Poorly controlled postoperative pain is associated with worse clinical outcomes and negative patient experiences. Surgeons play a crucial role in optimizing postoperative pain and minimizing narcotic use. This article reviews pain management strategies available to plastic surgeons based on therapeutic class of medication and provides a framework for pain management based on Enhanced Recovery After Surgery (ERAS) protocols. The authors have developed a multimodal analgesia regimen to treat postsurgical pain. This article discusses opioids, acetaminophen, nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, gabapentin, muscle relaxants, steroids, and local anesthetics. It also discusses tumescent analgesia, regional blocks, and epidurals.
Key points
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Poorly controlled postoperative pain is associated with worse clinical outcomes and negative patient experiences.
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Plastic surgeons must be well versed in multimodal analgesia (MMA) management strategies to optimize postoperative pain control and minimize narcotic use.
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MMA regimens are customized to the patient and procedure.
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Local anesthetics, regional blocks, and epidurals are powerful adjuncts in any MMA regimen.
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Plastic surgeons must be aware of dosing and contraindications for all medications used as part of an MMA regimen.
Introduction
Postoperative pain management in plastic surgery has become a topic of increasing interest. Pain is the perceived sensory and emotional reaction to actual or perceived tissue injury. Nociceptive pain is caused by suprathreshold stimulation of peripheral pain receptors from damage to nonneural tissue. Inflammatory pain results from peripheral pain sensitization caused by activation of the immune system via chemical mediators. Surgery causes tissue injury that leads to both nociceptive and inflammatory pain. Pathologic pain is caused by dysfunction of the nervous system without tissue damage; it is maladaptive in that it serves no biological function.
Uncontrolled postsurgical pain has been associated with increased risk of poor pulmonary function, myocardial ischemia, ileus, thromboembolism, and impaired immune function. , It has been associated with increased postanesthesia care unit stays, prolonged admissions, and increased readmission rates, all of which may affect reimbursement and patient satisfaction. Uncontrolled postsurgical pain has also been implicated in the development of persistent postsurgical pain (PPSP) caused by maladaptive neuronal plasticity. , PPSP is estimated to affect 20% to 25% of mastectomy patients, 50% to 85% of amputation patients, and 5% to 35% of hernia repair patients. ,
In the era of the American opioid epidemic, surgeons play a crucial role in optimizing postoperative pain and minimizing narcotic use. Nonpharmacologic pain management strategies such as mindfulness, massage, and acupuncture have been found to be effective pain management strategies and should be used. This article reviews pain management strategies available to plastic surgeons based on therapeutic class of medication and provides a framework for pain management based on Enhanced Recovery After Surgery (ERAS) protocols. Much of this content was previously covered in a Plastic and Reconstructive Surgery Pain Management Supplement and the authors refer the reader to the supplement for a more in-depth discussion.
Opioids
Opioids are ubiquitous in the current health care system. This class of analgesics primarily act on mu opioid receptors in the central nervous system. Opioids modify afferent pain signals by binding to opiate receptors and decrease the perception of pain. The mu opiate receptor not only has analgesic properties but also causes euphoria, sedation, anorexia, and respiratory depression; this accounts for the adverse effects associated with opiate use. The addictive potential of opioids has been well established and cannot be overstated, with estimates of postoperative chronic opiate use in previously opiate-naive patients ranging from 5% to 13%.
Opioids are generally administered parenterally or orally. Parenteral administration has predictable peak plasma concentration with rapid time to onset and offset. Parenteral formulations of opioids are an effective method of analgesia in patients without enteral absorptive capacity. Patient-controlled analgesia (PCA) devices allow repeated low doses of opioids to be administered by the patient. PCA has gained popularity because it decreases nursing burden; however, PCA has been shown to increase side effects such as nausea, vomiting, and pruritis. Oral administration of opioids results in slower time of onset because of first-pass metabolism through the liver; however, the slower enteral absorption results in more steady and longer-lasting analgesic effects.
Opioids should be used with caution in patients with obstructive sleep apnea, geriatric patients, and those with abuse history or potential. Caution must be used in prescribing opioids to patients who concurrently use other sedative medications, such as benzodiazepines, antihistamines, or sleep aids, because these can have additive effects and cause respiratory depression. They should also be used with extreme caution in anyone with a history of alcohol consumption.
