At 8 AM, MG, a 47-year old Hispanic man, arrives by ambulance at a level II trauma center ED, having been involved in a multivehicle accident. (This case is a composite based on our clinical experience.) MG is alert, oriented, and able to communicate. He is immediately taken to the trauma bay for triage. He reports pain, which he rates as a 9 on a 0-to-10-point pain scale, in his left upper arm and shoulder, lateral chest area, and anterior lower leg. He has a heart rate of 134 beats per minute, his blood pressure is 160/100 mmHg, and his respirations are shallow at a rate of 30 breaths per minute. He is obese, with a body mass index of 36.9 kg/m2, and has no known drug allergies. The ED nurse promptly medicates him for pain with IV fentanyl 100 mcg given over one minute, delivers oxygen by nasal cannula at a rate of 4 L/min, initiates cardiac monitoring and continuous pulse oximetry, and draws blood for hematologic and chemistry profiles.
When removing his trousers, the nurse sees that his left tibia is protruding through the skin and applies a sterile pressure dressing to minimize bleeding and reduce risk of infection. Stat X-rays of the painful areas reveal a closed fracture of the upper left humerus, two left rib fractures, and an extensive compound left tibial fracture. Both injured extremities are immobilized with splints. The nurse accompanies MG to radiology for computed tomography scans of the head, cervical spine, chest, abdomen, and pelvis, which show no additional traumatic injuries.
After MG is returned to the ED, his wife arrives and informs the ED nurses that her husband takes nebivolol 10 mg once a day for poorly controlled hypertension and that his primary care physician has recently expressed concern about his kidneys. Since he was diagnosed with obstructive sleep apnea two years ago, MG has used a continuous positive airway pressure (CPAP) device for sleep. MG's wife accompanies him to the preoperative holding area where he is prepared for surgery to stabilize his fractured tibia.
The trauma team, preoperative nurse, and certified registered nurse anesthetist (CRNA) agree to start multimodal analgesia prior to surgery. MG's nurse cautions that his blood test shows a mildly elevated serum creatinine level of 2.1 mg/dL, which raises concerns about giving him a nonsteroidal antiinflammatory drug (NSAID), such as IV ketorolac or ibuprofen. The team decides to administer IV acetaminophen 1,000 mg and IV fentanyl 75 mcg. MG's CRNA performs a left femoral nerve block, injecting 15 mL of the local anesthetic ropivacaine 0.5%. MG now rates his pain as a 4 on a 0-to-10-point pain scale. His heart rate is 90 beats per minute, his respiratory rate is 22 breaths per minute, and his blood pressure is 130/90 mm/Hg.
Multimodal analgesia or “balanced analgesia” combines analgesics from two or more drug classes or analgesic techniques that employ different mechanisms of action, targeting different (peripheral or central) pain pathways, thus achieving a synergistic effect at lower analgesic doses.1, 2 This article reviews various multimodal analgesic interventions for acute pain, discusses their benefits, and summarizes expert consensus recommendations and evidence-based practices for using multimodal therapy.
HOW MULTIMODAL ANALGESIA WORKS
Multimodal analgesia may employ the following pharmacologic approaches3:
- analgesics, including opioids, nonopioid analgesics (such as acetaminophen and NSAIDs), the gabapentinoids (gabapentin and pregabalin), serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and N-methyl-D-aspartate (NMDA) receptor antagonists
- neuraxial (epidural and intrathecal) interventions
- peripheral nerve block interventions
- intraarticular and wound infiltration with local analgesia
Physical and behavioral health interventions are also a part of multimodal analgesic strategies. Introduced more than two decades ago,2 multimodal analgesia is currently recommended for treating both acute1, 3 and chronic4 pain. The synergy created when multimodal regimens are used to target discrete components of the peripheral and central pain pathways provides effective analgesia at lower opioid dosing, reducing related risk and producing fewer adverse effects (see Figure 1).5-8
Each phase of the nociceptive pain process may be targeted by some type of analgesic:
- Transduction, in which activated nociceptors (the free nerve endings of primary afferent neurons that sense noxious stimuli) release an electric signal, may be disrupted by NSAIDs and membrane stabilizing agents, such as gabapentinoids.
- Transmission, in which the electric signal moves from the site of injury to the spinal cord and brain, may be interrupted by local anesthetics and gabapentinoids.
- Perception, the awareness of pain in the somatosensory cortex of the brain, may be moderated by systemic opioids and NMDA receptor antagonists.
- Descending and local modulation, the adaptive processes through which pain impulses may be enhanced or diminished either centrally (by descending pathways that originate in the brain and project to the spinal cord) or in the periphery, are responsive to such interventions as neuraxial therapy, peripheral nerve blocks, and local infiltration analgesia.
Because of their opioid-sparing effects, multimodal strategies are particularly useful and often indicated for patients who are opioid dependent or opioid tolerant.9 Multimodal analgesic plans of care should be individualized to the
- type of pain.
- mechanism of pain (inflammatory or neuropathic).
- type of surgical procedure.
- location of pain.
- expected duration of pain.
