Progress in surgical acute pain management has allowed most foot and ankle surgery to be performed in ambulatory outpatient surgical centers. Multimodal analgesia focuses on improving postoperative pain by combining pharmacologic and other modalities, addressing multiple pain mechanisms and receptor pathways while reducing adverse effects through lower doses of oral medications. Local anesthesia techniques provide excellent pain relief with few adverse events. Multimodal analgesia in foot and ankle surgery provides superior pain relief, and reduced opioid dependence and opioid-related side effects, improving patient satisfaction, safety, and timely return to function.
Key points
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Recent advances in multimodal analgesia have allowed most foot and ankle surgery to be performed in ambulatory outpatient surgical centers.
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Multimodal analgesia focuses on improving postoperative pain while limiting adverse effects of individual agents, which allows less reliance on opioid pain medications and a decrease in their adverse effects.
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Numerous oral pain medications have been used in multimodal therapy, including nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors, acetaminophen or paracetamol, neuromodulatory medications (gabapentin and pregabalin), opioid agonists, glucocorticoids, and N-Methyl d -Aspartate (NMDA) antagonists.
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Local anesthesia techniques, including wound infiltration and intra-articular injections, provide excellent pain relief with very few adverse events.
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The combination of local anesthetic techniques or peripheral nerve blocks with supplementation using oral agents should be first-line analgesic therapy for patients undergoing outpatient foot and ankle procedures.
Overview
There has been a growing interest in alternative therapies for pain management following orthopedic procedures. In the past, opioid pain medications have been relied on as the treatment of choice for postoperative pain control. Recent progress in surgical and acute pain management strategies have allowed for most patients undergoing foot and ankle surgery to be performed on in ambulatory outpatient surgical centers. This article reviews multimodal analgesia options in the setting of perioperative foot and ankle surgery.
There are more than 90 million orthopedic procedures performed each year in the United States. Of these procedures, 35 million are performed in ambulatory centers. Orthopedic patients report the highest incidence of pain compared with other types of surgical procedures, with greater than 50% of patients having suboptimal pain control. Postoperative pain is the most important concern among patients and is the most common reason for fear and avoidance of surgery.
Overview
There has been a growing interest in alternative therapies for pain management following orthopedic procedures. In the past, opioid pain medications have been relied on as the treatment of choice for postoperative pain control. Recent progress in surgical and acute pain management strategies have allowed for most patients undergoing foot and ankle surgery to be performed on in ambulatory outpatient surgical centers. This article reviews multimodal analgesia options in the setting of perioperative foot and ankle surgery.
There are more than 90 million orthopedic procedures performed each year in the United States. Of these procedures, 35 million are performed in ambulatory centers. Orthopedic patients report the highest incidence of pain compared with other types of surgical procedures, with greater than 50% of patients having suboptimal pain control. Postoperative pain is the most important concern among patients and is the most common reason for fear and avoidance of surgery.
Perioperative surgical home
Pain management is a multifaceted system involving patients, physicians, hospitals, and health care organizations. The concept of a perioperative surgical home involves collaboration between the patient, the orthopedic surgeon, the anesthesiologist, and primary care or internal medicine provider. The perioperative surgical home provides a continuum of patient-focused perioperative care in the preoperative, intraoperative, and postoperative periods to allow for preoperative optimization, safe intraoperative care, and smooth transitions postoperatively through rehabilitation and back to primary care. The goal of this system is to improve outcomes following orthopedic surgery. Communication among these team members is essential to produce good perioperative outcomes and transitions after surgery. There are increased complications associated with increased postoperative pain. Prolonged hospitalization, increased readmission rate, higher costs, and slower recovery are associated with poorer postoperative pain control. Management of patient expectations for the preoperative, perioperative, and postoperative course in regard to rehabilitation and pain are key in improving outcomes following surgery. Multimodal analgesia is an important component in this pain management system.
