Pharmacokinetics of Sufentanil After Epidural Administration

Pharmacokinetics of Sufentanil After Epidural Administration in Patients Undergoing Abdominal Surgery

Sufentanil is an opioid analgesics used in all groups of patients. It has one of the strongest effects among analgesic drugs. Sufentanil is widely-used because of its very quick onset, short duration of action, and better hemodynamic stability in patients compared to other opioids. Most of the pharmacokinetic studies described intravenous administration of sufentanil. The drug can also be epidural administrated (especially continuous epidural infusion) in low concentration with local anesthetics (ropivacaine or bupivacaine) for epidural analgesia. Epidural analgesia offers effective pain relief not only during the surgery, but also postoperatively. The combination of two drugs provides their additive effect and can reduce doses required for pain relief, then decreases the number and severity of adverse events. The study aims to describe the pharmacokinetics of epidural sufentanil used perioperative in adult patients after abdominal surgery to adjust the dosage if necessary.

Study Overview

• Status: Completed
• Conditions: Epidural Analgesia; Abdominal Surgery; Epidural; Anesthesia
• Intervention / Treatment: Drug: Epidural administration of sufentanil

Detailed Description

The patients qualified for abdominal surgery were enrolled in the study. All patients were premedicated with oral midazolam (7.5 mg). Epidural cannulations were placed by anesthesiologists before general anesthesia. The catheters' placement procedure was conducted under local anesthesia and according to the local protocol for the infections' prevention. The epidural infusion (solution of 0.2 % ropivacaine 5 ml with 25 to 50 mcg sufentanil in 50 ml of 0,9% NaCl) was started with a 5 mL bolus of the mentioned solution a few minutes before skin incision. The continuous infusion was maintained throughout the surgery at the rate of 3-12 mL/h. The patients were induced into general endotracheal anesthesia according to a standardized protocol, with propofol 1-3 mg/kg, fentanyl 1-2 mcg/kg, and rocuronium bromide 0.6 mg/kg. Anaesthesia was continued by using sevoflurane or desflurane MAC 1 to maintain mean arterial pressure with a value of +/- 20% of the original value. The postoperatively patients were monitored in the PACU (Post Anesthesia Care Unit) for 1 hour and then transferred to the intensive care unit or surgical unit according to their clinical status and co-morbidities. Whole blood samples (2.0 ml) were collected to measure sufentanil concentrations - during the epidural infusion and up to 72 hours after its cessation. Vital parameters (e.g. blood pressure, saturation, heart rate, respiratory rate, and pain score) were monitored at regular intervals. The epidural sufentanil and ropivacaine infusion were continued after surgery as long as was necessary.

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• Poland
  • Greater Poland
    • Poznań, Greater Poland, Poland, 60-355
      • Heliodor Swiecicki Clinical Hospital in Poznan
  • Pomeranian Voivodeship
    • Gdańsk, Pomeranian Voivodeship, Poland, 80-416
      • Medical University of Gdansk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The adult patients qualified to abdominal surgery performed in epidural anesthesia using sufentanil.

Description

Inclusion Criteria:

• age 18-70 years,
• qualifications for abdominal surgery,
• ASA I-III

Exclusion Criteria:

• proven allergies to sufentanil,
• lack of written confirmed consent of a patient

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adult patients received epidural sufentanil during and after abdominal surgery; All patients were premedicated with oral midazolam 7,5 mg and then they were induced into general endotracheal anesthesia according to a standardized protocol, with propofol 1-3 mg/kg, fentanyl 1-2 ug/kg and rocuronium bromide 0.6 mg/kg. Anaesthesia was continued with sevoflurane or desflurane MAC 1 to maintain mean arterial pressure with a value of +/- 20% of the original value. The epidural sufentanil infusion was started with bolus during anesthesia and continued after surgery as long as was necessary.

Drug: Epidural administration of sufentanil; The epidural cannulations were placed by anesthesiologists before general anesthesia. Correct positioning of the catheters were tested and confirmed by negative aspiration and injection of 3 mL of 2% Lidocaine. The epidural infusion (solution of 0.2 % ropivacaine 5 ml with 25 to 50 mcg sufentanil in 50 ml of 0,9% NaCl) was started with bolus of 5 ml over 5 minutes and then continuous infusion was maintained was throughout the surgery at 3-12 mL/h and 2-12 mL/h after the surgery. Single dose of sufentanil was given when needed.; Other Names: Continuous epidural infusion of sufentanil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the depth of analgesia using NRS	Measurement of the depth of analgesia using NRS (Numeral Rating Scale) during epidural administration of sufentanil. Sufentanil was given for surgery patients during and after abdominal surgery as an analgesic agent.	before the beginning of sufentanil administration, during sufentatnil administration, up to 72 hours after sufentatnil administration
Sufentanil plasma concentrations [pg/ml]	Measurements of sufentanil plasma concentrations [pg/ml] during epidural analgesia with sufentanil. Whole blood samples (2.0 ml) were collected according to the study protocol.	5, 30 minutes, 1, 2, 4, 6, 12 h after the begining of epidural infusion of sufentanil, then 1 blood samples every 24 h, just before the epidural infusion cessation and 3, 5, 20, 40 minutes, and 1, 2, 6, 12, 36, 72 hours after the infusion cessati
Systolic blood pressure	Measurements of systolic blood pressure during epidural analgesia with sufentanil.	before the beginning of sufentanil administration, during sufentatnil administration, up to 72 hours after the cessation of sufentatnil administration
Diastolic blood pressure	Measurements of diastolic blood pressure during epidural analgesia with sufentanil.	before the beginning of sufentanil administration, during sufentatnil administration, up to 72 hours after the cessation of sufentatnil administration
Heart rate	Measurements of heart rate during epidural analgesia with sufentanil.	before the beginning of sufentanil administration, during sufentatnil administration, up to 72 hours after the cessation of sufentatnil administration

Collaborators and Investigators

• Sponsor: Poznan University of Medical Sciences
• Collaborators: Medical University of Gdansk; Clinical Hospital Heliodor Swiecicki of the Medical University of Karol Marcinkowski in Poznań
• Investigators: Study Director: Edmund Grześkowiak, MSc, PhD, Poznan University of Medical Sciences; Study Director: Krzysztof Kusza, MD, PhD, Heliodor Swiecicki Clinical Hospital in Poznan

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): February 28, 2020
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: October 1, 2023
• First Submitted That Met QC Criteria: October 1, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 1, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: pharmacokinetics; sufentanil; epidural analgesia; abdominal surgery; epidural anesthesia; surgery patients
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Sufentanil; Dsuvia
• Other Study ID Numbers: 1144/18; 2014/15/N/NZ7/03028 (Other Grant/Funding Number: Polish National Science Centre)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data with analysis will be available after a publication of study results as a manuscript.
• IPD Sharing Time Frame: The data will be available in 12 months and available for 5 years
• IPD Sharing Access Criteria: Scientists
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No