PREVENTIVE MULTIMODAL ANALGESIA
The timing of multimodal analgesia is an important consideration in its use. After consulting the surgical team and clinical nurses, MG's CRNA administers IV acetaminophen and fentanyl and performs a femoral nerve block prior to surgery. This preoperative analgesic strategy is part of MG's “preventive analgesia.” Traditionally, preoperative analgesia has been called “preemptive analgesia,” but Dahl and Kehlet contend that the term “preventive” better explains the assumption on which the practice is based—“that the only way to prevent central sensitization might be to completely block any pain and afferent signals from the surgical wound from the time of incision until final wound healing.”10 Preventing the likelihood of central sensitization is important because, in theory, it reduces the likelihood of chronic postsurgical pain syndrome (discussed in “Assessing and Managing Acute Pain: A Call to Action,” on page S4).
There is evidence that the efficacy of systemic multimodal regimens is procedure-specific.11 In their extensive review, Pozek and colleagues conclude that when multimodal approaches do not prevent central sensitization, it may be because of inadequate duration, as these therapies are often administered only intraoperatively and not continued throughout the postoperative period required for healing and recovery.12 Nurses must ensure that patients receiving multimodal analgesia have a plan in place to manage pain effectively during hospitalization and following discharge.
MG's plan for preventive multimodal analgesia. With preoperative multimodal analgesia initiated, MG's team discusses plans for his postoperative pain control during surgery. He'll receive systemic therapy with opioid analgesics, a nonopioid (acetaminophen), and a gabapentinoid (gabapentin) to manage his postoperative pain and pain from his left humerus and rib fractures. A femoral nerve catheter will deliver a continuous infusion of the local anesthetic ropivacaine, providing a peripheral nerve block to alleviate pain from his tibial fracture surgery. Compared with bupivacaine, ropivacaine provides optimal continuous regional analgesia for preoperative, intraoperative, and postoperative pain control while producing a lower incidence and degree of motor blockade.13 The team debates whether an NSAID should be added to MG's regimen, given the nature of his bone pain, but ultimately decides against that strategy on account of his mild renal impairment.
MG's initial pain management plan includes the following:
- IV hydromorphone 0.2 mg demand dose by patient-controlled analgesia (PCA) with a lock-out interval of 10 minutes (up to 1.2 mg per hour) to start immediately after surgery
- IV acetaminophen 1,000 mg every six hours for 24 hours to start immediately after surgery, then acetaminophen 650 mg by mouth every four hours
- gabapentin 200 mg by mouth every eight hours to start as soon as MG can tolerate sips of water
- ropivacaine 0.2% by continuous infusion through a left femoral nerve catheter at 6 mL per hour for up to 36 hours
- IV ondansetron 4 mg every four to eight hours for nausea and vomiting
- docusate sodium 100 mg by mouth twice a day as a stool softener, and senna 15 mg by mouth twice a day for preventing opioid-induced constipation (to be held if the patient has a loose stool or diarrhea)
SYSTEMIC MULTIMODAL ANALGESICS
Nonopioids. For acute pain management in the perioperative setting, the American Society of Anesthesiologists Task Force on Acute Pain Management advocates around-the-clock nonopioid analgesics, unless contraindicated, as first-line agents and as adjuvant agents to opioids.14
NSAIDs, which are indicated for pain from inflammation, are an integral part of multimodal acute pain management. NSAIDS inhibit cyclooxygenase (COX), an enzyme that synthesizes prostaglandins. The two most common forms of COX are COX-1, which synthesizes prostaglandins that are important in such functions as platelet aggregation, gastric cytoprotection, and kidney function, and COX-2, which synthesizes prostaglandins that promote inflammation and pain at sites of injury.15
The extent of enzyme inhibition varies among the NSAIDs. Some are more potent inhibitors of prostaglandin synthesis, while others are more effective at mediating nonprostaglandin effects.16 Patient response to different NSAIDs varies, which suggests that transitioning from one NSAID to another in a different class could provide improved pain relief. Preoperative COX inhibitors (primarily selective COX-2 inhibitors)17 and postoperative nonselective and selective NSAIDs18 have been associated with reduced postoperative opioid consumption. In patients undergoing bowel surgery, administering ketorolac (a nonselective NSAID) in addition to IV morphine by PCA was found to reduce morphine consumption by 18.3% and to speed the return of normal bowel function.19
Adverse events from NSAIDs include platelet inhibition (leading to bleeding), inhibition of prostaglandin formation required for normal gastrointestinal and renal function, cardiotoxicity (selective COX-2 inhibitors), hepatotoxicity, and drug-induced asthmatic responses (nonselective COX inhibitors).15 NSAID toxicity profiles vary; nurses should refer to drug information resources specific to each. In general, NSAIDs should be avoided in patients who have or are at risk for bleeding, gastrointestinal ulceration, cardiovascular events, or renal or hepatic impairment that can significantly affect drug clearance and increase oral bioavailability.1, 20 The benefits of pain relief from NSAIDs must be weighed against risks of adverse effects, including impaired bone healing.21, 22 Evidence supports that ketorolac given in the first 24 hours after surgery does not affect time to healing or incidence of bone nonunion after a fracture.23 While debates exist over whether NSAIDs cause anastomotic leaks after bowel surgery, data indicate that the risk of anastomotic leakage after colorectal surgery is no greater with the use of NSAIDs.24
Acetaminophen. Although acetaminophen's mechanism of action is not well understood, it is believed that its primary analgesic effect is induced by its inhibition of COX, interference with NMDA receptor activation, and promotion of descending inhibitory serotonergic pathways that interfere with spinal nociceptive processing.25 IV acetaminophen is available in the United States, indicated for the treatment of mild to moderate pain and as an adjunct to opioid analgesics for the treatment of moderate to severe pain. For adults and adolescents weighing at least 50 kg (110 lb), recommended IV dosing is 1,000 mg every six hours or 650 mg every four hours, with a maximum single IV dose of 1,000 mg and a minimum dosing interval of four hours. The maximum daily dose of acetaminophen is 4,000 mg per day (including all routes of administration and all acetaminophen-containing products including combination products). A recent Cochrane review that included 75 studies of patients receiving IV acetaminophen (47 studies) or the prodrug form of IV acetaminophen (25 studies) or both (three studies) for postoperative pain showed that 36% of participants overall experienced at least 50% pain relief over four hours compared with 16% of participants receiving placebo.26 In one of the studies reviewed, patients who had undergone either total knee or hip replacement surgery and were given adjuvant IV acetaminophen 1,000 mg at six-hour intervals in addition to opioid therapy reduced opioid consumption by 46% (8 mg morphine equivalent) over the first six hours (P < 0.01) and by 33% (19 mg morphine equivalent) over 24 hours (P < 0.01), compared with patients given opioid therapy and placebo.27 Other than increased bioavailability, the IV formulation of acetaminophen has no clear advantage over the oral form in patients able to take oral medications, as both are effective and have similar safety profiles.28
Smith provides a table of studies showing that IV acetaminophen and NSAIDs are comparable in their analgesic effects.29 Acetaminophen is contraindicated in patients with known hypersensitivity to acetaminophen or its excipients and in patients with severe hepatic impairment or severe active liver disease.