Opioid epidemic
Traditionally, opioid analgesics have been the cornerstone of postoperative analgesia following orthopedic surgery. Opioids as the sole source of analgesia are associated with significant side effects, and opioid-related adverse events occur more frequently with increased age, obesity, chronic obstructive pulmonary disease, obstructive sleep apnea, and hepatic and renal impairment. A retrospective review of a large national hospital database of 319,898 surgeries showed a 12.2% rate of opioid-related adverse events. Patients who experienced opioid-related adverse events had a higher adjusted mean cost of hospitalization, a greater length of stay, and were more likely to be readmitted. Hospitalizations and emergency department visits due to opioid abuse and misuse continue to increase. Between 2002 and 2012, hospitalization rates for opioid overuse among adults 18 years or older increased by greater than 60%. From 2006 to 2010, emergency department visits involving nonmedical use of opioids increased by 112%. Since 2003, opioid analgesics have been the cause of more deaths from overdose than cocaine and heroine combined. The increase in abuse, accidental death, and the high health care costs associated with opioid abuse has put an emphasis on alternative methods for perioperative pain control, as well as legislation aimed at restricting opioid prescriptions.
Multimodal analgesia
Recent gains in the area of multimodal analgesia have led to effective alternative methods of pain control. Multimodal analgesia focuses on improving postoperative pain while limiting adverse effects of individual agents. Combining pharmacologic and other modalities addresses multiple pain mechanisms while reducing adverse effects through the use of lower doses of individual modalities. Multimodal therapy can shorten hospital stays, minimize use of narcotics, decrease pain scores, reduce opioid adverse effects, decrease times to reach rehabilitation milestones, and improve patient outcomes. Effective pain control requires combined drug synergy effects that block generation and perception of pain at several different stages in the pain pathway. Neuraxial and regional anesthesia block transmission of noxious stimuli in sensory neurons before it starts, and multimodal analgesia potentiates the effect of concomitant medications. The simultaneous use of 2 or more analgesics that act at different sites and receptor pathways within the central and peripheral nervous systems work to reduce pain and minimize opioid use ( Fig. 1 ). Various oral medications have been used in multimodal therapy, including nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 inhibitors, acetaminophen or paracetamol, neuromodulatory medications (gabapentin and pregabalin), opioid agonists, steroids, and N-methyl d -aspartate (NMDA) antagonists.
There is limited literature in foot and ankle surgery regarding the use of multimodal pain regimens. A multimodal pain protocol suggested by Michelson and colleagues seems to have favorable outcomes in patients undergoing ankle and hindfoot fusions. This multimodal pain protocol consisted of preoperative oral administration of extended-release oxycodone (10 mg), celecoxib (200 mg), pregabalin (75 mg), acetaminophen (1gm), and prednisone (40 mg). The postoperative pain regimen included oral extended-release oxycodone (10 mg every 12 hours), celecoxib (200 mg every 12 hours), and acetaminophen (1000 mg every 6 hours). Short-acting oxycodone (5–20 mg every 4 hours) was provided for breakthrough pain. Subjects were then discharged with prescriptions for 2 days of long-acting oxycodone, 2 weeks of celecoxib, and 2 weeks of short-acting oxycodone. The traditional protocol included no preoperative medications and the use of a patient-controlled analgesia–delivered parenteral opioid (dilaudid or morphine). The choice of the pain control protocol was based on surgeon preference. In this retrospective review, 175 subjects received the multimodal postoperative analgesia protocol, and 45 subjects received the traditional pain management. The multimodal protocol subjects had significantly shorter length of hospital stays, controlling for complexity of the surgery performed. Multimodal analgesia works to limit the adverse effects of opioids, improve postoperative pain, and decrease length of hospital stay.
