Population Pharmacokinetics of Remifentanil in Low-Weight Critically Ill Patients

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.

• Mean Arterial Pressure (MAP) [Срок оценки: From baseline throughout the duration of drug infusion (up to approximately 48 hours).]
• Plasma Concentration of Propofol [Срок оценки: From the start of its administration, through the maintenance infusion phase, up to 2 hours after the end of infusion.]
• Heart Rate [Срок оценки: From baseline throughout the duration of drug infusion (up to approximately 48 hours).]