The gabapentinoids, gabapentin and pregabalin, are anticonvulsants, often used orally, that are approved to treat neuropathic pain. They act as membrane stabilizers, presumably by inhibiting the transmission of painful stimuli, and also reduce the potential for central sensitization in the dorsal horn.30 Optimal doses for preoperative and postoperative oral gabapentin and pregabalin have not been determined, with dose ranges varying, respectively, from 300 to 1,200 mg daily and from 50 to 300 mg daily.31 The greater bioavailability of pregabalin makes it easier to titrate to effect for short-term use.
A meta-analysis of 17 randomized controlled trials that included a total of 1,793 inpatients undergoing elective surgery found that, regardless of dose, those receiving preoperative gabapentin (n = 895) within 24 hours of surgery had a significant reduction (P < 0.001) in opioid consumption compared with controls (n = 898).32 This reduction was most pronounced in patients undergoing breast cancer surgery; cholecystectomy; and orthopedic, spinal, or thyroid surgeries. Others have documented 24-hour opioid-sparing effects and decreased pain with perioperative gabapentin for abdominal hysterectomy and spinal surgery.33 Gabapentin 1.2 g per day by mouth, administered one day before and two days after lower limb surgery, also had favorable effects on pain and analgesic consumption when used as an adjunct to epidural analgesia.34 Compared with placebo, when oral pregabalin was administered to patients undergoing total hip arthroplasty at dosages of 150 mg before surgery and 75 mg twice a day after surgery, both during hospitalization and for seven days after discharge as an adjunct to the standard postsurgical regimen (oral celecoxib 200 mg every 12 hours for 72 hours and morphine, followed by an oral opioid–acetaminophen product), 24-hour opioid consumption and pain scores were significantly reduced (P < 0.05) in the first seven days after discharge.35 There were no significant differences in pain scores between the pregabalin- and placebo-treated groups during hospitalization through postoperative day 4.
The NMDA receptor antagonists, IV ketamine and magnesium, and less commonly IV memantine, are used to treat acute pain. These drugs are potent antihyperalgesic agents that modulate central sensory processing of pain and potentiate opioid-induced analgesia.36 NMDA receptor antagonists are thought to reduce central sensitization implicated in the development of postsurgical pain syndromes. When McNicol and colleagues reviewed studies in which intraoperative and postoperative subanesthetic IV and epidural ketamine was administered to patients undergoing a variety of different surgeries, including thoracotomy, mastectomy, hysterectomy, and various orthopedic surgeries, they concluded that perioperative IV, but not epidural, ketamine reduced postsurgical pain syndromes at three and six months.37 Subanesthetic IV ketamine also has opioid-sparing effects. In a review of 34 efficacy studies of IV ketamine delivered at dosages of less than 1.2 mg/kg per hour with or without a bolus dose of 1 mg/kg to treat pain from various surgeries, 23 studies reported a 40% mean reduction in opioid consumption.38 While no major adverse events were noted, minor ones included nausea, vomiting, dry mouth, and (rarely) hallucinations.
Alpha-2 agonists, such as clonidine and dexmedetomidine, exert antinociceptive activity by stimulating alpha-2 adrenoreceptors located in the central nervous system.39 When used to manage postoperative pain, these agents have demonstrated 24-hour opioid-sparing effects.40 Clonidine can be administered by IV, epidural, intrathecal, perineural, intraarticular, oral, transdermal, and local infiltration routes; dexmedetomidine is more commonly administered by IV and neuraxial routes. Hypotension is a common adverse effect of perioperative multimodal regimens containing clonidine39 and dexmedetomidine.41 Dexmedetomidine also increases the risk of postoperative bradycardia39 and is typically administered only during surgery and in settings in which patients are closely monitored, such as postanesthesia care or critical care units.
