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Anesthesia and pain management in plastic surgery
Introduction
Pain management before, during, and after any procedure is a key component to successful outcomes in plastic surgery. Consistent patient satisfaction hinges largely upon favorable impressions and recollections of the surgical experience. As such, patient satisfaction and pain management protocols must be effective, dynamic, multimodal, and customizable.
Pain is a self-reported, complex, and subjective experience commonly defined as an unpleasant sensory and emotional experience due to actual or potential tissue damage. The perception of pain involves both the peripheral and central nervous system. Both spinal and supraspinal sites play a role in the perception of pain within the central nervous system. Pain can be generally classified into physiologic and pathologic pain. Physiologic or nociceptive pain is acute in nature and serves as a warning or protective function, thus promoting healing and rendering it physiologically useful. In contrast, chronic pain (e.g., neuropathic) persists beyond the period of healing rendering it nonprotective and maladaptive; it is otherwise classified as pathologic pain.
Historically, pain protocols have relied heavily on opioid-based therapies which have several inherent drawbacks. The etiology of pain is often multifactorial, and therefore successful treatment depends on a multimodal approach. Analgesic regimens should target the peripheral nociceptors at the site of tissue injury, peripheral nerves supplying the surgical area, and both spinal and supraspinal sites. This multi-targeted strategy provides highly effective pain management while minimizing the adverse effects of single-agent strategies.
This chapter will focus on current concepts in pain management in plastic surgery while drawing on several themes, including:
- 1.
Multimodal analgesia with an emphasis on opioid reduction
- 2.
Neuraxial analgesia such as epidural, paravertebral, and peripheral nerve blocks
- 3.
Field blocks
- 4.
Systematic extensive surgical site infiltration with long-acting local anesthetics.
Clinical consequences of inadequate pain relief
Despite new strategies and evolving pain management regimens, postoperative pain remains one of the primary concerns of patients undergoing surgery. Approximately 80% of patients report acute pain after surgery with the majority experiencing moderate-to-severe pain. The clinical manifestations of inadequate pain management include myocardial ischemia, impaired pulmonary function, ileus, thromboembolism, impaired immune function, anxiety, and the development of chronic persistent postoperative pain ( Table 10.1 ). Pain that persists after surgery is common and has been well described in women after breast surgery. Some studies demonstrate pain one year after breast surgery (mastectomy, reduction, augmentation) to range from 22% to 49%. The etiology of persistent pain is multifactorial, including nerve injury from surgery, radiation, and chemotherapy, and phantom breast pain. Multimodal analgesia may reduce the incidence of persistent postoperative pain.
Table 10.1
Consequences of inadequate pain control
Modified from Baratta JL, Schwenk ES, Viscusi ER. Clinical consequences of inadequate pain relief: barriers to optimal pain management. Plast Reconstr Surg . 2014;134(4 Suppl 2):15S–21S.
| Organ system | Physiologic response |
|---|---|
| Cardiovascular | Increased cardiac work, ischemia, and infarction |
| Pulmonary | Increased splinting and decreased ambulation and vital capacity→ Increased atelectasis, hypoventilation, and pulmonary infections |
| Gastrointestinal | Reduced intestinal motility, increased ileus and nausea and vomiting |
| Hematologic | Decreased ambulation→ Increased venostasis, increased risk of DVT |
| Immunologic | Possible association with altered immune response→ Possible increased wound infections |
| Neurologic | Persistent postoperative chronic pain |
| Psychologic | Anxiety, fear, depression, poor patient satisfaction |
DVT, Deep vein thrombosis.
Inadequate management of postoperative pain also results in significant increases in healthcare costs by way of prolonged post-anesthesia care unit stay, delayed discharge, and readmission. Furthermore, inadequate pain control may decrease quality of life and delay recovery and the return to normal activities.
The clinical impact of inadequate pain control in the perioperative period is significant, casting an array of effects on multiple organ systems. The potential for postoperative wound infections is particularly concerning in plastic surgery. Surgical stress induces an inflammatory reaction and the release of a number of humoral mediators along with increased levels of cortisol during surgery. Together, these substances can have detrimental systemic effects, including hyperglycemia, catabolism, impaired immune function and wound healing. This physiologic and sometimes detrimental stress response to surgery may be mitigated through adequate analgesia.