Components of multimodal analgesia
Nonsteroidal Anti-inflammatory Drugs
NSAIDs are commonly used medications to treat pain and inflammation ( Table 1 ). The mechanism of action for this class of drugs is to inhibit the enzyme COX, which blocks the production of prostaglandins. Two isoenzymes of cyclooxygensase have been identified: COX-1 and COX-2. The COX-2 isoenzyme is involved primarily in the production of prostaglandins that lead to the inflammatory response and pain perception. The COX-1 isoenzyme has multiple physiologic roles, including platelet, kidney, and gastrointestinal tract functions. Nonspecific NSAIDs are effective for relieving pain and inflammation with the inhibition of the COX-2 isoenzyme, but they are also associated with platelet dysfunction, gastrointestinal and renal toxicity, increasing cardiovascular event risk, and the potential for impaired bone and tendon healing.
| Drug Category | Mechanism of Action | Dosing | Advantages | Disadvantages |
|---|---|---|---|---|
| NSAIDs | ||||
| Ibuprofen (PO) | COX inhibitor (nonspecific) | 400–800 mg q 6 h | No addictive potential, OTC, efficacious analgesic | Potential renal toxicity, platelet inhibition, inhibition of bone & soft tissue healing, gastric mucosa effects |
| Ketorolac (IV) | 15–30 mg q 6 h (limit to 6 doses total) | Potent analgesic | Cardiovascular risk, gastric mucosa effects, higher gastric mucosa toxicity compared with other NSAIDs | |
| Celexicob | COX-2 inhibitor (specific) | 200 mg q 12 h | Reduced platelet effect, reduced gastric toxicity | Increased cardiovascular risk, potential renal toxicity |
| Acetaminophen | CNS inhibition of COX, modulation of central serotonin | Well tolerated | Caution with hepatic disease | |
| Acetaminophen (PO) | Up to 1 g q 6 h | Inexpensive | May not produce therapeutic levels in perioperative period | |
| Paracetamol (IV) | Up to 1 g q 6 h | Reliable CNS levels in perioperative period | Expensive | |
| Neuromodulatory Medications | Voltage-dependent calcium channels in CNS or PNS | Reduces opioid use & opioid-related side effects | ||
| Gabapentin (PO) | 300 mg tid | Dizziness, drowsiness, ataxia, fatigue | ||
| Pregabalin (PO) | 75–100 mg q 12 h | Dizziness, somnolence, visual disturbances | ||
| Opioid Agonist | Constipation, nausea, pruiritis, respiratory depression | |||
| Oxycodone (PO) | Mu receptor agonist | 5–15 mg q 3-6 h | ||
| Combined Opioid Agonist or Norepinephrine- SSRIs | Mu agonist or inhibitor of norepine phrine-serotonin reuptake | Caution use with other SSRIs such as SSRI antidepressants | ||
| Tramadol (PO) | Serotonin & norepinephrine uptake inhibitor | 50–100 mg q 6 h | Lower risk of tolerance, dependence | Flushing, dizziness, headache, drowsiness, insomnia |
| Tapentadol (PO) | Norepinephrine reuptake inhibitor only | 50–75 mg q 6 h | Lower risk of tolerance, dependence, nausea, constipation | Dizziness, drowsiness, fatigue, insomnia |
| Glucocorticoids | ||||
| Dexamethasone (PO) | 0.1 mg/kg dose preoperative or postoperative | Decrease nausea, decrease opioid use | Cardiovascular risk, CNS effects, decreased glucose tolerance | |
| NMDA Antagonist | Modulate central sensitization of nociceptive stimulation | |||
| Ketamine (IV) | 0.5 mg/kg initial bolus, 0.1 mg/kg/h infusion intraoperative, can continue same dose postoperative for 48 h | Less opioid requirements postoperative | Agitation, confusion, hallucinations, muscle tremors, HTN, high abuse potential | |
| Memantine (PO) | Start at 5–10 mg bid, titrate up weekly to 30 mg/d | Well tolerated | Psychosis | |
Two randomized, controlled trials looking at the use of postoperative diclofenac (nonselective COX) versus placebo in subjects who underwent foot and ankle surgery found that the diclofenac groups in both studies had significantly decreased postoperative pain for 5 days after surgery. The medications were well tolerated in both studies with high subject satisfaction and decreased need for supplemental narcotic analgesia compared with the placebo group.