Opioids. There are several subtypes of opioids, of which the most common and potent for effective pain control are the pure opioid agonists, such as morphine, hydromorphone, fentanyl, and oxycodone. Opioid agonists42
- stimulate μ receptors found primarily in the peripheral and central nervous systems.
- inhibit nociception in the spinal cord.
- activate descending pain pathways controlled by circuits from the forebrain and midbrain.
For acute pain, opioids are generally administered by IV and oral routes. Bioavailability of opioid medications varies among the specific subtypes, with the route of administration, and among patients, making it difficult to determine milligram-to-milligram equianalgesic dose ratios.43 Patanwala and colleagues provide suggested equianalgesic dose ratios for IV and oral opioids, but point out that when converting from IV to oral dosing and vice versa, especially with repetitive dosing, clinicians should assess the active metabolite.43
Adverse events associated with μ-opioid agonists include confusion, sedation, hypotension, constipation, dizziness, pruritus, headache, nausea, vomiting, and respiratory depression.44 In addition, the continued use of opioids, even for acute pain, can lead to physical dependence and addiction. For information on opioid prescribing, administration, and monitoring practices to reduce and address opioid abuse and addiction, nurses should consult the 2015 Washington State Agency Medical Directors’ Group guidelines, available online at www.agencymeddirectors.wa.gov. Interactions between opioids and other medications can interfere with opioid metabolism, particularly when other medications are also metabolized via the cytochrome P-450 enzyme system. Nurses should be familiar with factors—such as multidrug regimens, advanced age, and impaired hepatic function—that can affect the cytochrome P-450 pathways, increasing the risk of opioid adverse effects and drug−drug interactions.5, 45 A rare occurrence with perioperative opioids is opioid-induced hyperalgesia (OIH), a nociceptive sensitization associated with opioid use.46 It is often very difficult to diagnose OIH, which is frequently confused with acute opioid tolerance, a progressive decrease in the analgesic response to opioids. OIH can happen with any opioid, but it has been primarily associated with intraoperative remifentanil, though data on other intraoperative opioids are limited.47 When OIH is suspected, opioid doses should be reduced or temporarily discontinued (unless the patient is opioid dependent) while clinicians determine whether pain lessens with the administration of other multimodal analgesic agents.
PCA, which allows self-administration of a prescribed opioid dosage on demand through a delivery device, is a common method of delivering opioids to treat acute postoperative pain, trauma-related pain, severe cancer-related pain, chemotherapy- or radiotherapy-induced mucositis, and pain from sickle cell crisis. PCA is recommended for patients who “require analgesia for more than a few hours and have adequate cognitive function to understand the device and its safety limitations.”1
Morphine and hydromorphone are most frequently prescribed for IV PCA; fentanyl is also used, but less often. In one multicenter study comparing the three opioids, the incidences of opioid-induced respiratory depression, headache, confusion, agitation, and hallucination were not significantly different among the three, though IV fentanyl had a significantly lower rate of such common opioid-induced adverse reactions as nausea, vomiting, pruritus, urinary retention, and sedation.48 Neto and colleagues suggest that methadone, which is rarely used with IV PCA for acute pain, may have advantages in alleviating postsurgical pain from total hip arthroplasty because it acts on pain pathways through NMDA receptor blockade, μ-opioid receptor activation, and norepinephrine and serotonin reuptake inhibition in the central nervous system,49 possibly reducing the likelihood of central sensitization. In that study, methadone significantly reduced overall opioid consumption compared with morphine.49 Because of methadone's highly variable elimination half-life, ranging from eight to 90 hours,49 and its short analgesic duration (four to eight hours), which can lead to drug accumulation during titration, methadone should be prescribed only by clinicians experienced in its use.49
In setting up PCA devices and changing drug cartridges, nurses must verify that the correct drug is being administered to the correct patient at the correct dosage; a double check by two RNs is often hospital policy. A loading dose, which is generally higher than the demand dose, is typically given prior to the start of IV PCA. Evidence summarized in acute pain management guidelines issued by the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (available online at http://fpm.anzca.edu.au/documents/apmse4_2015_final) cautions against the use of a continuous background or basal infusion with opioid-naive patients, as this can increase the likelihood of opioid-induced respiratory depression. Moreover, no convincing data demonstrate increased efficacy with basal infusions for opioid-naive patients, though there may be a stronger rationale for use of basal infusions in opioid-tolerant patients.1 As reported in the recent American Pain Society Principles of Analgesic Use, basal rates for postoperative pain may not improve the quality of analgesia and may increase the incidence and severity of opioid-induced adverse effects, including respiratory depression.50 A meta-analysis of randomized controlled trials comparing the same postoperative opioid (usually morphine) by PCA versus non-PCA, primarily by IV bolus but also by intramuscular, subcutaneous, and oral routes, demonstrated that PCA was more effective than non-PCA for pain control and was associated with greater patient satisfaction; however, PCA was also associated with greater overall opioid consumption and a higher incidence of pruritus.51
Novel PCA technologies. Newer PCA drug delivery technologies have been developed and tested. A transdermal fentanyl patient-controlled iontophoretic delivery system is now approved by the U.S. Food and Drug Administration and indicated for hospital treatment of acute postoperative pain (see Figure 2). It delivers fentanyl 40 mcg transdermally when activated by the patient and is restricted by a 10-minute lockout interval, allowing up to six doses per hour for up to 24 hours, or 80 doses, whichever comes first, at which point a new device must be applied for continued therapy. Maximum duration of therapy is three days (72 hours). Information on the safety and efficacy of the fentanyl iontophoretic transdermal system for postoperative pain is reported in a review by Scott and a meta-analysis by Poon and colleagues.52, 53 Another novel drug delivery system that is approved for use in 33 European countries but not yet in the United States is a sufentanil sublingual tablet system (see Figure 3). This system is a handheld, preprogrammed, noninvasive, patient-activated device that delivers sufentanil 15-mcg microtablets on demand. Safety and efficacy information compiled from numerous studies and randomized, placebo-controlled trials comparing the system to morphine delivery by IV PCA are summarized by Frampton.54 As these novel technologies that require no IV line become available in hospital settings, nurses will require training in their use and education on patient instructions and monitoring.