Opioid use disorder is a significant concern for any physician that prescribes opioids and adequate postoperative pain control may play a significant role in reducing the risk of this abuse. Multimodal pain therapy reduces the postoperative pain experience, and it reduces opioid use. The focus on chronic pain as a driver of opioid prescribing may be misguided. Opioid prescriptions for acute postoperative pain may explain most of the excessive opioid prescribing patterns. Two studies in hand surgery patients demonstrated a significant percentage (8–13%) that continued to use opioids at 90–120 days. Even pediatric patients were not free from the pattern of overprescribing. In a 2016 study investigating pediatric opioid prescriptions, 90% were prescribed by surgeons and the average quantity prescribed was sufficient for over 7 days.
Acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 selective inhibitors
Historically, opioids have been used successfully for pain management in plastic surgery procedures, however, the risk of opioid use disorder and the opioid side-effect profile should limit routine use. For those procedures that do not involve surgical manipulation of major muscle groups or osteotomies, pain management can usually be fulfilled with non-opioid medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and local anesthetics. The advent of cyclooxygenase (COX)-2 selective inhibitors (Coxibs), as well as drugs such as gabapentin/pregabalin, clonidine, and low-dose ketamine have added new dimensions in the armamentarium of plastic surgery procedures. See Table 10.2 for dosing and Table 10.3 for pharmacology.
Table 10.2
Nonsteroidal anti-inflammatory drugs (NSAIDs) dosing
| Generic name | Brand name ( ® ) | Dose (mg/kg)/Frequency | Maximum ADULT daily dose (mg) | Comments |
|---|---|---|---|---|
|
|
|
4000 |
|
|
|
|
4000 |
|
|
|
|
3200 |
|
|
|
|
1500 |
|
|
|
|
60 |
|
|
|
|
400 |
|
BID, Twice a day; COX-2, cyclooxygenase-2; GI, gastrointestinal; IM, intramuscular; IV, intravenous; MI, myocardial infaction; PO, by mouth; q, every.
Table 10.3
Pharmacology of acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 selective inhibitors
From Gupta A, Jakobsson J. Acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 selective inhibitors: an update. Plast Reconstr Surg . 2014;134(4 Suppl 2):24S–31 S.
| Bioavailability | Peak plasma concentration | Plasma half-life | Duration of action | |
|---|---|---|---|---|
| Acetaminophen oral (1 g) | 85–95% | 10–90 min | 2–3 h | 4–6 h |
| Acetaminophen IV (1 g) | 100% | 5–10 min | 2.7 h | 4–6 h |
| NSAIDs | ||||
| Indomethacin (50 mg) | 90% | 1 h | 4.5 h | 4–6 h |
| Ibuprofen (400 mg) | ? | 1–2 h | 2 h | 4–6 h |
| Diclofenac (50 mg) | 60–70% | 15–80 min | 1.2–2 h | 4–8 h |
| Ketorolac IV (30 mg) | 100% | 10–15 min | 4–9 h | 11 |
| COX-2 inhibitors | ||||
| Etoricoxib (120 mg) | 100% | 1 h | 22 h | 20 h |
| Parecoxib a IV (40 mg) | 100% | 10–15 min | 8 h | 15 h |
COX-2, cyclooxygenase-2; IV, intravenous; NSAIDs, nonsteroidal anti-inflammatory drugs.
a Parecoxib is a prodrug and is convened to the active form valdecoxib rapidly in the liver.