The COX-2-specific NSAIDs, referred to as coxibs, have been developed to reduce or eliminate many unwanted side effects of nonselective NSAIDs, specifically the gastrointestinal and platelet effects. Previous coxibs, including rofecoxib and valdecoxib, have been removed from the market due to concerns that they are associated with increased cardiovascular risk. Selective COX-2 inhibitors have been found to be quite effective in postoperative pain control in patients undergoing orthopedic procedures. Brattwall and colleagues conducted a trial comparing postoperative etoricoxib versus tramadol in subjects undergoing bunion surgery. The etoricoxib group had significantly decreased pain scores, increased satisfaction, and decreased side effects compared with the tramadol group.
The use of NSAIDs and selective COX-2 inhibitors in orthopedic surgery remains controversial. There have been numerous studies suggesting the inhibitory effects of NSAIDs on bone healing in animal models, but no definitive research to date has shown evidence of an actual effect in humans. More recent literature has started to examine if NSAIDs and coxibs have an impact on soft tissue healing. A recent systematic review found that short-term, low-dose use of NSAIDs and COX-2 inhibitors do not seem to have detrimental effects on soft tissue healing but may show an inhibitory effect in bony healing. Based on the available literature, the investigators recommended the use of NSAIDs and coxibs for soft tissue procedures, but recommended against their use in procedures requiring bone healing.
Acetaminophen and Paracetamol
Oral acetaminophen and paracetamol, its parenteral form, are well-tolerated agents with relatively few side effects that are commonly used in conjunction with opioids for postoperative pain control. The mechanism of action for these agents is not well understood, but they have been shown to inhibit COX in the central nervous system (CNS) and have an effect on central modulation of the serotonin system. There seems to be little difference in analgesia effects between the oral and parenteral forms of acetaminophen when therapeutic levels are maintained. A randomized, controlled trial of 30 subjects undergoing knee arthroscopy showed that all subjects who received parenteral acetaminophen reached plasma levels in the therapeutic analgesic range. In comparison, less than half of the subjects who received the oral form of the medication received therapeutic analgesic plasma levels. The subjects who received intravenous paracetamol showed a trend toward decreased need for rescue analgesia and a shorter stay in the recovery room.
Neuromodulatory Medications (Gabapentin, Pregabalin)
Gabapentin and pregabalin are gamma-aminobutyric acid analogues that bind to voltage-gated calcium channels in the central and peripheral nervous system and alter the release of excitatory neurotransmitters. Pregabalin has a faster onset, more predictable plasma concentrations, and fewer side effects compared with gabapentin. Peak plasma concentrations are reached within an hour for pregabalin due to its absorption kinetics in the gut versus 3 to 4 hours for gabapentin, which is absorbed by a saturable receptor-mediated route. As a result, gabapentin has less reliable bioavailability than pregabalin. Pregabalin is more expensive than gabapentin, but for a brief course in the perioperative period it can often be covered. The most common side effects associated with pregabalin are dizziness, visual disturbances, and somnolence. As an adjunct for pain control, the typical starting dose is 75 mg 2 times per day, although effective doses for reducing perioperative opioid requirements range up to 150 mg 2 times per day. Pregabalin has been found to reduce opioid requirements and opioid-related side effects in multiple perioperative settings and procedures. Subjects treated with pregabalin in the perioperative period have shown a lower incidence of chronic pain associated with surgery. A randomized, placebo-controlled, double-blind study of 240 subjects undergoing total knee arthroplasty found that the 120 subjects who received perioperative pregabalin showed significantly lower rates of neuropathic pain, less opioid consumption, and improved functional rehabilitation compared with the placebo group at 6 months after surgery.
Opioid Agonists (Tramadol and Tapentadol)
Opioid medications work through agonistic activity at the mu opioid receptor within the CNS. Opioids remain the mainstay analgesic prescribed by most clinicians despite their addictive potential and side-effect profile. The most common opioid-related side effects include nausea, constipation, pruritus, and ventilatory depression. All opioid medications seem to have similar side-effect profiles and analgesic effects when compared in equivalent doses. Multimodal analgesia allows for a reduction in opioid dose requirements and thus opioid-related side effects. In subjects undergoing corrective bunion surgery, Richards and colleagues found that those subjects randomized to receive a combination of oral immediate-release morphine and oxycodone had significantly decreased pain and side effects compared with subjects who received higher doses of individual oral doses of morphine or oxycodone.