NEURAXIAL AND PERIPHERAL REGIONAL ANESTHESIA
Multimodal analgesia also includes the use of neuraxial anesthesia, which involves local administration of an anesthetic or opioid into the spinal cord's neuraxial (epidural or intrathecal) space.4 A local anesthetic and opioid combination work synergistically to relieve pain, but no single combination has proven superior to another.3 Strong, high-quality evidence supports the use of epidural analgesia for major thoracic and abdominal procedures specifically in patients at risk for cardiac complications, pulmonary complications, or prolonged ileus.1 Decisions to use epidural analgesia either by single injection or by continuous infusion are often based on research on specific types and locations of pain, ability to closely monitor patients, and availability of anesthesia providers or pain service experts to oversee therapy. Rawal argues that less invasive, regional analgesic techniques may be as good as or better than neuraxial techniques in achieving optimal pain control.55 Duch and Møller, however, found little quality evidence demonstrating the benefit or harm of continuous epidural analgesia for traumatic rib fractures.56 Risks associated with epidural analgesia include hypoventilation, atelectasis, and pneumonia owing to the effects of local anesthetics on respiratory muscles and diaphragmatic excursion. Consequently, epidural analgesia is not used to manage MG's rib fracture pain; instead systemic analgesics are administered.
Regional analgesia also includes peripheral nerve blocks (PNBs) with or without a continuous peripheral nerve block (CPNB) infusion directed toward an isolated nerve or plexus through the injection of a local anesthetic near the neural targets. These techniques allow a localized delivery of analgesia to specific painful areas and augment multimodal regimens. The military has published an extensive manual that illustrates multiple anatomical locations for PNBs and describes ultrasound-guided procedures to accomplish these blocks.57 The manual is available online at www.dvcipm.org/clinical-resources/dvcipm-maraa-book-project. In 2005, the authors of that manual, Buckenmaier and Bleckner, published a comprehensive review of anesthetic agents used with PNBs and CPNBs.58 The delivery of both neuraxial and PNB therapies requires the expertise and oversight of anesthesia providers and pain service experts.
EVIDENCE-BASED PRACTICE GUIDELINES AND EXPERT CONSENSUS
Several evidence-based practice guidelines from professional associations and organizations endorse the use of multimodal analgesia for acute pain. Four of the most recent guidelines were developed by the American Society of Anesthesiologists; the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine; the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia; and the Washington State Agency Medical Directors’ Group (see Table 1).1, 14, 59, 60 To reduce adverse effects from opioids and expand biological targets for pain management, these guidelines recommend the use of both pharmacologic and nonpharmacologic opioid-sparing interventions.
Wound infiltration with local anesthetics is one strategy often recommended as a component of multimodal analgesia.14, 59 This practice can be accomplished by directly injecting an anesthetic into wound sites or joints, or by wound catheter infusions. Rawal summarized the benefits of such techniques in specific surgeries.61
Nonpharmacologic interventions for acute pain should be incorporated into multimodal pain management regimens for acute pain. These interventions, which include cold compresses, massage, physical activity coaching, graded exercise therapy, and behavioral health interventions, act synergistically to relieve pain. A recent study that included 56 nurses demonstrated that music, patient education, and deep breathing relaxation were judged favorably by nurses as evidence-based practice interventions, with nurse comfort levels being moderate to high using these interventions.62 Nurses in this study were less comfortable with acupressure, guided imagery, and massage, viewing these techniques as having limited applicability in practice. Nurses need to understand the benefits of nonpharmacologic measures for acute pain, their mechanisms of action, and how to implement these practices effectively and in accordance with patient preferences, their own willingness to try these measures, and their skill in delivering these interventions (see Table 2).63-84All of these techniques can be used in hospital, ambulatory, and home settings.
MG leaves the operating room with his left arm in a cast and an external fixation device stabilizing his tibial fracture. Because of his uncontrolled hypertension, obstructive sleep apnea, and fractured ribs, he is transferred to the surgical critical care unit and placed on a cardiac and end-tidal carbon dioxide (ETCO2) monitor. A nurse initiates the preventive postoperative pain control plan the care team discussed during surgery. Pain is assessed every one to two hours at all injured sites (left upper arm, left ribs, and lower left leg). Respiratory status (rate, depth, and regularity of respirations) and level of sedation are monitored and documented every hour. Every two hours, when nurses perform neurovascular checks of MG's left lower extremity and left hand (assessing the surgical and femoral catheter sites for bleeding, skin color and temperature, swelling or edema, capillary refill of toenail beds, and motor and sensory function), they ensure that his femoral catheter is patent and that his left lower leg is supported by a pillow. MG is encouraged to use his IV PCA 15 minutes before coughing, turning, deep breathing, and using the incentive spirometer, which he is to do every two hours. His nurse encourages him to use music and TV as sources of distraction, and teaches him to use visual imagery—recalling pleasant moments on his recent vacation—during respiratory care. Other than the mild sedation from general anesthesia and gabapentin, MG remains stable, rating his pain intensity between 2 and 4 at rest and as high as 7 when taking a deep breath. His ETCO2 is occasionally elevated (50 to 55 mmHg), but returns to normal (35 to 45 mmHg) after respiratory care. His wife brings his CPAP device from home for use overnight.