Acetaminophen
Though less potent than NSAIDs or Coxibs, acetaminophen is the most frequently prescribed analgesic for the treatment of acute pain. It is often preferred because it is well tolerated. Despite the similarities to NSAIDs, the precise mechanism of action of acetaminophen is unclear. It is believed to act via inhibition of COX-1 and COX-2 enzymes through metabolism by the peroxidase functions of these enzymes both centrally and peripherally. Additional peripheral effects may be attributable to inhibition of isoforms of COX-1, COX-2, and COX-3 enzymes involved in prostaglandin synthesis, thereby increasing the pain threshold. Acetaminophen is available in oral, rectal, and intravenous (IV) formulations, and is both analgesic and antipyretic at therapeutic doses with a dose-dependent efficacy. The maximum recommended daily dose in adults without hepatic or renal disease is 4 grams with dose reduction recommended in patients with liver insufficiency. Acetaminophen in most studies demonstrates a reduction in opioid requirements and should be part of every multimodal analgesic plan (unless contraindicated).
IV acetaminophen produces a rapid and predictable plasma concentration, and is recommended as a first-line agent for the treatment of pain and fever in adults and children if oral administration is not possible. The analgesic efficacy of acetaminophen has been demonstrated in double-blind clinical trials. Efficacy of single dose, or multiple doses of IV acetaminophen (1 g) was significantly greater than placebo in adult patients who had undergone dental, orthopedic, or gynecologic surgery.
When used in therapeutic doses, acetaminophen is a relatively safe drug with few and mild side effects. In comparison to opioids, there is no effect on respiratory drive, and furthermore, it does not cause sedation, nausea and vomiting or reduced gastrointestinal motility. Furthermore, the effects on platelets and hemostasis are insignificant in patients without a history of coagulopathy. There are no significant cardiovascular, renal, or pulmonary side effects. The most significant side effect is hepatotoxicity when administered in high doses, chronic use, or when administered with alcohol or other various hepatotoxic drugs. Very rare side effects include blood dyscrasia (i.e., thrombocytopenia), methemoglobinemia, and hemolytic anemia.
Nonsteroidal anti-inflammatory drugs
NSAIDs have been used effectively for the treatment of acute and chronic pain for several decades. The primary mechanism of action is through the inhibition of both COX-1 and COX-2 enzymes, thereby inhibiting the synthesis of thromboxanes and prostaglandins. NSAIDs have well-established analgesic, antipyretic and anti-inflammatory properties. Pharmacokinetic data and selectivity of action are shown in Tables 10.3 & 10.4 .
Table 10.4
Opioid dosing
| Agonist (Brand name®) | Equipotent IV dose (mg/kg) | Equipotent PO dose(mg/kg) | Duration (h) | Oral bioavailability (%) | Comments |
|---|---|---|---|---|---|
| Morphine | 0.1 (2-4 mg every 2-4 h PRN) | 0.3 | 3–4 | 20–40 |
|
|
1.0 | N/A | 3–4 | 60–80 |
|
| Hydromorphone (Dilaudid) | 0.01–0.02 (0.2–0.5 mg every 2-4 h PRN) | 0.05 | 3–4 | 50–70 |
|
|
0.001 (25–50 mcg every 5–15 min in monitored setting) | N/A | 0.5–1 |
|
|
| Codeine | N/A | 1.2 (15–60 mg every 4–6 h PRN) | 3–4 | 40–70 |
|
|
N/A | 0.1 (15–60 mg every 4–6 h PRN) | 3–4 | 60–80 |
|
|
N/A | 0.1 (5–10 mg every 4–6 h PRN) | 3–4 | 60–80 |
|
DEA, (US) Drug Enforcement Administration; IV, intravenous; MAO, monoamine oxidase; PO, by mouth; PRN, as needed.
Generally, NSAIDs are very efficacious and have a low NNT (number needed to treat) when used in appropriate doses. Data supports the use of NSAIDs for acute pain management following a variety of ambulatory surgical procedures, including plastic and aesthetic surgery. Through a series of meta-analyses, the Cochrane group has demonstrated the analgesic efficacy and safety of single-dose NSAIDs, ketoprofen, ketorolac, and lornoxicam.