Tramadol and tapentdaol are medications with a mechanism of action at both the opioid receptor and via monoamine reuptake inhibition. Tramadol inhibits the reuptake of both serotonin and norepinephrine; tapentadol only affects norepinephrine levels. These medications do not rely on mu opioid agonist activity as their sole mechanism for analgesia. There is evidence to suggest that these analgesics may be associated with less respiratory depression than conventional opioids at similar levels of dosing. Tapentadol has a lower incidence of gastrointestinal side effects, including nausea, vomiting, and constipation, compared with other commonly prescribed opioids. Tramadol has not been associated with the same decrease in gastrointestinal side effects as tapentadol. Care must be taken in prescribing these medications with drugs whose mechanism of action also involve increasing CNS serotonin and norepinephrine levels, such as commonly prescribed serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Serotonin syndrome is a potentially life-threatening condition that may develop in patients with increased CNS serotonin or norepinephrine concentrations. Agitation, delirium, and autonomic dysfunction, including diaphoresis, tachycardia, hyperthermia, as well as neuromuscular hyperactivity manifesting as muscle rigidity and myoclonus, are the main clinical findings in patients presenting with serotonin syndrome.
Stegmann and colleagues conducted a randomized, double-blind, controlled trial of immediate-release tapentadol versus immediate-release oxycodone versus placebo in subjects undergoing a first metatarsal osteotomy. The subjects randomized to the tapentadol and oxycodone groups had significantly less pain postoperatively compared with the placebo group at comparable rates. The subjects taking tapentadol had lower rates of nausea, dizziness, vomiting, and constipation compared with the subjects taking oxycodone. There is evidence to suggest that tapentadol shows comparable analgesia to oxycodone with fewer side effects in patients undergoing foot surgery.
Glucocorticoids
Glucocorticoid administration, in the perioperative period, is reported to reduce pain, shorten hospital stay, and decrease time back to work following both inpatient and outpatient orthopedic surgeries. Single-dose preoperative or 24-hour perioperative use of high-dose glucocorticoids has been shown to be safe without evidence of increased risk for postoperative wound infections or other complications. Preoperative administration of intramuscular betamethasone improved pain relief during the first 24 hours postoperatively in a study of orthopedic day-surgery subjects. A randomized, controlled trial of 50 subjects undergoing first metatarsal osteotomy, as a day-surgery procedure, were randomized to receive either 9 mg oral dexamethasone or placebo preoperatively and 24 hours postoperatively. The investigators found significantly lower pain scores, less nausea, and significantly less oxycodone consumption in the dexamethasone group in the acute postoperative period.
N-Methyl D-Aspartate Antagonists (Ketamine and Memantine)
Ketamine is an NMDA antagonist with analgesic properties that modulate central sensitization of nociceptive stimulation. NMDA receptors are involved in the perception of postoperative pain due to their role in neuronal plasticity leading to central sensitization. Ketamine is administered intravenously with an initial bolus of 0.5 mg/kg, followed by continuous infusion of 3 μg/kg/min during surgery, and 1.5 μg/kg/min for the following 48 hours. When used in combination with peripheral nerve blocks, several trials have shown that subjects undergoing total knee arthroplasty and knee arthroscopy require significantly less morphine than the control groups who only received peripheral nerve blocks. Ketamine is associated with agitation, confusion, hallucinations, muscle tremors, hypertension, and thus its use should be monitored closely. Memantine is an orally available noncompetitive NMDA receptor antagonist used to treat moderate to severe Alzheimer dementia. It has also been found to be an effective analgesic and may prove to be more useful than ketamine as an analgesia adjunct in decreasing the risk for the development of postoperative chronic pain.
