time (less than 30 minutes). Indeed, in a previous study, we used an intermittent infusion method (i.e., bolus administration upon detection of body movement or evidence of an elevated BIS value).7 In the present study, we used the continuous infusion method to stabilize sedation and decrease propofol-associated risks such as respiratory or circulatory depression. In addition, we evaluated the safety and efficacy of this anesthesia method during the EUS examination by comparing it with the intermittent infusion method.
Study design
This was a single-center comparative retrospective study using prospectively collected data.
Patients
This study enrolled 427 consecutive patients who underwent EUS for extra- or intra-gastrointestinal tract lesions between May 2018 and February 2019. Regarding propofol-induced sedation, the intermittent infusion method was used during the first half of the study period (intermittent infusion group), and the continuous infusion method was used for the second half (continuous infusion group). Patients were excluded if they met any of the following criteria: age <20 years; American Society of Anesthesiologists physical status score ≥5; allergy to propofol; cranial nerve diseases; pregnancy; hypoxia, with <90% arterial oxygen saturation on pulse oximetry (SpO2); systolic blood pressure (sBP) <90 mmHg; or HR <50 beats per minute (bpm).
Maintenance of propofol-induced anesthesia with a BIS monitor during EUS
A biological information monitor that provided BIS values was attached to all patients, and HR and SpO2 were continuously monitored during EUS. Blood pressure was measured at 5-minute intervals. Three physicians participated in each EUS examination: one performed the EUS, one operated the ultrasound equipment, and one monitored the vital signs/BIS signals and administered propofol. The physician who administered propofol during EUS was instructed by the anesthesiologists and was authorized to use propofol in the hospital. EUS using an echoendoscope (GF-UCT260; Olympus Medical Systems Co. Ltd.) was performed by experienced endosonographers, each of whom had performed more than 1000 EUS procedures. All procedures were performed using an echoendoscope (GF-UCT260). The patient was administered oxygen at a rate of 2 L/min during the examination. Propofol (0.5 mg/kg) was administered to initiate sedation. The initial sedation used only propofol; however, midazolam or pentazocine hydrochloride was used in combination with propofol when anesthesia induction by propofol alone was unsuccessful. Additional doses of propofol (20 mg increments) were administered until adequate induction of anesthesia was achieved. The BIS values were maintained in the range of 60 to 80 during the examination. To achieve this, patients in the continuous and intermittent infusion groups received a 20 mg bolus of propofol if body movement, a rapid increase in the BIS values, or a BIS value >80 was detected. For the initial sedation, the continuous infusion group received propofol at a rate of 4 mg/kg/h via a syringe pump started at the initial sedation. When patients in the continuous group received a bolus (owing to the detection of movement or an increase in the BIS value), the dosing speed was also increased by 1 mg/kg/h (Fig. 1).
Outcome measures
The following parameters related to the EUS examination were compared between the two groups: (1) dose of propofol, (2) respiratory and circulatory depression, (3) occurrence of body movement requiring discontinuation of the examination, (4) awakening score at the time of leaving the endoscopy room and 2 hours after leaving the endoscopy room, and (5) patient satisfaction. Respiratory depression was defined as SpO2 <90%. Circulatory depression was defined as sBP <90 mmHg and/or HR <50 bpm. As previously described, the awakening score was calculated based on the following parameters: motor activity, respiration, sBP, level of consciousness, and SpO2.7 A score of 10 indicates complete awakening. A patient satisfaction survey was conducted among 182 outpatients who underwent EUS, and scoring was based on a Likert scale.8 In the present study, the five-point scale was used to assess the pain level, the patient’s ability to sleep, and their consent for further EUS examinations.
Statistical analysis
Continuous variables were expressed as the mean±standard deviation or as the median and range. Categorical variables were expressed as percentages. Continuous and categorical variables were analyzed using t-tests and chi-square tests, respectively. All analyses were performed using the Bell Curve for Excel (Social Survey Research Information Co., Ltd.). Statistical significance was set at p<0.05.
Ethical statements
The study protocol was approved by the Ethics Committee of Kindai University Faculty of Medicine (approval number: 31-007). Informed consent was obtained from all enrolled participants. All methods were performed in accordance with the relevant guidelines and regulations.
Patients
A total of 427 patients were included in this analysis. The median age was 70 (range, 30-88) years, and the male-to-female ratio was 214:213. Of the 427 patients, 207 and 220 were assigned to the continuous and intermittent infusion groups, respectively. There were no significant differences between the two groups with respect to the median age, male-to-female ratio, median body weight, or median examination time (Table 1). One patient in the continuous group and two patients in the intermittent group required midazolam combined with propofol for anesthesia induction, whereas 16 and 14 patients in the continuous and intermittent groups, respectively, required pentazocine hydrochloride in combination with propofol.
Sedation status during EUS examination
Table 2 compares the sedation status of the intermittent and continuous infusion groups. The median total maintenance dose of propofol (i.e., the median total propofol dose excluding the anesthesia induction dose) was significantly higher in the continuous infusion group than in the intermittent infusion group. Similarly, there was a significant difference in the dose per hour (mg/h) between the groups, but not in the dose per body weight per hour (mg/kg/h). Regarding respiratory and circulatory depression, the reduction in SpO2 was significantly lower in the continuous infusion group than in the intermittent infusion group (2.9% vs. 13.2%, respectively; p=0.003). There were no significant differences in the reductions in sBP or HR. Although the difference between the two groups with respect to body movements was not significant, the occurrence of body movements that required discontinuation of the examination tended to be lower in the continuous infusion group than in the intermittent infusion group (40.1% vs. 49.5%, respectively; p=0.052). The rate of complete awakening was significantly higher in the continuous infusion group than in the intermittent infusion group both at the time of leaving the endoscopy room (2.4% vs. 0%, respectively; p=0.026) and 2 hours after leaving the endoscopy room (96.1% vs. 83.6%, respectively; p=0.003). The awakening scores at 2 hours after leaving the endoscopy room were ≥8, indicating that all patients in both groups were allowed to get out of bed and move around before returning home. The average BIS value during the examination was significantly higher for the continuous infusion group than for the intermittent infusion group (71.2±10.0 vs. 65.7±9.3, respectively; p<0.001), although it is important to note that only the BIS values collected every 5 minutes during the examination were used for the calculation.