The authors recommend minimizing opiate use postoperatively by using a patient-specific and procedure-specific multimodal analgesia (MMA) approach for ambulatory or inpatient surgery patients. For patients who require opioids for acute postsurgical pain, we recommend the use of opioids without added acetaminophen (eg, tramadol or oxycodone alone) to decrease the risk of acetaminophen toxicity (maximum dose, 4000 mg in 24 hours).
Acetaminophen, nonsteroidal antiinflammatory drugs, and selective cyclooxygenase-2 inhibitors
Acetaminophen
Acetaminophen’s mechanism of action remains elusive but it is thought to inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes in the central nervous system. This inhibition accounts for its analgesic and antipyretic effects. , Because acetaminophen does not affect peripheral COX enzymes, it does not have the same gastric ulceration and bleeding complications associated with nonsteroidal antiinflammatory drugs (NSAIDs). A Cochran Review found that a single dose of acetaminophen postoperatively achieves a 50% reduction in pain. Acetaminophen is available in oral, rectal, and intravenous formulations. Intravenous acetaminophen is significantly more costly than oral acetaminophen and has not been shown to be more effective in reducing postoperative pain scores compared with oral acetaminophen. Acetaminophen is metabolized by the liver and must be used with caution in patients with liver disease. The maximum dose of acetaminophen is 4000 mg in a 24-hour period.
The authors recommend using acetaminophen in all postoperative patients who do not have contraindications to its use. Acetaminophen should be scheduled around the clock in the first 48 to 72 hours following surgery. Prescribers must exercise caution in patients who take medications at home containing acetaminophen, such as opioid combinations or cold medications.
Nonsteroidal Antiinflammatory Drugs
NSAIDs act by inhibiting peripheral COX-1 and COX-2 enzymes and inhibiting the synthesis of prostaglandin, a mediator of inflammation and vasodilation, and thromboxane, a mediator of vasoconstriction and platelet aggregation. NSAIDs cause gastric ulceration, gastrointestinal (GI) bleeding, platelet dysfunction, asthma exacerbation, and renal impairment. Importantly, prescribers must be aware of the cardiovascular risks associated with NSAIDs and COX-2 inhibitors. These risks include myocardial infarction, stroke, heart failure, hypertension, atrial fibrillation, and venous thromboembolism in patients with and without known cardiovascular disease, elucidated largely through the landmark Vioxx gastrointestinal outcomes research (VIGOR) and Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trials. , In 2015, the US Food and Drug Administration (FDA) strengthened its warning against NSAIDs, warning against the use of these medications because of increased risk of heart disease and stroke, both in patients with and without existing heart disease.
Cyclooxygenase-2 Inhibitors
The COX-2 enzyme plays a role in inflammation. Selective COX-2 inhibitors theoretically reduce the risk of GI bleeding. Several studies investigating the GI benefits of selective COX-2 inhibitors found they have decreased risk of GI bleeding compared with NSAIDs, but were still associated with higher bleeding risk compared with placebo. , , A study investigating the effect of selective COX-2 inhibitors on platelet function found the drugs to have similar, undetectable effects on platelet function compared with placebo, whereas NSAIDs decreased platelet aggregation and increased bleeding time. Selective COX-2 inhibitors have many of the same contraindications as NSAIDs with the exception that they have an improved GI risk profile. Importantly, they carry the same FDA warnings with regard to cardiovascular risks as NSAIDs. ,
The authors recommend selective use of NSAIDs or COX-2 inhibitors in appropriately selected patients. These medications should not be used in patients with known cardiovascular disease, renal impairment, or GI bleeding risk factors. Duration should be minimized to the acute postoperative setting and the lowest effective dosage should be used. We prefer the use of celecoxib dosed 3 times per day.
Adjuvant multimodal medications
Gabapentin
Gabapentin postsynaptically binds to dorsal horn neurons, blocking voltage-gated calcium channels, thereby decreasing neurotransmitter release. The medication is orally administered. Gabapentin is not metabolized and is renally excreted via first-order kinetics; patients with renal impairment may require dose adjustment. , Gabapentin can cause somnolence, confusion, and dizziness and should be used cautiously in geriatric patients and those with obstructive sleep apnea. High-dose gabapentin should be tapered, because abrupt cessation can cause withdrawal symptoms similar to those caused by alcohol and benzodiazepines. A meta-analysis of postoperative gabapentin use found a 35% reduction in total opioid use within 24 hours following surgery and a significant reduction in postoperative pain. However, a Cochrane Review on systemic medications for the prevention of chronic postoperative pain did not find a significant reduction of chronic postoperative pain with gabapentin.
