*3.1.1 Opioids*

Although opioids are the cornerstone in the treatment of POP, unfortunately plastic surgeons prescribe almost twice as many opioids as are required after outpatient surgeries, which continues to be a major factor in the globalized crisis of legal and illegal use of these drugs [12, 25–27]. Just to mention an example, in body-contouring surgeries, opioid overprescription is a proven routine among plastic surgeons. Bennett et al. [28] examined health insurance claims between 2001 and 2015 of patients with no history of opioid use who underwent body-contouring surgeries (abdominoplasty/panniculectomy, breast reduction, mastopexy, brachioplasty, and thigh plasty). They found that 6.1% of patients who had not previously received opioids developed persistent new use and 12.9% were exposed to high-risk prescriptions. Persistent opioid use was higher in high-risk prescription patients (9.2%), being the highest in thigh plasty (17.7%; 95% CI, from 0.03 to 0. 33). These researchers found high rates of mood disorders, anxiety, smoking, alcohol intake, neck pain, arthritis, and other pain disorders. In a study [29] of 56,773 patients undergoing body-contouring surgery, it was found that hydrocodone with paracetamol was the most prescribed opioid with an average of 17.9 days. These authors examined the comorbidities in this group of patients, finding that the cases with peripheral vascular disease and smoking were prescribed more opioids than patient without peripheral vascular disease (871.97 vs. 535.41; p < 0.001) and smoking (1069.57 vs. 440.84; p < 0.001). Those patients who developed surgical site infection, disruption of wound, and venous thromboembolism were prescribed a considerably greater dose of opioids (1213.63 vs. 561.59; p < 0.001). Another example of opioid overuse is augmentation mammoplasty where

up to 91.2% of surgeons prescribe opioids, the most recommended being oxycodone with acetaminophen 47%, and hydrocodone with acetaminophen 38.3% [30].

Opioids primarily act on mu, kappa, and delta opioid receptor modulating the algesic response. Mu opiate receptor properties also include euphoria, sedation, anorexia, nausea, vomiting, respiratory depression as well as tolerance and opioid addiction. When prescribing opioids, it is important to consider patients' previous health conditions which could require chronic opioid use, or those conditions which may require higher doses in geriatric patients or patients with obstructive sleep apnea in which opioids may lead to airway obstruction.

Oliceridine is a new complex opioid, with potency similar to morphine, with no ceiling effect, which has fewer side effects than traditional opioids, although it can cause respiratory and CNS depression. It was approved by the US Food and Drug Administration in August 2020 for the intravenous treatment of moderate-to-severe acute pain in hospitalized patients. Although there is still not enough research on POP in plastic surgery, oliceridine could have a prominent place in these patients [31, 32].

#### *3.1.2 Non-opioids*

Acetaminophen (paracetamol) is one of the most frequently used analgesic agents. Despite the fact that it has been used for more than a century, its mechanism of action is not fully known, and is related to inhibition of CNS enzyme cyclooxygenase (COX) activities, with conflicting views on the COX isoenzyme/variant targeted by acetaminophen and on the nature of molecular interactions with these enzymes. It appears to selectively inhibit COX-2 by functioning as a reducing agent, although *in vitro* screening tests demonstrate low potency in inhibiting COX-1 and COX-2. In COX-1 transgenic mice, acetaminophen works through the inhibition of a variant of the COX-1 enzyme to mediate its analgesic and particularly thermoregulatory actions (antipyresis and hypothermia). Another possibility is that the descending inhibitory serotonergic pathway is potentiated to mediate the analgesic action of paracetamol, but without evidence of binding to serotonergic molecules. It has been proposed that AM404 (*N*-acylphenolamine), a paracetamol metabolite, activates the endocannabinoid1 and transient receptor potential vanilloid-1 (TRPV1) brain systems. Also, AM404 directly induces analgesia *via* TRPV1 receptors on terminals of C-fibers in the spinal dorsal horn [33, 34]. Consequently, acetaminophen induces analgesia by acting not only on the brain but also on the spinal cord.

It does not have the same gastric complications as other NSAIDs. A single dose of acetaminophen may reduce pain by 50%. However, its administration should be reduced in patients with liver malfunction, limiting its total dose to 2000 mg/day. In healthy patients, its total dose in 24 h should not be over 4000/day mg. Liver damage from acetaminophen is a rare secondary effect related to overdose.

#### *3.1.3 Non-steroidal anti-inflammatory drugs (NSAIDs)*

It is a group of non-opioid analgesics widely used in POP, although its potency is less than that of opioids and its side effects are extensive, especially with long-term use. Selective COX-2 inhibitors are linked to greater cardiovascular risk, while nonselective COX inhibitors are associated with higher gastrointestinal hazard. NSAIDs with lower renal excretion with phase 2 metabolism are less likely to induce adverse effects and drug-drug interactions [35].