The next morning, MG is transferred to the orthopedic unit. Since he used a total of 8.6 mg of IV hydromorphone by PCA within the first 24 hours after surgery and was expected to experience either constant or episodic pain from his fractures and surgical site over the next week, he is transitioned to a usual starting dose of controlled-release oxycodone, 20 mg every 12 hours, and to oral acetaminophen 650 mg every six hours, along with oxycodone 5 to 10 mg every four to six hours as needed. His femoral catheter is removed at 10 AM by the acute pain service.
The physical therapist helps MG get out of bed using special crutches for his casted left arm and bearing no weight on his left leg. He goes to the physical therapy unit two times for one-hour instruction sessions on crutch walking and safely using stairs. Nurses continue to monitor his vital signs and sedation level, performing neurovascular checks every four hours. He uses his incentive spirometer every four hours, and remains on continuous ETCO2 monitoring. His recovery progresses, and his pain is well controlled.
The following day, MG is discharged to home with an analgesic regimen of controlled-release oxycodone 10 mg every 12 hours, gabapentin 200 mg every eight hours around the clock, oxycodone 5 mg every four to six hours, and acetaminophen 650 mg every six hours as needed. A bowel regimen with senna 15 mg twice a day is continued to prevent opioid-induced constipation. Arrangements are made for a home health nurse to visit him daily for five consecutive days to assess pain, check his respiratory and neurovascular status, and inspect his external fixation site for wound healing and signs of infection. A follow-up appointment in one week is arranged with the trauma service.
MG has a successful outcome with his aggressive multimodal plan of care. One week following discharge, he no longer needs controlled-release oxycodone and is taking only short-acting oxycodone 5 mg two to three times daily. He is tapering off gabapentin, reducing the dosage by 100 mg per day. Two weeks after discharge, he is only taking acetaminophen 650 mg as needed and walking with crutches without any difficulty.
ENHANCED POSTOPERATIVE RECOVERY AND FUNCTION
Research demonstrates that multimodal analgesia not only reduces pain, opioid use, and opioid-related adverse effects, but also enhances postoperative recovery and function, and increases patient satisfaction. When regional analgesia was added to a systemic regimen of acetaminophen, gabapentin, and systemic opioids for operative repair of tibial and ankle fractures (similar to MG's regimen and surgery), patients receiving regional analgesia reported significantly higher satisfaction with pain management (P = 0.005) and a higher mean quality of recovery score at 24 hours (P = 0.04) compared with those who received no regional analgesia.85 Similarly, Lee and colleagues found that, for patients undergoing upper extremity surgery, a multimodal analgesic regimen—which included preoperative and postoperative ibuprofen 800 mg, celecoxib 400 mg, and pregabalin 75 mg daily—added to the standard postoperative regimen of oral oxycodone 10 mg every 12 hours and acetaminophen 650 mg three times daily, significantly improved satisfaction at discharge (P = 0.001) compared with IV PCA postoperatively up to day 3 and the standard postoperative oxycodone and acetaminophen regimen.86
IMPLICATIONS FOR NURSES
To make the case for multimodal analgesia for acute pain, nurses in all health care settings must be knowledgeable about classes of analgesics, mechanisms of action in the peripheral and central nervous systems, routes of administration, recommended dosing, adverse effect profiles, drug-to-drug synergistic effects and interactions, and contraindications. Likewise, nurses should be familiar with research and evidence-based practice guidelines for specific types of pain. While multimodal analgesia should be considered for all patients with acute pain, attention should be given to patients at elevated risk for developing chronic postsurgical pain syndrome and other opioid-related adverse effects. In tailoring multimodal regimens to individual patients, interprofessional collaboration with pain experts (anesthesiologists, pain management nurses, and pharmacists) is important. In addition, nurses should be provided competency-based education that emphasizes multimodal analgesic approaches for acute pain management and clinical decision making in designing analgesic regimens and developing nursing plans of care. Competencies in delivering multimodal therapies and monitoring patients should be evaluated.
Patient education is an integral part of multimodal pain management. Patients need to understand the rationale for their treatment and for the use of all medications and interventions both during and after hospitalization. It is critical that patients receiving multimodal analgesia be provided both oral and written instructions about the medications they are using. This should include
- the names of all pain medications.
- how each medication works.
- dosages and dosing schedules.
- common and serious adverse effects.
Patients should also be told to notify their health care providers if they are not deriving acceptable pain relief or if they experience any adverse effects, including constipation. If taking opioids or agents that produce sedation, patients should be advised to avoid alcohol, operating machinery, and driving.