The authors recommend the use of gabapentin as an adjunctive multimodal medication for acute, postoperative pain in hospitalized patients. We advocate a loading dose the evening before surgery (usually 600 mg) as well as a preoperative dose before the operation (typically 300 mg). Postoperatively, in patients less than 65 years old, we favor 300 mg orally 3 times a day, whereas those more than 65 years old are dosed twice daily. Gabapentin must be dose adjusted for patients with renal impairment and used cautiously in geriatric patients and those with obstructive sleep apnea.
Muscle Relaxants
Cyclobenzaprine is a commonly prescribed muscle relaxant. Despite its classification, cyclobenzaprine does not act on skeletal muscle. It is a centrally acting medication that is thought to act at the brainstem level on the locus ceruleus, decreasing the activity of serotonergic descending neurons, thus decreasing muscle tone. , The effect on the locus ceruleus may help to explain the sedating qualities of the medication. Cyclobenzaprine, and most other muscle relaxants, are renally metabolized and require dose adjustments for patients with renal impairment. For patients unable to take oral medications, methocarbamol can be administered intravenously.
The authors recommend the use of muscle relaxants as adjuncts in an MMA regimen when a patient’s pain is not controlled with a standard MMA regimen and when the operation involved a high likelihood of muscle spasm or tension. We use special caution in elderly patients because this class of medication can worsen fall risk and delirium.
Steroids
Steroids have potent and well-known antiinflammatory, immunomodulatory, and antiemetic effects. However, steroids also have innumerable side effects beyond the scope of this discussion. With regard to plastic surgery applications, steroids cause delayed wound healing, increased surgical site infections, and hyperglycemia. A single dose of dexamethasone given preoperatively or intraoperatively has been found to decrease postoperative pain scores and narcotic usage. , Two retrospective studies, a meta-analysis, and a Cochrane Review have not found significant wound healing complications or surgical site infections within 30 days after a single perioperative dose of dexamethasone; however, long-term studies are lacking.
There should be no concern or hesitation when the use of dexamethasone is warranted for its antiinflammatory or antiemetic effects. Typically, a single 8-mg intraoperative dose (Decadron) is recommended, and can be given at any time after induction. Clinicians should avoid preoperative administration because a known side effect is intense anal/perineal itching.
Topical Anesthetics
Topical anesthetics are the topical version of injectable local anesthetics. These classes of medications inactivate voltage-gated sodium channels, raising the threshold required to generate an action potential, rendering the area temporarily insensate. Their structure consists of a lipophilic aromatic group attached to an amine group with a chain of either an amide or ester. The amide or ester chain affects metabolism; amides are hepatically degraded, whereas esters are degraded by plasma cholinesterase. Esters form the metabolite para-aminobenzoic acid (PABA) and are more commonly implicated in allergic reactions. Topical and local anesthetics preferentially affect type C nerve fibers (pain fibers) rather than type A nerve fibers (proprioception and pressure fibers); patients may therefore be entirely anesthetized in the injected area but continue to feel a pressure sensation.
The most commonly used topical anesthetics include lidocaine patches; eutectic mixture of local anesthetics (EMLA) consisting of lidocaine and prilocaine; as well as a mixture of lidocaine, epinephrine, and tetracaine (LET). Time of onset, depth of penetration, and duration vary for each anesthetic based on the pKa, pH, solubility, and protein-binding potential. Skin penetration can be increased by exfoliating skin and using alcohol to cleanse skin of sebaceous material. Efficacy of topical anesthetics depends on skin permeation and has a delayed onset of action compared with locally injected anesthetics. A Cochrane Review investigating the use of topical anesthetics during repair of dermal lacerations found that they can play an important role in analgesia before laceration repair.