#### *Postoperative Analgesia in Plastic Surgery Procedures DOI: http://dx.doi.org/10.5772/intechopen.112930*

NSAIDs, which act in COX-1 and COX-2, have demonstrated a suitable analgesic effect. However, many patients have restrictions on their administration due to the higher risk of bleeding. In 2021, a meta-analysis showed that in 151,031 surgical procedures, including esthetic surgeries, the NSAIDs were unlikely the cause of postoperative bleeding. Even though NSAIDs have little to no effect on bleeding, the difference in COX-1 and COX-2 is evident when we analyze platelet dysfunction. For nonselective COX-1, the platelet dysfunction was greater than with COX-2 inhibitors. According to Schoenbrunner et al., the best NSAID for plastic surgery has been meloxicam due to its one-day administration basis and the affinity to COX-2, which decreases its action in platelet function [6, 22]. COX-2 selective inhibitors are contraindicated in those with preexisting coronary artery disease because of their association with higher rates of cardiac events. COX-2 selective inhibitors and NSAIDs should also be avoided in patients with chronic or acute renal disease [26].

It has been shown that diclofenac associated with beta-lactam antibiotics could be useful in surgical infections caused by methicillin-resistant *Staphylococcus aureus* (MRSA) where implants are used [36], which would represent a considerable advance in augmentation mammoplasty with implants.

#### *3.1.4 Other types of analgesics and adjuvants in POP*

There is a group of drugs that are used as adjuvants in postoperative analgesia that have proven to be useful, although their advantages are still controversial [37–39]. Some of these drugs are reviewed below.

#### *3.1.4.1 Gabapentinoids*

These drugs are specific ligands for the α2δ-1 subunit of voltage-gated calcium channels. Gabapentin, pregabalin, and mirogabalin have various pharmacological effects including antiepileptic, anti-anxiety, and analgesia, although this last effect is still controversial [40, 41]. A meta-analysis with 6201 patients found that the analgesic effect of both drugs is related to the doses used; pregabalin (≥150 mg) was more effective than 75 mg, and gabapentin (≥900 mg) if needed [38].

#### *3.1.4.2 Ketamine*

It is an extraordinary drug derived from phencyclidine. Synthesized in 1962 by Calvin Stevens at Parke Davis, it was first used in clinical anesthesia in 1965 by Corsen and Domino. It is a racemic mixture consisting of (S)- and (R)-ketamine, uncompetitive N-methyl-D-aspartate receptor antagonist. Although best characterized for its dissociative anesthetic properties, ketamine also has analgesic, anti-inflammatory, and antidepressant actions. It has been used as part of multimodal analgesia, from the pre-emptive phase, in the intraoperative period or in the immediate postoperative period. Sub-anesthetic doses of ketamine administered before induction or during trans-anesthesia have shown an analgesic effect in the postoperative period. It also has an important reduction in opioids and may reduce the hyperalgesia related to opioids [39]. Hallucinations are a disadvantage, although they are rare and can be prevented with a benzodiazepine administered as part of the preoperative medication.

#### *3.1.4.3 Alpha-2 agonists*

Alpha-2 adrenergic receptors are found in the central and peripheral nervous system, specifically in the pontine locus ceruleus, spinal cord tracts, rostral ventrolateral cord, and dorsal horn of the spinal cord. Clonidine, dexmedetomidine, and tizanidine are alpha-2 agonist drugs that modulate these centers, producing analgesia, sedation, bradycardia, and vasodilation without respiratory impairment. Its adjunctive effects to anesthesia are well known and are used as fundamental component of multimodal analgesia. In addition to their analgesic effect, they have been shown to reduce the use of perioperative opioids [18, 42–46].

#### *3.1.4.4 Glucocorticoids*

The use of glucocorticoids for postoperative pain is still controversial. They have a powerful anti-inflammatory effect through which their analgesic effect is hypothesized. Dexamethasone and methylprednisolone are the most used and can be administered perioperatively. They have also been used to reduce rebound pain that occurs with peripheral nerve blocks [47–49].

#### *3.1.4.5 Metamizole (Dipyrone)*

It is a non-opioid analgesic that has been demonized in some European countries and in the USA due to the possibility of death secondary to agranulocytosis, although it is one of the most used analgesics in the world since 1970. Its mechanism of action continues to be a question, having attributed to the inhibition of prostaglandin synthesis in peripheral tissues and in the central nervous system. Another recent theory mentions the modulation of CB1 and CB2 cannabinoid receptors [50, 51]. A randomized, double-blind, multiple-dose study in plastic surgery patients compared intramuscular metamizole 1 g (every 8 h) versus intramuscular diclofenac 75 mg (every 12 h), observing that dipyrone considerably decreased the requirement for meperidine as rescue analgesic in the first 18 h after surgery. This was also associated with significantly lower pain scores in patients receiving metamizole. Diclofenac had reduced side effects with thrombocytopenia and prolonged bleeding time in most patients [52].