Patient satisfaction survey
Of the 427 patients, 180 underwent EUS as outpatients and completed the patient satisfaction survey (Table 3). The percentage of patients who reported “not painful at all” was 87.3% (96/110) in the continuous infusion group and 88.6% (62/70) in the intermittent infusion group; however, the difference was not significant (p=1.000). The percentage of patients who reported “slept very well” was 90.0% (99/110) in the continuous infusion group and 88.6% (62/70) in the intermittent infusion group; however, the difference was not statistically significant (p=0.806). The percentage of patients who reported “absolutely yes” when asked about undergoing EUS in the future was 52.7% (58/110) in the continuous infusion group and 34.3% (24/70) in the intermittent infusion group; this difference was statistically significant (p=0.021).
Benzodiazepines, such as midazolam, can provide optimal sedation during upper endoscopy examinations.9 A systematic review comparing midazolam with propofol found no significant differences in patient satisfaction, retest request rate, test memory loss rate, or respiratory and cardiovascular depression. However, the recovery time from sedation was significantly shorter after propofol.10 Propofol also has the advantage of providing stable sedation for heavy drinkers who may have difficulty in achieving sedation because of the de-suppression caused by benzodiazepines. There is no consensus regarding the type of sedation used for upper endoscopy, and little is known about the optimal sedation method for EUS examinations. Our hospital uses propofol for sedation during EUS examinations.7 In the present study, we compared continuous and intermittent infusions of propofol during BIS monitor-guided EUS, and found that continuous infusion was beneficial for respiratory suppression, early arousal, and retest request rates.
As shown in Table 2, there was a significant difference between the two groups in the median total maintenance dose of propofol. However, the significance disappeared when body weight was considered, suggesting that differences in body weight affected the total dose required. The average BIS value was significantly higher in the continuous infusion group, suggesting that the patients maintained a stable blood concentration of propofol to achieve a BIS value of 60 to 80 without being excessively sedated. This may have helped prevent a decrease in SpO2 and body movement, as well as early awakening from sedation. The significantly higher number of patients in the continuous group who consented to a further EUS examination may be due to early awakening from sedation and most likely also due to memory loss (the patient was unlikely to wake during the examination) (Fig. 1); however, we did not assess memory loss in the present study.
A previous randomized trial, similar to our study, compared continuous and intermittent infusion of propofol.11 The differences from our study in terms of methodology include the use of endoscopic retrograde cholangio-pancreaticography (ERCP) as well as EUS (ERCP, n=60; EUS, n=40), use of target-controlled infusion (TCI), and no use of BIS. Data from the randomized trial showed that the mean procedure time and total propofol dose exceeded 30 minutes and 300 mg, respectively. Therefore, the duration was significantly longer, and the propofol dose was higher than in our study.11 This may be because more than half of the subjects underwent ERCP. The TCI syringe pump automatically changed the continuous infusion speed of the drug based on the target blood concentration calculated by the software in the pump.12 Note that the blood concentration and brain concentration cannot be measured; what is displayed on the screen is only a simulation generated by the software. In our study, we did not use a TCI pump; rather, we administered propofol according to body weight and used a BIS monitor (electroencephalographic monitor) to maintain an appropriate depth of anesthesia because of the large individual differences in anesthetic requirements for each patient. In a randomized trial, the continuous infusion group had a significantly longer recovery time from anesthesia, and hypotension was more common.11 The authors concluded that this was because of an increase in the total dose of propofol administered via continuous injections. In contrast, in our study, there was no difference in the total dose per body weight per hour between the two groups, and the incidence of respiratory and circulatory depression was higher in the intermittent infusion group. Although it is difficult to make a simple comparison owing to the differences in methodology between the two studies, the use of a BIS monitor may help prevent propofol overdose.
This study has several limitations. First, this was a retrospective study, even though the data were collected prospectively. In addition, we did not record changes in the BIS values over time or the frequency of mid-procedure awakening. Finally, the percentage of patients with memory loss and the precise recovery time from sedation were not recorded.
In conclusion, the present study demonstrated the usefulness of continuous propofol infusion during BIS monitor-guided EUS, particularly with respect to the maintenance of stable anesthesia during a median examination time of approximately 20 minutes. Further studies are required to assess the utility of this method in colonoscopy, endoscopic submucosal dissection, and ERCP, all of which require longer procedure times and are more invasive.
Fig. 1.
Schematic showing assumed propofol levels in the blood of the intermittent and continuous infusion groups. The continuous infusion method is expected to maintain a more stable blood concentration of propofol than the intermittent infusion method, leading to a reduction in bolus frequency.
ce-2024-019f1.jpg
ce-2024-019f2.jpg
Table 1.
Patient characteristics
Characteristic Continuous group (n=207) Intermittent group (n=220) p-valuea)
Median age (range, yr) 69 (30–86) 71 (30–88) 0.094
Male: female (n) 98:109 116:104 0.287
Median body weight (range, kg) 57.9 (30.0–130.0) 56.8 (30.0–140.0) 0.757
Median examination time (range, min) 24.0 (4–97) 22.0 (2–89) 0.926