NSAID hypersensitivity as well as cross-reactivity between different drugs have been reported. In patients with a reported history of sensitivity to acetylsalicylic acid, administration of NSAIDs should proceed with caution. Coxibs may provide a safer alternative, however, cross-reactivity and hypersensitivity in those allergic to NSAIDs is not guaranteed. Celecoxib has a similar structure to sulfonamides and should not be given to patients with a known sulfa drug allergy. NSAIDs are known to cause gastrointestinal (GI) irritation, and GI bleeding. Platelet function is affected which often results in impaired hemostasis. Furthermore, as a result of prostaglandin inhibition, NSAIDs pose a potential risk for renal insufficiency. Renal insufficiency occurs specifically in the presence of hypovolemia, mostly due to perioperative bleeding or dehydration. Cardiovascular side effects include myocardial infarction, particularly with underlying ischemic heart disease. This side effect differs between drugs, with diclofenac posing the greatest risk, and naproxen the least.
Contraindications for NSAIDs, both relative and absolute, are numerous, and discretion must be used in patients with comorbid conditions. However, they remain very effective adjuncts to perioperative pain management, and they reduce the contribution of opioids to postoperative pain. In fact, some studies suggest that NSAIDs may be equianalgesic to opioids for postoperative pain relief. Their routine use in plastic surgery procedures remains controversial due to the potential risk of bleeding and hematoma. There are several studies in both cosmetic and reconstructive patients that have demonstrated no increased risk of hematoma formation with either ibuprofen or ketorolac. Some of these studies are well-designed prospective, blinded studies and meta-analysis.
COX-2 receptor inhibitors
Selective COX-2 inhibitors were developed in an effort to reduce the GI side effects and bleeding associated with NSAIDs. Coxibs reduce, but do not eliminate the risk for GI bleeding. They are effective in the management of postoperative pain and have a low NNT, but their analgesic effect has not been proven to be superior to traditional NSAIDs. A major advantage of Coxibs is their negligible effect on platelet function. The risk of bleeding or hematoma formation is negligible.
The long-term use of Coxibs is associated with potential risk for cardiovascular and thromboembolic events. Due to the risk of perioperative myocardial infarction, Coxibs should be avoided in patients with ischemic heart disease. There is no difference in the incidence of renal side effects between NSAIDs and Coxibs. Overall, Coxibs have a lower risk for bleeding complications due to a negligible effect on platelet function, and a lower risk of GI ulcers and bleeding compared to NSAIDs.
Acetaminophen, NSAIDs, and Coxibs are effective agents in multimodal perioperative pain management. Acetaminophen has minimal effect on platelet function and can be used safely without any such risk for bleeding or hematoma. It can be administered intravenously and can reduce the need for opioid analgesics. NSAIDs and Coxibs are effective analgesics and demonstrate an additive effect when combined with acetaminophen. While NSAIDs affect platelet function and theoretically increase the risk for bleeding and hematoma, Coxibs have minimal risk for bleeding and hematoma formation as well as a lower risk for GI side effects. However, the risk for thromboembolic side effects prevents their use in patients with ischemic heart disease or a history of thrombotic events. Acetaminophen and NSAID/Coxib agents in the perioperative period are well established in clinical practice. The exact regimen can be tailored for each individual patient based on risk/side-effect profile of these agents. In combination with other non-opioid analgesics, these drugs can be very effective in pain management in plastic surgery. Multimodal therapy significantly reduces opioid use, opioid-related side effects, and enhances analgesia. Some centers are even reporting opioid-free surgery.
NMDA-receptor antagonists and gabapentinoids
Ketamine
Ketamine works as a noncompetitive N -methyl-D-aspartate (NMDA)-receptor antagonist. The NMDA receptor is activated with sustained and intense pain stimuli, and has been implicated in both immediate hyperalgesia and long-term changes in pain perception that may lead to chronic postsurgical pain (CPSP). Ketamine has also been shown to downregulate proinflammatory pathways, which may be the mechanisms responsible for antihyperalgesia effects.
