UMIN-CTR Clinical Trial

Public title

A study comparing estimated fentanyl concentrations during patient-controlled pain relief after laparoscopic or robot-assisted stomach and colorectal surgery

Acronym

Fentanyl concentrations after stomach and colorectal surgery

Scientific Title

Fentanyl effect-site concentrations required for postoperative analgesia: a retrospective study using records from the Amy infusion pump

Scientific Title:Acronym

Fentanyl effect-site concentrations for postoperative analgesia

Region

Japan

Condition

Postoperative pain following laparoscopic or robot-assisted gastric or colorectal resection

Classification by specialty

Gastrointestinal surgery

Anesthesiology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To retrospectively characterize modeled fentanyl effect-site concentration trajectories during the first 48 hours after the end of anesthesia in adults receiving postoperative fentanyl intravenous patient-controlled analgesia (IV-PCA), and to compare interval-specific minimum modeled effect-site concentrations (Ce_min) between minimally invasive gastric resection and minimally invasive colorectal resection. Both groups include conventional laparoscopic and robot-assisted laparoscopic procedures.

Basic objectives2

Others

Basic objectives -Others

An observational study examining the association between surgical procedure and postoperative fentanyl effect-site concentration trajectories estimated from routine clinical dosing records.

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The trajectory of interval-specific minimum modeled fentanyl effect-site concentration (Ce_min, ng/mL) during the first 48 hours after the end of anesthesia. Effect-site concentrations are estimated from fentanyl dosing histories using the Shafer pharmacokinetic model. The predicted concentration at the end of anesthesia is included as the initial value. Subsequent values are the minimum concentrations within the 0-2-hour and 2-4-hour windows and successive 4-hour windows through 44-48 hours. Assessment ends at IV-PCA termination or 48 hours after the end of anesthesia, whichever occurs first. Trajectories are compared between the gastric and colorectal resection groups.

Key secondary outcomes

1. Pain at rest and during movement on postoperative days 1 and 2, assessed using the numeric rating scale (NRS, 0-10) during weekday postoperative ward rounds at approximately 10:00 a.m.
2. Occurrence of postoperative nausea and vomiting (PONV) and pruritus on postoperative days 1 and 2.
3. Occurrence of respiratory depression within 48 hours after the end of anesthesia, defined as a respiratory rate below 10 breaths/min or oxygen saturation (SpO2) below 90%.
4. Initial IV-PCA settings and subsequent setting adjustments during observation.
5. Numbers of PCA demands and successfully delivered boluses within 24 hours after the end of anesthesia.
6. Intentional IV-PCA discontinuation within 48 hours after the end of anesthesia.
7. Cumulative fentanyl dose delivered via IV-PCA within 48 hours after the end of anesthesia.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

70

years-old

>

Gender

Male and Female

Key inclusion criteria

Patients meeting all of the following criteria:

1. Underwent elective laparoscopic or robot-assisted gastric or colorectal resection under general anesthesia at Tokushima University Hospital between October 2021 and February 2024.
2. Were aged 20 years or older and younger than 70 years at the time of surgery.
3. Received postoperative intravenous patient-controlled analgesia (IV-PCA) with fentanyl.

Key exclusion criteria

Patients meeting any of the following criteria:

1. Conversion to open surgery.
2. Unavailable or incomplete IV-PCA administration records that preclude reconstruction of the dosing history required to estimate fentanyl effect-site concentrations.
3. Refusal to allow the use of their clinical information for this study.

Target sample size

90

Name of lead principal investigator

1st name	Rousuke
Middle name
Last name	Kawanishi

Organization

Tokushima University Hospital

Division name

Surgical Center

Zip code

770-8503

Address

3-18-15 Kuramoto-cho, Tokushima-shi, Tokushima, Japan

TEL

088-633-7181

Email

kawanishi.riyosuke@tokushima-u.ac.jp

Name of contact person

1st name	Yuki
Middle name
Last name	Maeda

Organization

Tokushima University Hospital

Division name

Department of Anesthesiology

Zip code

770-8503

Address

3-18-15 Kuramoto-cho, Tokushima, Japan

TEL

088-633-7181

Homepage URL

Email

maeda.yuuki@tokushima-u.ac.jp

Institute

Tokushima University

Institute

Department

Personal name

Organization

Tokushima University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

JAPAN

Co-sponsor

Name of secondary funder(s)

Organization

Life Science / Medical Research Ethics Review Board of Tokushima University Hospital

Address

2-50-1 Kuramoto-cho, Tokushima, Japan

Tel

088-633-7958

Email

brinshoshienk@tokushima-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2026

Year

09

Month

16

Day

URL releasing protocol

Full protocol not publicly available; opt-out information is published on the hospital website.

Publication of results

Partially published

URL related to results and publications

Presented in part at ANESTHESIOLOGY 2025; a direct results URL has not been identified.

Number of participants that the trial has enrolled

90

Results

In a subgroup analysis of 17 gastric and 73 colorectal resection patients, modeled fentanyl Ce_min over 48 h was higher after gastric resection (estimated difference, 0.145 ng/mL; 95% CI, 0.086-0.204). No statistically significant differences in pain or adverse events were detected. Results were presented in part at ANESTHESIOLOGY 2025.

Results date posted

2026

Year

09

Month

15

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

This gastric versus colorectal resection analysis included 90 patients. MICR denotes minimally invasive colorectal resection and MIGR denotes minimally invasive gastric resection. Both groups included laparoscopic and robot-assisted procedures. Values are medians [interquartile ranges] or counts.

Overall (n=90): age 60 [53-66] years; 38 women; BMI 22.5 [20.7-24.5] kg/m2.
MICR (n=73): age 60 [54-66] years; 32 women; BMI 22.5 [20.8-24.5] kg/m2.
MIGR (n=17): age 53 [49-61] years; 6 women; BMI 21.5 [19.9-24.1] kg/m2.