1. Chou R, et al Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council J Pain 2016 17 2 131–57
2. Kehlet H, Dahl JB The value of “multimodal” or “balanced analgesia” in postoperative pain treatment Anesth Analg 1993 77 5 1048–56
3. Gritsenko K, et al Multimodal therapy in perioperative analgesia Best Pract Res Clin Anaesthesiol 2014 28 1 59–79
4. Argoff CE Recent management advances in acute postoperative pain Pain Pract 2014 14 5 477–87
5. Gudin J Opioid therapies and cytochrome p450 interactions J Pain Symptom Manage 2012 44 6 Suppl S4–S14
6. Jarzyna D, et al American Society for Pain Management Nursing guidelines on monitoring for opioid-induced sedation and respiratory depression. Pain Manag Nurs
7. Kelly DJ, et al Preemptive analgesia I: physiological pathways and pharmacological modalities Can J Anaesth 2001 48 10 1000–10
8. Weinbroum AA Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids Pharmacol Res 2012 65 4 411–29
9. Vadivelu N, et al Review of perioperative pain management of opioid-dependent patients J Opioid Manag 2016 12 4 289–301
10. Dahl JB, Kehlet H Preventive analgesia Curr Opin Anaesthesiol 2011 24 3 331–8
11. Joshi GP, et al Procedure-specific pain management and outcome strategies Best Pract Res Clin Anaesthesiol 2014 28 2 191–201
12. Pozek JP, et al The acute to chronic pain transition: can chronic pain be prevented? Med Clin North Am 2016 100 1 17–30
13. Simpson D, et al Ropivacaine: a review of its use in regional anaesthesia and acute pain management Drugs 2005 65 18 2675–717
14. American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology
15. Bozimowski G A review of nonsteroidal anti-inflammatory drugs AANA J 2015 83 6 425–33
17. Nir RR, et al Preoperative preemptive drug administration for acute postoperative pain: a systematic review and meta-analysis Eur J Pain 2016 20 7 1025–43
18. Maund E, et al Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review Br J Anaesth 2011 106 3 292–7
19. Chen JY, et al Opioid-sparing effects of ketorolac and its correlation with the recovery of postoperative bowel function in colorectal surgery patients: a prospective randomized double-blinded study Clin J Pain 2009 25 6 485–9
20. Murphy EJ Acute pain management pharmacology for the patient with concurrent renal or hepatic disease Anaesth Intensive Care 2005 33 3 311–22
21. Giannoudis PV, et al Inflammation, bone healing, and anti-inflammatory drugs: an update J Orthop Trauma 2015 29 Suppl 12 S6–S9
22. Pountos I, et al Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis ScientificWorldJournal 2012 2012 606404
23. Donohue D, et al Ketorolac administered in the recovery room for acute pain management does not affect healing rates of femoral and tibial fractures J Orthop Trauma 2016 30 9 479–82
24. Paulasir S, et al Nonsteroidal anti-inflammatory drugs: do they increase the risk of anastomotic leaks following colorectal operations? Dis Colon Rectum 2015 58 9 870–7
25. Smith HS Potential analgesic mechanisms of acetaminophen Pain Physician 2009 12 1 269–80
26. McNicol ED, et al Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain Cochrane Database Syst Rev 2016 5 CD007126
27. Sinatra RS, et al Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery Anesthesiology 2005 102 4 822–31
28. Jibril F, et al Intravenous versus oral acetaminophen for pain: systematic review of current evidence to support clinical decision-making Can J Hosp Pharm 2015 68 3 238–47
29. Smith HS Perioperative intravenous acetaminophen and NSAIDs Pain Med 2011 12 6 961–81
30. Schmidt PC, et al Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain Anesthesiology 2013 119 5 1215–21
31. Tiippana EM, et al Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety Anesth Analg 2007 104 6 1545–56
32. Arumugam S, et al Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis J Pain Res 2016 9 631–40
33. Mathiesen O, et al Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure BMC Anesthesiol 2007 7 6
34. Turan A, et al Effect of oral gabapentin on postoperative epidural analgesia Br J Anaesth 2006 96 2 242–6
35. Clarke H, et al Pregabalin reduces postoperative opioid consumption and pain for 1 week after hospital discharge, but does not affect function at 6 weeks or 3 months after total hip arthroplasty Br J Anaesth 2015 115 6 903–11
36. Suzuki M Role of N-methyl-D-aspartate receptor antagonists in postoperative pain management Curr Opin Anaesthesiol 2009 22 5 618–22
37. McNicol ED, et al A systematic review and meta-analysis of ketamine for the prevention of persistent post-surgical pain Acta Anaesthesiol Scand 2014 58 10 1199–213
38. Jouguelet-Lacoste J, et al The use of intravenous infusion or single dose of low-dose ketamine for postoperative analgesia: a review of the current literature Pain Med 2015 16 2 383–403
39. Blaudszun G, et al Effect of perioperative systemic alpha2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials Anesthesiology 2012 116 6 1312–22
40. Chan AK, et al Alpha-2 agonists in acute pain management Expert Opin Pharmacother 2010 11 17 2849–68
41. Jessen Lundorf L, et al Perioperative dexmedetomidine for acute pain after abdominal surgery in adults Cochrane Database Syst Rev 2016 2 CD010358
42. Krenzischek DA, et al Pharmacotherapy for acute pain: implications for practice J Perianesth Nurs 2008 23 1 Suppl S28–S42
43. Patanwala AE, et al Opioid conversions in acute care Ann Pharmacother 2007 41 2 255–66
44. Vallerand AH, et al Davis's drug guide for nurses
. 15th ed. Philadelphia: F.A. Davis Company; 2017.
