Compare the Effects of Remifentanil and Fentanyl on the Duration of Mechanical Ventilation of ICU Patients

Compare the Effects of Remifentanil and Fentanyl on the Duration of Mechanical Ventilation of ICU Patients: a Multi-centre, Randomized, Controlled Trial

To verify whether remifentanil is more beneficial to reduce the duration of mechanical ventilation, shorten the interval from SBT to extubation, reduce the incidence of adverse events, reduce the workload of nursing staff, reduce the dosage of sedatives and ICU hospitalization costs, shorten the length of ICU hospitalization, and reduce the short-term mortality.

Opioids are widely used for analgesia in the ICU, of which, fentanyl and remifentanil are the most commonly used. Compared with the two analgesics, fentanyl is relatively cheap, but it is metabolised by liver. Long-term infusion makes its half-life extended, and side effects increase significantly. Respiratory depression is the most serious side effect and may lead to re-intubation and even sudden death.

Remifentanil is a strong selective μ-opioid receptor agonist, rapidly metabolized by non-specific plasma and tissue esterases into inactive metabolites; it has very short context-sensitive half-life even after prolonged infusion or in patients with organ failure. Remifentanil is easy to titrate and provides excellent analgesia: it allows higher doses administration than are normally used with traditional opioids without concerns about accumulation or delayed recovery.

This feature is helpful for patients with mechanical ventilation to weaning and extubate early. Previous studies comparing the two drugs mainly focus on short-term postoperative application, and theoretically long-term use can better reflect the pharmacokinetic advantages of Remifentanil. So we designed this study.

Inclusion Criteria:

• (1) Oral endotracheal intubation requiring mechanical ventilation; and (2) 18-85 years old; and (3) expected to require mechanical ventilation for longer than 24 hours.

Exclusion Criteria:

• (1) Deep sedation is required (PaO2/FiO2 ≤100, loss of consciousness during treatment with muscle relaxants, status epilepticus, surgery or surgical conditions require absolute immobilization, severe brain injury with intracranial hypertension, therapeutic hypothermia, etc. And other clinical assessments need to maintain RASS<-2); (2) The time of using sedatives or opioid analgesics is longer than 1 week before enrollment; (3) ICU stay ≥ 1 week before enrollment; (4) Invasive mechanical ventilation time ≥ 48 hours before enrollment; (5) According to the condition of the disease, it is estimated that mechanical ventilation will be needed for too long, such as the accumulation of respiratory muscles in peripheral neuromuscular diseases, brainstem damage and respiratory center involvement; (6) Delirium, alcohol withdrawal symptoms or mental illness or use of antipsychotic drugs; (7) Severe abnormal liver function (Child-Pugh grade C); (8) Renal insufficiency requires renal replacement therapy; (9) Surgical treatment is required during mechanical ventilation (except for minor operations, such as lumbar puncture, ventricular drainage, etc.); (10) Allergy to study drugs or other contraindications; (11) Pregnant or lactating women; (12) Has been selected for other RCT tests; (13) The patient or the legally authorized person is unwilling to participate in the trial; (14) The investigator judged that the patient was not suitable for selection (such as severe hypotension; potential disputes, etc.)