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) in consecutive 4-hour windows from 0-4 through 44-48 hours after the end of anesthesia. Concentrations are estimated from intraoperative and postoperative IV-PCA fentanyl dosing histories using the Shafer pharmacokinetic model. Assessment ends at IV-PCA termination or 48 hours after the end of anesthesia, whichever occurs first. If IV-PCA ends within a window, the minimum concentration from the start of that window to termination is used; subsequent windows are excluded. The concentration at the end of anesthesia is reported descriptively and excluded from the mixed-effects models because it is an instantaneous value rather than an interval minimum. Trajectories are compared between 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 90 patients (gastric resection, n=17; colorectal resection, n=73), modeled fentanyl Ce_min during IV-PCA up to 48 h after the end of anesthesia was higher after gastric resection (primary no-interaction model: difference, 0.121 ng/mL; 95% CI, 0.047-0.194; p=0.0016). The group-by-time interaction was not significant (p=0.0829). Adjusted and sensitivity analyses yielded similar results. No significant differences in pain or adverse events were detected; some assessments were missing.

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 for each outcome.

PONV was assessed at anesthesiologists' routine postoperative ward rounds at approximately 10:00 a.m. on weekdays. Assessments were unavailable when postoperative day 1 or 2 fell on weekends or holidays.
Postoperative day 1 nausea and vomiting: 16/54 (29.6%), 0/11 (0%).
Postoperative day 2 nausea and vomiting: 6/34 (17.6%), 1/6 (16.7%).

Previously registered pruritus results are retained:
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 hours after the end of anesthesia: 4/73 (5.5%), 1/17 (5.9%).
Respiratory depression was defined as any documented respiratory rate <10 breaths/min or SpO2 <90% within this period, with no minimum duration criterion. Respiratory depression data were available for all 90 patients. PONV 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 conventional laparoscopic and robot-assisted procedures.

The primary outcome was the trajectory of interval-specific minimum modeled fentanyl effect-site concentration (Ce_min) in consecutive 4-hour windows from 0-4 through 44-48 hours after the end of anesthesia. Assessment ended at IV-PCA termination or 48 hours after the end of anesthesia, whichever occurred first. If IV-PCA ended within a window, the minimum concentration from the start of that window to termination was used; subsequent windows were excluded. The concentration at the end of anesthesia was reported descriptively and excluded from the mixed-effects models because it was an instantaneous value rather than an interval minimum. The group-by-time interaction was not statistically significant (p=0.0829). In the primary linear mixed-effects model without the interaction term, Ce_min was 0.121 ng/mL higher in the MIGR group than in the MICR group (95% CI, 0.047-0.194; p=0.0016).

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 detected 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 hours: 8/73, 3/17.
PCA demands within 24 hours: 4 [2-8], 7 [4-12].
PCA bolus deliveries within 24 hours: 4 [1-7], 6 [4-9].
Intentional IV-PCA discontinuation within 48 hours: 11/73, 1/17.
Cumulative fentanyl dose delivered via IV-PCA within 48 hours: 1200 [1067-1324], 1300 [991-1500] ug.

PCA demand and delivery data over 24 hours were available for 70 MICR and 16 MIGR patients. Three MICR patients and one MIGR patient whose IV-PCA ended before 24 hours were treated as having missing data for these measures. Cumulative fentanyl dose data within 48 hours were available for all 90 patients (MICR, n=73; MIGR, n=17).

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 single-center retrospective observational study at Tokushima University Hospital uses existing electronic health records and Amy infusion pump records from patients who received postoperative intravenous fentanyl during routine care. Data include patient characteristics, surgical procedures, medications, fentanyl dosing histories, pain assessments, and adverse events. Fentanyl effect-site concentrations are estimated from dosing histories using a pharmacokinetic model to examine differences by surgical procedure and associations with pain and adverse events. No research-directed treatment or additional tests are performed. Patients who opt out or lack dosing records 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 pump. This registration covers a gastric versus colorectal resection analysis of a subset of the approved study population: 90 patients who underwent surgery between October 2021 and February 2024.

After registration, Ce_min assessment windows were standardized to consecutive 4-hour intervals from 0-4 through 44-48 hours after the end of anesthesia. The concentration at the end of anesthesia was excluded from the mixed-effects models and reported descriptively because it is an instantaneous value rather than an interval minimum. The main results reflect the updated analysis. The statistical analysis plan was developed after data access. Postoperative nausea and vomiting (PONV) assessment was restricted to anesthesiologists' postoperative ward rounds; the previous compilation also included ward records. Event counts and numbers of patients with available PONV assessments were updated accordingly. Cumulative fentanyl dose delivered via IV-PCA within 48 hours after the end of anesthesia was updated using data from all 90 patients.

Registered date

2026

Year

09

Month

16

Day

Last modified on

2026

Year

10

Month

27

Day

Link to view the page

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