**13. Opioids**

## **13.1 Tramadol**

Tramadol is a synthetic, centrally acting analgesic agent with 2 distinct but complementary mechanisms of action: selectivity for μ receptor, although it binds weakly to the δ and κ receptors. The affinity for the μ receptor is ≈6000 fold less than morphine and 10-fold less than codeine. Inhibits reuptake of noradrenaline (norepinephrine) and 5-HT. Causes no clinically relevant respiratory depression in adults or children undergoing surgery and there are no clinically significant changes in oxygen saturation in adults and children receiving tramadol. In healthy adult volunteers and patients who underwent abdominal surgery, tramadol had no clinically relevant effects on gastrointestinal functioning [65].

Three studies evaluated the effects of tramadol on postoperative pain, opioid consumption, and complications after primary total joint arthroplasty (TJA). One high quality study compared the use of tramadol versus a placebo for treatment of pain after TJA. Another high-quality study compared tramadol to placebo and to paracetamol with codeine. One additional high-quality study compared tramadol to other opioid medications for treatment of pain after TJA. There were mixed results among all studies on the effects of tramadol on pain, patient-reported outcome scores, opioid consumption and adverse events after TJA. Adverse events including dizziness, dry mouth, and nausea were more common among patients who received tramadol compared to placebo. Given the conflicting evidence with regards to opioid consumption, the fact that two studies evaluated intravenous tramadol which is not approved by the Food and Drug Administration in the United States, and that there was inconclusive evidence comparing the efficacy of tramadol to other opioids the strength of the recommendation was downgraded to moderate [66–68].

#### **13.2 Morphine**

Immediate release opioids are preferred in the management of postoperative pain when simple analgesics are insufficient to achieve the analgesic goals. If modifiedrelease opioid preparations (including transdermal) are used, due care should be exercised as they have been associated with harm. The prescribed dose of the immediate release opioids should be age related (rather than weight) and take into account renal function. Immediate-release oxycodone is not recommended as a first line opioid, because is more labor intensive to administer. However, it is recognized that in elderly patients over 70 years or in patients with renal failure, other opioids may be used post operatively [69].

#### **13.3 Oxycodone**

Oxycodone is a semisynthetic, μ-opioid receptor agonist with analgesic effects in several pain conditions. Acts also on κ-opioid receptors. Oxycodone and morphine are presumed to have a 1:1 ratio of analgesic potency in postoperative pain after surgery, with mixed somatic and visceral pain components. Oxycodone is metabolized by the cytochrome P450 enzyme system in the liver [70]. Shows the same adverse effects as those typically found for opioids, with constipation (25–30%), nausea (25–30%), and drowsiness (25%) being the three most common symptoms. Vomiting, pruritus, and dizziness occur in 5%–15% of patients taking oxycodone [71]. The potency ratio of

oxycodone to fentanyl is less than 75:1. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age.

Oxycodone for somatic pain such as pain after orthopedic surgery, the amount of oxycodone should be higher than the dose used for visceral pain. In a study of seventy-three patients undergoing orthopedic surgery randomly assigned to receive fentanyl or oxycodone using intravenous PCA, they concluded that with a 1:60 ratio of oxycodone to fentanyl in the application of PCA for pain control, the use of larger doses of oxycodone for 6 hours is effective in controlling early postoperative pain [72].

#### **13.4 Transdermal buprenorphine**

It is more described for chronic pain management, that persists for 12 weeks or more despite analgesia [73]. The role in the clinical management for acute pain is less clear, but it has been evaluated in the postoperative setting of hip fracture surgery, knee or hip arthroscopy/arthroplasty, shoulder surgery and spinal surgery. Is a partial agonist at the μ-opioid receptor [74, 75]. When the patch is applied prior to surgery and left in place for the prescribed seven days, it is associated with reduce postoperative pian, lower consumption of other analgesics, and patient satisfaction.

Is an opioid and a Schedule III controlled substance which means it is considered less dangerous tan Schedule II substances, such as morphine or oxycodone [76]. Buprenorphine has a ceiling effect for respiratory depression, meaning that the risk for opioid-induce respiratory depression does not increase beyond a certain dose. Has hepatic metabolization, it is safe for patients with renal dysfunction. This means buprenorphine can be administered to elderly patients and those with renal dysfunction without the need to adjust the dose [77].

The transdermal buprenorphine patch is available in 5, 10 and 20 μg/h doses and other doses can be achieved by cutting the patch or using two patches. The transdermal buprenorphine patch is to be discontinued after seven days with the plan of switching the patient to an oral opioid or some other pain reliever, it is recommended that the buprenorphine patch be removed and 24 hours elapse before the new medication is started. Based on recent clinical trials, buprenorphine is 75–100 times more potent than morphine [78].

#### **14. Conclusion**

Any general or regional anesthetic technique must always be tailored to the individual patient and the procedure, taking the potential benefits and risks into account. The contribution of the individual anesthesiologist in managing the RA or GA (regional anesthesia or general anesthesia) technique effectively and safely in order to obtain a positive outcome should not be undervalued. In spite of this, evidence suggests that RA confers additional benefits beyond the reduction of acute pain. These include a distinct reduction in pulmonary complications and a reduction in chronic pain after certain procedures. RA has also been associated with a reduction in cancer recurrence, blood transfusion, severe sepsis, intensive care unit admissions, and even a small reduction in mortality in some cases; however, these findings should be interpreted with greater caution. When CNB (central neuraxial blockade) is administered alone, as opposed to in conjunction with GA, the benefits are frequently greater. Logically, utilizing PNBs without GA and thereby avoiding CNB-mediated

*Postoperative Pain in Orthopedics DOI: http://dx.doi.org/10.5772/intechopen.111880*

hypotension may offer the greatest benefit; however, the potential outcome advantages of PNBs are the area that has received the least amount of research.

Definitely postoperative pain can have a significative impact in the physiology of the body, including the activation of inflammatory mediators and changes in cardiovascular, respiratory and GI function. The understanding of these physiological alterations is of vital importance for the correct treatment of postoperative pain and possible postoperative complications.
