*3.1.3. Fentanyl*

Fentanyl is 80–100 times more potent than morphine and it may cause less respiratory depres‐ sion when compared with morphine. It has no active metabolites, and it has a wider therapeutic index than morphine in preclinical models [39].

In a retrospective cohort study of 8955 patients who received one of the three opioids for post‐ operative pain (morphine, fentanyl or meperidine), the incidence of respiratory depression was 0.6% in the group of patients who received fentanyl, compared to 2.8% among patients who received morphine [40]. Although apparently it may be associated with smaller risk of respiratory depression when compared to morphine, fentanyl can be associated with more device programming errors, since this drug is dosed in micrograms [40, 41].

Because of its high lipid solubility, fentanyl has a pharmacokinetic profile characterized by a rapid onset and short action. Therefore, some patients may need doses too frequently or require a basal infusion rate, which greatly increases the risk of respiratory depression. Due to its high volume of distribution, prolonged administration may result in a significant increase in drug half‐life, with consequent raise in the incidence of adverse effects [42]. Given these pharmaco‐ kinetic characteristics, there are complaint reports of patients after fentanyl administration in IV‐PCA [43].

Doses and recommended parameters: demand dose: 20–50 µg; lockout: 5–10 min; Basal continuous: 0–60 µg/h [11].

## *3.1.4. Sufentanil*

Sufentanil is a fentanyl analog, being about 5–10 times more potent than Fentanyl itself. It rep‐ resents the opioid with greater therapeutic index (25,000) used for postoperative pain in pre‐ clinical studies [39]. The high therapeutic index is clinically relevant for evoking a decreased risk of incidence of respiratory depression compared to morphine, fentanyl, and alfentanil [44]. In a randomized clinical trial with 30 volunteers, it was noted that sufentanil provided more effective analgesia and less respiratory depression when compared with fentanyl [44].

Sufentanil is highly lipophilic (twice more lipophilic than fentanyl) and it provides rapid onset of action and shorter effect duration when administered intravenously to PCA, justifying its rare use in this route. However, unlike fentanyl, its half‐life of elimination does not increase with infusion time and it shows paradoxical increase in their concentration during the elimina‐ tion phase [39]. A randomized clinical trial that compared plasma levels of sufentanil and fen‐ tanyl in 41 patients undergoing coronary artery bypass surgery, demonstrated the occurrence of peak plasma concentration (increase of 29–49%) from 4 to 15 h after administration *bolus* of fentanyl. On the other hand, only one patient had sufentanil treated with this paradoxical effect (43% increase). This peak in plasma concentration explains the occurrence of late respiratory depression in patients treated with fentanyl [45]. Therefore, considering their high therapeu‐ tic index and predictable pharmacokinetic profile, sufentanil represents a promising example of opioid that could be used to PCA cases requiring short duration of effect and availability intravenously.

The doses and the usual parameters are: demand dose: 4–6 µg; lockout: 5–10 min; continuous baseline: 0–8 µg/h [11].
