Population Pharmacokinetics of Remifentanil in Low-Weight Critically Ill Patients

• 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.
• 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.
• 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.

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