Combination Therapies
Combination therapies of acetaminophen (or paracetamol) and NSAIDs are effective analgesia options in subjects undergoing orthopedic procedures. A systematic review of the literature, including 21 studies, showed that the combination of paracetamol and an NSAID, including ibuprofen, diclofenac, aspirin, tenoxicam, rofecoxib, ketoprofen, and ketorolac, had improved analgesia as compared with either medication alone in surgical subjects.
Although limited in data, the combination of gabapentin plus celexicob on postoperative pain after orthopedic procedures has been found to be an effective treatment therapy. A randomized, double-blind, controlled trial of 114 subjects who underwent elective laminectomy were assigned to gabapentin alone (900 mg daily), gabapentin (300 mg 2 times per day) plus celexicob (200 mg 2 times per day), or placebo. Subjects who received the combination therapy gabapentin plus celexicob had significantly lower mean pain severity scores and morphine consumption for 24 hours postoperatively than the gabapentin alone or the placebo groups. These subjects also had significantly higher postoperative satisfaction. The gabapentin-only group experienced significantly more drowsiness than the other 2 groups.
Intra-articular Injections
Intra-articular injection of local anesthetics is commonly used for pain relief after arthroscopy in orthopedic procedures. The use of a 1-time intra-articular injection of bupivacaine, morphine, and methylprednisolone after ankle arthroscopy has been shown to decrease postoperative pain and reduction in impairment. Intra-articular injections of bupivacaine following knee and ankle arthroscopic procedures have been shown to be safe and effective in decreasing postoperative pain scores and additional analgesic requirements.
Local Wound Infiltration
Local wound infiltration with local anesthetic or a multidrug injection is a convenient, safe, and effective option for pain control. It has been widely used after total knee and hip arthroplasties. It seems to have favorable outcomes in the foot and ankle literature, as well as in the few studies looking at the effect of local wound infiltration on postoperative pain and outcomes. Kim and colleagues injected ropivacaine, morphine, ketorolac, and epinephrine in the wounds of subjects undergoing bilateral hallux valgus correction surgery. The contralateral side was injected with normal saline. Subjects reported significantly less pain on the local injection side compared with the contralateral side. Similar results were found in a study of subjects undergoing ankle supramalleolar osteotomies. Thirty-one subjects were randomized to receive a local wound injection of ropivacaine, morphine, ketorolac, and epinephrine before wound closure. Subjects receiving this injection reported significantly less postoperative pain and had decreased opioid requirements compared with the placebo group.
Liposomal bupivacaine is a local anesthetic that allows for extended, sustained release of bupivacaine over 72 hours without reaching systemically toxic levels. It is approved by the US Food and Drug Administration for single-dose infiltration into the surgical site to produce postsurgical analgesia. In a case-control study by Robbins and colleagues, local liposomal bupivacaine was injected into the wounds of 20 subjects undergoing forefoot surgery at the time of closure. These subjects showed a trend toward lower postoperative pain scores and fewer pain medication refills compared with the control group. Both groups received a standard multimodal analgesic regimen, including celocoxib, preoperatively and postoperatively, and oral narcotics. Additionally, there was no significant difference between the groups for wound infection. Golf and colleagues conducted a randomized, placebo-controlled trial of liposomal bupivacaine versus placebo in 193 subjects undergoing bunion surgery. Before closure, wound infiltration of liposomal bupivacaine was administered. The 97 subjects treated with liposomal bupivacaine had significantly less pain than the control group postoperatively. In addition, more subjects in the extended-release bupivacaine group avoided the use of opioid rescue medication during the first 24 hours and were pain-free up to 48 hours after surgery. Liposomal bupivacaine has been shown to be an effective adjunct to multimodal postoperative pain regimens in many other orthopedic procedures. In addition, it has been associated with decreased postoperative narcotic requirements, shorter inpatient length of stay, and lower inpatient costs. No studies have shown an effect on wound healing or union when compared to plain bupivacaine or a placebo.
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