a)Comparison of the continuous and intermittent groups.

Table 2.
Comparison of sedation status between the intermittent and continuous infusion groups
Continuous group (n=207) Intermittent group (n=220) p-value
Median total maintenance dose of propofol (mg)a) 160.0 (30.0–495.0) 130.0 (20–380.0) <0.001
Median maintenance dose of propofol (mg/h) 414.3 (99.0–960.0) 342.9 (23.4–3,300.0) 0.011
Median maintenance dose of propofol (mg/kg/h) 16.8 (1.0–225.0) 13.8 (0.3–1,650.0) 0.567
Rate of SpO2 drop during EUS 6 (2.9) 29 (13.2) 0.003
Rate of sBP drop during EUS 24 (11.6) 23 (10.5) 0.888
Rate of HR drop during EUS 38 (18.4) 36 (16.4) 0.820
Occurrence of body movementb) 83 (40.1) 109 (49.5) 0.052
Average number of body movementsc) 2.2±1.5 2.5±1.6 0.309
Rate of complete awakening when leaving the endoscopy room 5 (2.4) 0 (0) 0.026
Rate of complete awakening at 2 hours after leaving the endoscopy room 199 (96.1) 184 (83.6) 0.003

Values are presented as median (range), number (%), or mean±standard deviation.

SpO2, arterial oxygen saturation of pulse oximetry; EUS, endoscopic ultrasonography; sBP, systolic blood pressure; HR, heart rate.

a)Total dose, omitting the dose used for initial sedation.

b)Body movement was defined as movement requiring discontinuation of the examination.

c)Average value in cases with body movement.

