*3.1.5. Tramadol*

meperidine, morphine, and sufentanil) showed that after meperidine (proscribed, 67.9%), the opioid with the highest incidence of central nervous system side effects was hydromorphone

Due to the similarity between morphine and hydromorphone, errors have been reported in programming the IV‐PCA pump. Considering that these agents have significant differences in their clinical potency, inadvertent hydromorphone administration can result in serious

Doses and recommended parameters are: demand dose: 0.2–0.4 mg; lockout period: 6–10 min;

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

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

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

Doses and recommended parameters: demand dose: 20–50 µg; lockout: 5–10 min; Basal

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

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

effective analgesia and less respiratory depression when compared with fentanyl [44].

device programming errors, since this drug is dosed in micrograms [40, 41].

(42.7%). Furthermore, at higher doses, hydromorphone can cause excitation [37].

complications [38].

*3.1.3. Fentanyl*

IV‐PCA [43].

*3.1.4. Sufentanil*

continuous: 0–60 µg/h [11].

continuous basal infusion dose: 0–0.4 mg/h [11].

52 Pain Relief - From Analgesics to Alternative Therapies

index than morphine in preclinical models [39].

Tramadol acts on opioid receptors with higher affinity for κ receptors than δ and µ receptors. It has an active metabolite, mono‐O‐desmethyl (M1), which has analgesic effect. In addition to the opioid agonist activity, tramadol analgesia is also promoted by inhibiting the central norepinephrine and serotonin reuptake. Tramadol potency compared to morphine is approx‐ imately 0.1. Several studies have shown that tramadol is a safe and an effective option for PCA, but with a higher incidence of nausea and vomiting [46, 47]. The recommended doses are: demand dose: 10–20 mg; lockout: 6–10 min; continuous baseline: 0–20 mg/h [11].

### *3.1.6. Oxycodone*

Oxycodone is an opioid µ receptor agonist indicated for the treatment of moderate to severe pain. Despite being most frequently used orally, in recent years, its intravenous use has increased. Its potency is about 1/75 of fentanyl, and in some studies has shown great potency up to 1/60 [48, 49].

A randomized clinical trial with 82 patients compared IV‐PCA with oxycodone and fentanyl. In this study, oxycodone demonstrated potency of 1/55 of fentanyl for the same levels of anal‐ gesia, being equally safe and the same incidence of adverse effects such as nausea, vomiting and sedation [45]. It is a drug with good efficacy and a promising role in the practice of PCA. Its use must be made on demand associated with basal infusion. The recommended doses are: demand bolus: 1 mg; lockout: 15 min; background infusion rate: 1 mg/h [50].

## *3.1.7. Other drugs*

Other opioids have been less used in IV‐PCA. The alfentanil, probably due to their pharma‐ cokinetic characteristics, did not show good results and a demand dose was not established to present a satisfactory analgesia [51]. The remifentanil, because of their ultrashort half‐life, does not have a favorable profile for PCA with some indication for analgesia for a short period such as during labor [52].

Other drugs have been used by some authors that are normally associated with morphine. Ketamine, which is an agonist of the NMDA receptor, and naloxone, which is an antagonist of opioid receptors, have shown conflicting results regarding the safety or quality of analgesia, and more studies are needed so that they can get their recommended use [18].