The concentrations of each local anesthetic vary and must be carefully calculated to avoid local anesthetic systemic toxicity (LAST) ( Table 1 ). , Surgeons must be well versed in the management of LAST; guidelines are available from the American Society of Regional Anesthesia and Pain Medicine.
| Anesthetic | Onset (min) | Duration of Analgesia (h) | Maximum Dose Without Epinephrine (mg/kg) | Maximum Dose with Epinephrine (mg/kg) |
|---|---|---|---|---|
| Lidocaine | 10–20 | 0.25–1 | 4.5 | 7 |
| Mepivacaine | 10–20 | 0.75–1.5 | 5 | 7 |
| Ropivacaine | 15–30 | 2–6 | 3 | 3.5 |
| Bupivacaine | 15–30 | 2–4 | 2.5 | 3 |
The authors recommend the use of topical anesthetics applied at least 30 minutes before planned procedure for simple laceration repairs in pediatric patients.
Local Anesthetics
The importance of local anesthetics in plastic surgery practice cannot be overstated. The most commonly used local anesthetics include lidocaine, bupivacaine, and ropivacaine. These anesthetics are often combined with epinephrine to decrease intraoperative blood loss and allow better visualization. Lalonde has revolutionized wide-awake surgery with injection techniques that minimize discomfort and maximize efficacy.
Local anesthetics not only allow painless wide-awake surgery but also improve postoperative pain. A meta-analysis found that local anesthetic injected before incision decreases somatic pain and decreases postoperative analgesic consumption and time to first rescue pain medication dose. Joshi and colleagues provide a framework for surgical site infiltration of local anesthetic for abdominal wall surgery based on a neuroanatomic approach; this framework is widely applicable.
Liposomal bupivacaine contains bupivacaine within a lipid-based vehicle that results in diffusion of the drug over time with initial peak at 0.25 to 2 hours and a second peak 12 to 24 hours after injection. Liposomal bupivacaine has been shown to provide pain relief over 48 to 72 hours. Liposomal bupivacaine remains under patent and thus costs more than standard bupivacaine. A study by Little and colleagues found decreased postoperative narcotic consumption, length of stay, direct and total costs, and 30-day readmission rate with liposomal bupivacaine compared with control patients undergoing abdominal wall, implant-based, and autologous breast reconstruction. However, a prospective, single-blinded, randomized controlled trial of a single surgeon using liposomal bupivacaine in addition to an enhanced recovery protocol including preoperative regional block failed to detect a clinical difference in total opioid consumption, pain score, or length of stay. This finding suggests that the benefits of liposomal bupivacaine are clinically insignificant when combined with an enhanced recovery protocol that includes a regional or epidural analgesia.
The authors recommend the use of short-acting local anesthetics for bedside procedures and long-acting local anesthetics for postoperative pain control. We reserve the use of liposomal bupivacaine for patients at high risk of postoperative pain (such as those undergoing abdominal wall reconstruction who did not undergo preoperative epidural block), and usually administer it as a regional block for maximum effect.
Tumescent Analgesia
Tumescent analgesia involves the use of dilute lidocaine or bupivacaine in large volumes of carrier fluid with or without epinephrine. This technique was popularized by Klein in the late 1980s for use during liposuction. The practice has since been expanded to several surgical procedures, including body contouring, mastopexy, breast reduction, and mastectomy. Because of the lipid solubility and distributive properties of local anesthetics, tumescent analgesia allows higher maximum concentrations of local anesthetics than traditional field blocks. Klein performed further studies measuring the maximum safe dose of lidocaine in wetting solution and found this to be 35 mg/kg, with more recent reports showing safety profiles up to 55 mg/kg. , The American Society of Plastic Surgeons Practice Advisory on Liposuction recommends limiting lidocaine to a maximum dose of 35 mg/kg; with adjustments for patients with metabolic conditions that may limit metabolism of local anesthetics.
There is a dearth of evidence for the analgesic effects of tumescent techniques. However, 1 prospective, double-blinded, randomized controlled trial injecting wetting solution containing lidocaine into the side of a body site undergoing liposuction found a statistically significant decrease in postoperative pain at 18 hours after surgery. However, this study did not account for the potential distributive effect of lidocaine or the systemic absorption of lidocaine, which, in itself, has been shown to decrease postoperative pain.