Ketamine has a half-life of 180 minutes and is metabolized in the liver, and its unique characteristics include the preservation of respiratory drive and hemodynamic stability. The favorable profile of ketamine as an anesthetic agent includes continuous spontaneous breathing as it has minimal respiratory depressant effects and preserves upper airway muscle, pharyngeal, and laryngeal tone. Further favorable characteristics include a mild sympathomimetic effect that results from catecholamine release, and an inhibition of noradrenaline reuptake leading to an increase in heart rate, stroke volume, and mean arterial pressures. This profile is favorable in hemodynamically unstable patients.
Recent data has demonstrated that ketamine improves analgesia and reduces opioid requirements in the perioperative setting. Furthermore, evidence supports the intraoperative use of ketamine in patients with chronic pain and those on chronic high-dose opioids. Reports demonstrate reduced postoperative pain, as well as reduced opioid consumption. The use of ketamine has also been associated with a significant reduction of opioid-related side effects, including postoperative nausea and vomiting (PONV). Dose-dependent neuropsychiatric effects, including dysphoria, hallucinations, vivid, unpleasant dreams, and catatonia or psychoses, are potential side effects of ketamine, rendering it unfavorable as a sole analgesic agent. However, subanesthetic doses have a considerably lower incidence of these adverse effects and seem to be well tolerated.
There is a lack of data with regard to the use of ketamine in plastic surgery patients, however, many conclusions can be extrapolated from the literature and other patient populations. Low-dose ketamine as an adjunct is most beneficial in surgeries where postoperative pain is expected to be high. The sympathomimetic effects in conjunction with decreased intraoperative and postoperative opioid requirements may help to preserve hemodynamic stability and decrease the need for perioperative vasopressor use. Decreasing the need for perioperative vasopressor use would be ideal for flap perfusion.
At subanesthetic doses (0.1 mg/kg/h), ketamine improves analgesia and reduces opioid requirements. This effect seems most significant for patients with chronic exposure to opioids (tolerance) and for surgeries that are expected to be painful and have a moderate to high degree of pain. Furthermore, the sympathomimetic effects may be beneficial in maintaining hemodynamic stability. Psychiatric side effects such as dysphoria and hallucinations seem to be far less common than with anesthetic doses of ketamine (1–5 mg/kg), and are reported by multiple authors to be well tolerated.
Gabapentinoids
Gabapentin and pregabalin are alkylated analogues of gamma-aminobutyric acid (GABA). Gabapentin was originally developed as an anticonvulsant. Neither of these agents exerts their clinical effects by way of the GABA-A or GABA-B receptors. Instead, they seem to bind voltage-gated calcium channels of cortical and dorsal horn neurons, attenuating the release of the neuropeptides glutamate, norepinephrine, and substance P . Furthermore, gabapentin may activate descending inhibitory noradrenergic pathways that regulate the neurotransmission of pain signals in the dorsal horn.
Gabapentin has been used successfully in several neuropathic pain states, including complex regional pain syndrome, multiple sclerosis, and postherpetic neuralgia. Pregabalin has also been found to be useful in diabetic neuropathy. Both agents are available only as oral preparations and differ in bioavailability.
Several studies have concluded that both gabapentin and pregabalin reduce both postoperative pain and opioid use postoperatively. Overall the gabapentinoids are well tolerated, with the most common transient adverse effects of somnolence, dizziness, headaches, balance problems, peripheral edema, sweating, dry mouth, and nausea and vomiting.
When gabapentinoids (neurontin and pregabalin) are combined with other central nervous system depressants (benzodiazepines and opioids), respiratory depression can occur in the elderly and in patients with pre-existing respiratory diseases like chronic obstructive pulmonary disease (COPD). Patients who are on chronic opioids are also more likely to die from respiratory depression if gabapentin is co-administered. The FDA placed a “Black Box” warning on gabapentin in December 2019 for these reasons ( https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin ). There is some evidence that these adverse events are dose-related. Lower doses and short-term perioperative administration may still raise the same concerns of respiratory complications (pneumonia, respiratory depression, re-intubation) without reducing opioid consumption or length of stay. In pediatric patients, while there is evidence that gabapentin reduces opioid use postoperatively, the data is sparse and it is difficult to make strong recommendations to use prophylactic perioperative gabapentinoids. In fact, this is the current case for both pediatric and adult patients.
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