Table 3.
Results of the patient satisfaction survey
Continuous group (n=110) Intermittent group (n=70)
Did you feel pain?
 Not painful at all 96 62
 Not painful 8 2
 Neither 1 3
 Painful 0 2
 Very painful 5 1
Did you sleep well?
 Slept very well 99 62
 Slept well 8 2
 Neither 1 1
 Not slept well 0 3
 Not slept at all 2 2
Would you like to receive EUS examination next time?
 Absolutely yes 58 24
 Yes 38 37
 Neither 11 5
 No 1 1
 Absolutely no 2 3

EUS, endoscopic ultrasonography.

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  • 2. Lee TH, Lee CK, Park SH, et al. Balanced propofol sedation versus propofol monosedation in therapeutic pancreaticobiliary endoscopic procedures. Dig Dis Sci 2012;57:2113–2121.ArticlePubMedPDF
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        Comparison of bispectral index-guided endoscopic ultrasonography with continuous vs. intermittent infusion of propofol: a retrospective study in Japan
        Clin Endosc. 2024;57(6):814-820.   Published online July 24, 2024
        DOI: https://doi.org/10.5946/ce.2024.019
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      Comparison of bispectral index-guided endoscopic ultrasonography with continuous vs. intermittent infusion of propofol: a retrospective study in Japan
      Image Image
      Fig. 1. Schematic showing assumed propofol levels in the blood of the intermittent and continuous infusion groups. The continuous infusion method is expected to maintain a more stable blood concentration of propofol than the intermittent infusion method, leading to a reduction in bolus frequency.
      Graphical abstract

      Fig. 1.

      Graphical abstract

      Comparison of bispectral index-guided endoscopic ultrasonography with continuous vs. intermittent infusion of propofol: a retrospective study in Japan
      Characteristic Continuous group (n=207) Intermittent group (n=220) p-valuea)
      Median age (range, yr) 69 (30–86) 71 (30–88) 0.094
      Male: female (n) 98:109 116:104 0.287
      Median body weight (range, kg) 57.9 (30.0–130.0) 56.8 (30.0–140.0) 0.757
      Median examination time (range, min) 24.0 (4–97) 22.0 (2–89) 0.926
      Continuous group (n=207) Intermittent group (n=220) p-value
      Median total maintenance dose of propofol (mg)a) 160.0 (30.0–495.0) 130.0 (20–380.0) <0.001
      Median maintenance dose of propofol (mg/h) 414.3 (99.0–960.0) 342.9 (23.4–3,300.0) 0.011
      Median maintenance dose of propofol (mg/kg/h) 16.8 (1.0–225.0) 13.8 (0.3–1,650.0) 0.567
      Rate of SpO2 drop during EUS 6 (2.9) 29 (13.2) 0.003
      Rate of sBP drop during EUS 24 (11.6) 23 (10.5) 0.888
      Rate of HR drop during EUS 38 (18.4) 36 (16.4) 0.820
      Occurrence of body movementb) 83 (40.1) 109 (49.5) 0.052
      Average number of body movementsc) 2.2±1.5 2.5±1.6 0.309
      Rate of complete awakening when leaving the endoscopy room 5 (2.4) 0 (0) 0.026
      Rate of complete awakening at 2 hours after leaving the endoscopy room 199 (96.1) 184 (83.6) 0.003
      Continuous group (n=110) Intermittent group (n=70)
      Did you feel pain?
       Not painful at all 96 62
       Not painful 8 2
       Neither 1 3
       Painful 0 2
       Very painful 5 1
      Did you sleep well?
       Slept very well 99 62
       Slept well 8 2
       Neither 1 1
       Not slept well 0 3
       Not slept at all 2 2
      Would you like to receive EUS examination next time?
       Absolutely yes 58 24
       Yes 38 37
       Neither 11 5
       No 1 1
       Absolutely no 2 3
      Table 1. Patient characteristics

      Comparison of the continuous and intermittent groups.

      Table 2. Comparison of sedation status between the intermittent and continuous infusion groups

      Values are presented as median (range), number (%), or mean±standard deviation.

      SpO2, arterial oxygen saturation of pulse oximetry; EUS, endoscopic ultrasonography; sBP, systolic blood pressure; HR, heart rate.

      Total dose, omitting the dose used for initial sedation.

      Body movement was defined as movement requiring discontinuation of the examination.

      Average value in cases with body movement.

      Table 3. Results of the patient satisfaction survey

      EUS, endoscopic ultrasonography.

      Table 1.

      Table 2.

      Table 3.

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