The authors recommend the routine use of wetting solution in a superwet manner with lidocaine or bupivacaine, as described by Fodor, within the safety profile of each respective local anesthetic for liposuction.
Regional Anesthesia
Regional anesthesia is the technique whereby long-acting local anesthetic is injected or continuously infused into a targeted area surrounding peripheral nerves supplying specific dermatomes, thereby anesthetizing entire dermatomes. Regional anesthetics have been shown to decrease postoperative narcotic use, postoperative nausea/vomiting, and length of stay. The most commonly used regional anesthetics in plastic surgery include the pectoralis nerve block (PECS) I and II block in breast surgery, transversus abdominis plane (TAP) block for abdominal wall surgery, and supraclavicular or infraclavicular blocks for wrist and hand surgery.
The PECS block is performed by injecting long-acting local anesthetic into the fascial plane between the pectoralis major and minor muscle (PECS I) and above the serratus anterior muscle at the level of the third rib (PECS II), blunting sensation from the pectoral, intercostobrachial, intercostal 3 to 6, and long thoracic nerves. The TAP block is performed by injecting long-acting local anesthetic between the internal oblique and transversus abdominis fascial planes, blunting the afferent sensory fibers of the terminal branches of T10 to L1 sensory fibers. The supraclavicular and infraclavicular blocks are performed by injecting local anesthetic around the trunks and divisions or cords of the brachial plexus, respectively. , Techniques vary but these blocks are typically performed with ultrasonography guidance; ultrasonography guidance decreases risk of pneumothorax.
Because regional anesthesia uses local anesthetics, the same caution with regard to local anesthetic toxicity must be used. The authors recommend the use of regional anesthesia whenever possible. Certain regional anesthetics, such as the PECS and supraclavicular blocks, require skilled anesthetists; these capabilities may not be available in certain settings.
Epidural Anesthesia
Epidural anesthesia blocks the spinal nerve roots as they exit the spinal cord. This blocking is done by injecting or infusing local anesthetic and narcotic medications into the epidural space. At typical doses, epidurals do not cause motor weakness and thus allow early postoperative ambulation. Epidurals are commonly used for abdominal wall reconstruction. They are typically placed preoperatively and continued for 3 to 5 days postoperatively until the patient is able to tolerate an oral MMA regimen.
Outcomes data on epidural analgesia have been mixed, with few studies specifically assessing uses within plastic surgery. A 2016 Cochrane Review by Guay and colleagues comparing epidurals with local anesthetics with opioids administered systemically or via epidural in abdominal surgery found that epidurals with opioids decrease postoperative pain and speed return of bowel function. A more recent Cochrane Review by Salicath and colleagues comparing epidural analgesia with intravenous opiate PCAs in intra-abdominal surgery noted the decrease in postoperative pain to be clinically insignificant with higher chance of epidural failure caused by technical error and episodes of hypotension requiring intervention. Khansa and colleagues studied the effect of preoperative epidural placement in an MMA regimen for abdominal wall reconstruction and found epidurals decreased postoperative narcotic requirements compared with patients who did not receive a preoperative epidural.
Epidurals have rare, but nontrivial, complications related to technique. These complications include epidural hematomas, abscesses, peripheral neuropathy, and spinal headaches. Their use is also associated with hypotension caused by efferent sympathetic blockade; this is seen in up to 33% of patients. Epidurals can also cause respiratory complications in patients with preexisting pulmonary disease because the effect on intercostal and abdominal muscles can weaken forced exhalation.
The authors recommend the use of epidural anesthesia in properly selected patients requiring inpatient reconstructive surgery, particularly abdominal wall reconstruction. We recommend the use of epidurals in combination with enhanced recovery protocols and MMA.
Putting it All Together: Multimodal Analgesia Regimen
In a time when the United States faces an opiate epidemic, surgeons must be ever mindful of their postoperative analgesic approach. The era of ERAS protocols, pioneered by Ljungqvist and colleagues , in the early 2000s, opened the surgical community’s eyes to the benefits of preoperative nutritional and functional optimization, early postoperative liberalization of diet, and MMA. The authors have adapted the lessons learned from the ERAS protocols as well as our own institutional experience to develop an MMA regimen to treat postsurgical pain. , , Table 2 summarizes our recommendations for MMA options that can be customized based on surgical procedure and patient characteristics.
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