The choice of the sedation protocol has a massive impact on the duration of mechanical ventilation and the timing of extubation. Many sedation protocols are described in the literature. The investigators aim to assess if a transdermal fentanyl-based sedation protocol can have an impact on the global Work of Breathing (WOB)

The choice of the sedation protocol has a massive impact on the duration of mechanical ventilation and the timing of extubation. Many sedation protocols are described in the literature. No data are available about the possibility of using transdermal fentanyl as an alternative to intravenous opioids during the weaning phase from mechanical ventilation and the post-extubation period until the discharge from ICU to the ward. The investigators aim to assess if a transdermal fentanyl-based sedation protocol can have an impact on the global Work of Breathing (WOB). Secondary endpoints of the study are the duration of mechanical ventilation, the duration of continuous infusion of opioids, the length of stay in ICU and in hospital. Eligible patients will be randomized in 2 groups: Group 1 will receive remifentanil; Group 2 will receive transdermal fentanyl and remifentanil. An Edi Catheter for diaphragm electrical activity monitoring will be put in place for each patient.

Statistical Analysis: Distribution normality will be assessed with the Kolmogorov-Smirnov test. Continuous variables will be reported expressed as medians (interquartile ranges). Qualitative variables will be reported as frequencies. Analysis on the primary efficacy criterion and other quantitative variables will be assessed with the Wilcoxon-Mann-Whitney test. Categorical outcomes will be compared with the chi-square test, or Fisher's exact test, as appropriate. Cochran-Mantel-Haenszel statistics will be reported for all these results. Two-way analysis of variance (ANOVA) for repeated measures with Bonferroni correction will be used to determine the differences in secondary endpoints. Comparisons between groups regarding these variables at each study time point were performed with the Student's t-test or Mann-Whitney test, as appropriate. Mean difference and 95% confidence interval [Confidence Interval 95%] are reported for most significant results. Two-tail p values≤0.05 Will be considered significant.

Inclusion Criteria:

• Age > 18 yo;
• Negative pregnancy test prior to inclusion in the study;
• The informed consent form needs to be signed and dated by the patient or a relative/legal guardian before of any procedure related to the study; if the patient is initially unable to sign the informed consent form, but later regains the ability to sign it, a new informed consent form will be given to the patient and must be signed and dated;
• Mechanically ventilated in Pressure Support Ventilation, according to the decision to the attending physician;
• A patient with prolonged weaning from the mechanical ventilator will be considered eligible. Prolonged weaning is defined as weaning that is still not terminated 7 days after the first separation attempt from the ventilator (by success or death).
• Analgesia provided by continuous infusion of remifentanil lasting five days or more and an intolerance to a dose reduction of 0.025 mcg/kg/min defined as the presence of at least one of the following criteria: RASS ≥ 2, a respiratory rate ≥ 35 breaths/minute, a PaCO2 < 30 mmHg, a heart rate > 120 bpm, a systolic blood pressure value > 160 mmHg or an increase of Visual Analogue Scale for pain assessment of ≥ 2 points.

Exclusion Criteria:

• Hypersensitivity to the active substance or any of the excipients;
• Hepatic or renal impairment;
• Fever (body temperature ≥ 38 °C) or septic shock, hypothermia (body temperature < 35 °C) or presence of active surface cooling systems;
• Hypercapnic patients with a PaCO2 > 45 mmHg;
• Current enrollment or plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days or 5 half-lives of the agent, prior to the baseline visit;
• Hypoxemic respiratory failure (P/F < 200 mmHg);
• Delirium state defined as RASS ≥ 3 and CAM-ICU positive;
• Hemodynamic instability requiring high doses of inotropes or vasopressors;
• Any condition that may contraindicate the use of remifentanil or transdermal fentanyl;
• Patients with a BMI ≥ 35;
• Patient admitted for postoperative monitoring after elective surgery;
• EAdi catheter contraindicated.