Population Pharmacokinetics of Remifentanil in Low-Weight Critically Ill Patients

Fudan University

Status: Enrolling

Conditions: Critical Illness; Pain

Treatments: Drug: Remifentanil

Study type: Observational

Funder types: Other

Identifiers

NCT07301970

2025-007-01K

Details and patient eligibility

About

The goal of this prospective clinical study is to learn about the population pharmacokinetics (PopPK), safety, and efficacy of remifentanil in low-body-weight patients in the Intensive Care Unit (ICU) who require mechanical ventilation. The main questions it aims to answer are:

1. What are the pharmacokinetic characteristics of remifentanil in low-weight ICU patients?
2. How does remifentanil (and concurrent propofol use) affect hemodynamic stability (such as blood pressure) and sedation efficacy in this population?

Participants receiving mechanical ventilation will receive remifentanil for analgesia and sedation according to a standardized protocol. They will undergo arterial blood sampling at specific time points to measure drug concentrations. Researchers will also record hemodynamic parameters. Additionally, a subset of patients receiving propofol as a rescue sedative will have plasma propofol concentrations measured to evaluate its influence on blood pressure changes.

Full description

1. Background: Remifentanil is a lipophilic μ-opioid receptor agonist characterized by rapid onset and offset, making it ideal for analgosedation in the Intensive Care Unit (ICU). Body weight is a significant factor affecting its pharmacokinetics (PK). Low-body-weight patients may require different dosing strategies. This study aims to establish a population pharmacokinetic (PopPK) model for remifentanil in mechanically ventilated patients with low body weight and to evaluate its safety and efficacy, with a specific focus on hemodynamic stability.

2. Study Protocol & Dosing Strategy: This is a single-center, prospective observational study designed to reflect real-world clinical practice. Eligible patients requiring invasive mechanical ventilation will receive remifentanil for analgesia and sedation.

   • Co-administration: In accordance with standard ICU practice, remifentanil is often administered concurrently with propofol to ensure adequate sedation and analgesia.
   • Dosing Regimen: The administration of a loading dose is discretionary based on the patient's clinical condition; in many cases, a continuous infusion is initiated directly without a loading dose to maintain hemodynamic stability.
   • Infusion Rate: The continuous infusion is typically initiated at a standardized clinical rate (e.g., approximately 0.18 mg/h) or a weight-based equivalent.
   • Titration: Subsequent dosing is titrated dynamically based on clinical response (e.g., patient comfort, ventilator synchrony) and hemodynamic tolerance.

3. Pharmacokinetic Sampling (Sparse & Opportunistic): Blood samples are not collected at rigid clock times but are distributed to capture key PK phases:

   • Absorption/Distribution Phase: Samples collected within the first hour of infusion (e.g., 1-2 samples).
   • Steady State: Samples collected during stable continuous infusion.
   • Elimination Phase: Samples collected immediately prior to stopping the infusion and at multiple intervals after discontinuation.

5.Hemodynamic Assessment & Propofol Co-variate Analysis: Hemodynamic parameters (MAP, HR) are continuously monitored. Given that propofol is co-administered in most patients and significantly impacts hemodynamics, plasma propofol concentrations will be measured in a subset of patients. These data will be incorporated into the PopPK/PD analysis as a covariate to distinguish the hemodynamic effects of remifentanil from those of propofol.

Enrollment: 45 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age: ≥18 years old, regardless of sex;
• Normal weight: 18.5 kg/m² ≤ Body Mass Index (BMI) < 24 kg/m² or Low weight: BMI < 18.5 kg/m²;
• Admitted to the intensive care unit (ICU);
• Required invasive mechanical ventilation for more than 10 hours;
• The subject or their legal guardian has fully understood the potential risks and benefits of participating in this study and has signed the informed consent form.

Exclusion criteria

• Pregnant women;
• Presence of severe respiratory impairment or respiratory depression during the screening period;
• Known hypersensitivity to remifentanil or any of the excipients;
• Meeting other contraindications for opioid use

Trial design

45 participants in 2 patient groups

Low-weight group

Description:

BMI \< 18.5

Treatment:

Drug: Remifentanil

Normal-weight group

Description:

18.5 ≤ BMI\< 24

Treatment:

Drug: Remifentanil