Participant flow

For the gastric versus colorectal resection analysis, 125 patients who underwent surgery between October 2021 and February 2024 were assessed for eligibility. Thirty-three patients with unavailable postoperative IV-PCA records and two whose procedures were converted to open surgery were excluded. Ninety patients were included in the primary analysis: 73 in the MICR group and 17 in the MIGR group. This was a retrospective observational study without research-directed treatment allocation or randomization.

Adverse events

Results are reported for the 90-patient gastric versus colorectal resection analysis. Values below are presented in the order MICR, then MIGR. Denominators indicate patients with available data.

Postoperative day 1 nausea and vomiting: 16/56 (28.6%), 0/11 (0%).
Postoperative day 2 nausea and vomiting: 10/53 (18.9%), 2/11 (18.2%).
Postoperative day 1 pruritus: 2/50 (4.0%), 0/11 (0%).
Postoperative day 2 pruritus: 0/31 (0%), 0/7 (0%).
Respiratory depression within 48 h after the end of anesthesia: 4/73 (5.5%), 1/17 (5.9%).

Respiratory depression was defined as a respiratory rate below 10 breaths/min or SpO2 below 90%. Nausea, vomiting, and pruritus assessments had missing data; available observations were used. These findings do not establish a causal relationship with fentanyl.

Outcome measures

Results are reported for the 90-patient gastric versus colorectal resection analysis. MICR denotes minimally invasive colorectal resection (73 patients), and MIGR denotes minimally invasive gastric resection (17 patients). Both groups included laparoscopic and robot-assisted procedures.

The primary outcome was the trajectory of interval-specific minimum modeled fentanyl effect-site concentration (Ce_min) over 48 h after the end of anesthesia. At the end of anesthesia, the predicted effect-site concentration at that time point was used. The time-averaged between-group difference estimated using a linear mixed-effects model was 0.145 ng/mL higher in MIGR than in MICR (95% CI, 0.086-0.204; p<0.001).

Secondary pain outcomes were NRS scores (0-10). Values below are medians [interquartile ranges], presented in the order MICR, then MIGR.

Postoperative day 1, at rest: 2 [2-3], 4 [2-5].
Postoperative day 1, during movement: 5 [4-7], 6 [4-7].
Postoperative day 2, at rest: 2 [0-3], 3 [1-4].
Postoperative day 2, during movement: 4 [4-5], 5 [2-7].

No statistically significant between-group differences were found for these pain outcomes. Pain assessments were available for 54 MICR and 11 MIGR patients on postoperative day 1 and for 34 MICR and 6 MIGR patients on postoperative day 2. Results for postoperative nausea and vomiting, pruritus, and respiratory depression are reported in the Adverse events field.

IV-PCA settings and utilization are reported below. Values are medians [interquartile ranges] or numbers of patients with the characteristic/number assessed, presented in the order MICR, then MIGR. The unit ug denotes micrograms. All utilization assessment periods begin at the end of anesthesia.

Initial settings:
Fentanyl concentration in the IV-PCA solution: 13 [12-14], 13 [11-15] ug/mL.
Basal infusion rate: 26 [24-28], 26 [22-30] ug/h.
Dose per PCA bolus: 13 [12-15], 13 [11-15] ug.
Lockout interval of 10 min: 11/73, 6/17; 15 min: 4/73, 0/17; 20 min: 58/73, 11/17.
Droperidol added to the IV-PCA solution: 50/73, 13/17.

Any change in IV-PCA settings within 48 h: 8/73, 3/17.
PCA demands within 24 h: 4 [2-8], 7 [4-12].
PCA bolus deliveries within 24 h: 4 [1-7], 6 [4-9].
Intentional IV-PCA discontinuation within 48 h: 11/73, 1/17.
Cumulative fentanyl dose delivered via IV-PCA within 48 h: 1200 [1057-1300], 1250 [987-1471] ug.

PCA demand and delivery data over 24 h were available for 70 MICR and 16 MIGR patients. Three MICR patients and one MIGR patient whose IV-PCA ended before 24 h were treated as having missing data for these measures. Cumulative fentanyl doses over 48 h were available for 67 MICR and 16 MIGR patients. Six MICR patients and one MIGR patient whose IV-PCA continued beyond 48 h were treated as having missing data for this measure because the dose delivered up to 48 h could not be determined accurately.

Plan to share IPD

There is no plan to share individual participant data outside the institution.

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2024

Year

03

Month

15

Day

Date of IRB

2024

Year

05

Month

27

Day

Anticipated trial start date

2024

Year

03

Month

16

Day

Last follow-up date

2027

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This is a single-center retrospective observational study at Tokushima University Hospital. Patients who received postoperative intravenous fentanyl using the Amy infusion pump as part of routine clinical care are identified from existing electronic medical records and pump administration records. Data collected include patient characteristics, surgical procedures, medications, fentanyl administration histories, pain assessments, and adverse events. Fentanyl effect-site concentrations are estimated from administration histories using a pharmacokinetic model. Differences across surgical procedures and associations with pain and adverse events are examined. No treatment interventions or additional examinations are performed for research purposes. Patients who opt out of the study or whose pump administration records are unavailable are excluded. The overall study population comprises patients who underwent surgery at our hospital between January 2021 and May 2024 and received postoperative pain management using the Amy infusion pump. This registration covers a comparison of gastric and colorectal resection using a subset of patients from the overall approved study. This comparison includes 90 patients who underwent surgery between October 2021 and February 2024.

Registered date

2026

Year

09

Month

16

Day

Last modified on

2026

Year

09

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000072041