At Lotus Med Group—a center specialized in plastic surgery—we use the analgesic management shown in **Table 1**, adjusting the doses according to the type of surgery, patient, analgesic response, and secondary effects. We believe that pre-emptive, intraoperative, and preventive multimodal analgesia is the best approach for the correct management of POP in plastic surgery. Of course, the analgesic approach must always consider an empathetic and pleasant environment for each patient, offering continuous follow-up in the immediate and mediate postoperative period. Using this analgesic approach, we have not had cases of persistent postoperative pain.

#### *3.1.4.6 Local anesthetics*

Local anesthetics (LA) inhibit neuronal action potentials *via* voltage-gated sodium channel blockade. LA for postoperative analgesia is a safe option as long as the total doses administered are monitored to avoid dangerous side effects, including death. These drugs can be administered by injection into the wound, subcutaneously, by tumescent infiltration, intravenously, by the neuroaxial route, in peripheral nerve


#### **Table 1.**

*Perioperative analgesia plan for adult patients in plastic surgery.*

blocks, interpleural, or in transdermal patches. Local infiltration of LA is a simple technique widely used by plastic surgeons; from the various tumescent solutions where local anesthetics are mixed—primarily lidocaine—to some regional blocks. LA toxicity is a controversial issue among anesthesiologists and plastic surgeons. The maximum safe doses of tumescent lidocaine have been reported to be 28 mg/ kg without liposuction and 45 mg/kg with liposuction, doses that produce serum lidocaine concentrations below toxic levels [53]. The American Society of Plastic Surgeons Practice Advisory on Liposuction recommends not to exceed a maximum dose of 35 mg/kg and only as part of a wetting solution [54]. Intravenous perioperative lidocaine decreases the incidence and intensity of chronic postoperative pain: initial bolus dose of 1.5 mg/kg followed by a continuous lidocaine infusion of 1.5 mg/ kg during surgery.

#### **3.2 Regional analgesia**

The role of regional anesthesia to treat POP in plastic surgery procedures has been widely discussed [22–24, 55, 56]. Some authors suggest that this method of analgesia may reduce the incidence of pain by many mechanisms. Blocking the nerves interferes the transmission of nociceptive input from peripheral nerves, giving as result the reduced inflammation of the nerves and the activation of glial cells. This technique also reduces the opioid consumption during and after surgery, decreases PONV, and cuts lengths of stay as well as costs. Regional blocks as well as neuroaxial analgesia are extensively used in many specialties and have become a component of many Enhanced Recovery After Surgery (ERAS) protocols. Epidural analgesia has demonstrated to improve pain management at 1 year after surgery, and recent studies have shown that peripheral nerve blocks have the same analgesic outcomes [57].

#### *3.2.1 Peripheral nerve blocks*

The increasingly frequent use of ultrasound-guided peripheral blocks favors the anesthetic and analgesic effects, decreasing side effects and complications, improves

#### **Figure 1.** *Left pneumothorax secondary to intraoperative intercostal block for POP in breast implants.*

comfort and quality of recovery of the patient, and decreases chronic post-surgical pain and dependence on opioid drugs. In plastic surgery, the most used for mammary surgery are PEC I and II, erector spinae plane block, and thoracic paravertebral blocks, and some surgeons like to perform proximal intercostal nerve blockade.

Although some studies have mentioned the possibility that PECS blockade combined with multimodal analgesia does not reduce intraoperative and/or PACU opioid consumption in women undergoing ambulatory breast surgery [58], the metaanalysis by Grape et al. [59] including 1026 patients in 16 trials concludes that there is moderate-to-high-level evidence that PECS blocks provide postoperative analgesia after breast surgery when compared with no regional technique. Ahiskalioglu et al. [60] evaluated the use of bilateral ultrasound-guided serratus plane block in 40 patients undergoing breast reduction, concluding that it is a safe technique in the treatment of POP, in addition to reducing the consumption of opioids.

Intercostal blocks are easy to perform, although they have some complications such as rapid absorption of LAs and, of course, the possibility of pneumothorax, as shown in **Figure 1**.

For abdominoplasty, the transversus abdominis plane (TAP) block, rectus abdominis muscle block, and erector spinae plane block [60–62], as well as analgesia by tumescent infiltration using lidocaine, ropivacaine, or levobupivacaine [63, 64], produce excellent relief of POP.

### **4. Conclusions**

The prevention and treatment of POP are mandatory in the comprehensive management of patients undergoing plastic surgery—be it cosmetic or reconstructive since moderate-to-intense post-surgical pain generates negative physiological changes that affect rapid recovery, prolong hospitalization, higher readmission rates, high costs, and interference with patient satisfaction. Multimodal analgesia has proven to be the best regimen in the comprehensive management of these patients, requiring an approach that includes medications combined with non-pharmacological techniques.

Although opioids have been the cornerstone in the treatment of pain secondary to surgery, the indiscriminate use of opioids for POP should be avoided.

Proper management of POP is an important determinant in the rapid recovery of patients and the return to their daily activities.