45. Smith HS The metabolism of opioid agents and the clinical impact of their active metabolites Clin J Pain 2011 27 9 824–38
46. Yu EH, et al Remifentanil tolerance and hyperalgesia: short-term gain, long-term pain? Anaesthesia 2016 71 11 1347–62
47. Fletcher D, Martinez V Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis Br J Anaesth 2014 112 6 991–1004
48. Hutchison RW, et al A comparison of a fentanyl, morphine, and hydromorphone patient-controlled intravenous delivery for acute postoperative analgesia: a multicenter study of opioid-induced adverse reactions Hosp Pharm 2006 41 7 659–63
49. Neto JO, et al Methadone patient-controlled analgesia for postoperative pain: a randomized, controlled, double-blind study J Anesth 2014 28 4 505–10
50. Herndon CM, et al Principles of analgesic use 2016 7th ed. Chicago American Pain Society
51. McNicol ED, et al Patient controlled opioid analgesia versus non-patient controlled opioid analgesia for postoperative pain Cochrane Database Syst Rev 2015 6 CD003348
52. Poon KH, et al Efficacy of fentanyl iontophoretic transdermal system in postoperative pain—a meta-analysis Acute Pain 2009 11 2 65–74
53. Scott LJ Fentanyl iontophoretic transdermal system: a review in acute postoperative pain Clin Drug Investig 2016 36 4 321–30
54. Frampton JE Sublingual sufentanil: a review in acute postoperative pain Drugs 2016 76 6 719–29
55. Rawal N Epidural technique for postoperative pain: gold standard no more? Reg Anesth Pain Med 2012 37 3 310–7
56. Duch P, Møller MH Epidural analgesia in patients with traumatic rib fractures: a systematic review of randomised controlled trials Acta Anaesthesiol Scand 2015 59 6 698–709
58. Buckenmaier CC III, Bleckner LL Anaesthetic agents for advanced regional anaesthesia Drugs 2005 65 6 745–59
61. Rawal N Current issues in postoperative pain management Eur J Anaesthesiol 2016 33 3 160–71
62. Sidani S, et al Nurses’ perceptions of interventions for the management of patient-oriented outcomes: a key factor for evidence-based practice Worldviews Evid Based Nurs 2016 13 1 66–74
63. Tiidus PM Alternative treatments for muscle injury: massage, cryotherapy, and hyperbaric oxygen Curr Rev Musculoskelet Med 2015 8 2 162–7
64. Nadler SF, et al The physiologic basis and clinical applications of cryotherapy and thermotherapy for the pain practitioner Pain Physician 2004 7 3 395–9
65. Kol E, et al Evaluation of the outcomes of ice application for the control of pain associated with chest tube irritation Pain Manag Nurs 2013 14 1 29–35
66. Watkins AA, et al Ice packs reduce postoperative midline incision pain and narcotic use: a randomized controlled trial J Am Coll Surg 2014 219 3 511–7
67. Furlan AD, et al Massage for low-back pain Cochrane Database Syst Rev 2015 9 CD001929
68. Ucuzal M, Kanan N Foot massage: effectiveness on postoperative pain in breast surgery patients Pain Manag Nurs 2014 15 2 458–65
69. Adams MHA, et al The effects of massage therapy on pain management in the acute care setting Int J Ther Massage Bodywork 2010 3 1 4–11
70. Bauer BA, et al Effect of massage therapy on pain, anxiety, and tension after cardiac surgery: a randomized study Complement Ther Clin Pract 2010 16 2 70–5
71. Field T Massage therapy research review Complement Ther Clin Pract 2014 20 4 224–9
72. Waters-Banker C, et al Investigating the mechanisms of massage efficacy: the role of mechanical immunomodulation J Athl Train 2014 49 2 266–73
73. Lewandowski W, Jacobson A Bridging the gap between mind and body: a biobehavioral model of the effects of guided imagery on pain, pain disability, and depression Pain Manag Nurs 2013 14 4 368–78
74. Sears SR, et al Evaluation of “Steps to Surgical Success” (STEPS): a holistic perioperative medicine program to manage pain and anxiety related to surgery Holist Nurs Pract 2013 27 6 349–57
75. Nelson EA, et al Systematic review of the efficacy of pre-surgical mind-body based therapies on post-operative outcome measures Complement Ther Med 2013 21 6 697–711
76. Gonzales EA, et al Effects of guided imagery on postoperative outcomes in patients undergoing same-day surgical procedures: a randomized, single-blind study AANA J 2010 78 3 181–8
77. Gard T, et al Pain attenuation through mindfulness is associated with decreased cognitive control and increased sensory processing in the brain Cereb Cortex 2012 22 11 2692–702
78. Loreto-Quijada D, et al Differential effects of two virtual reality interventions: distraction versus pain control Cyberpsychol Behav Soc Netw 2014 17 6 353–8
79. Kohl A, et al Acceptance, cognitive restructuring, and distraction as coping strategies for acute pain J Pain 2013 14 3 305–15
80. Burns JW, et al Specific and general therapeutic mechanisms in cognitive behavioral treatment of chronic pain J Consult Clin Psychol 2015 83 1 1–11
81. Koranyi S, et al Psychological interventions for acute pain after open heart surgery Cochrane Database Syst Rev 2014 5 CD009984
82. Vance CG, et al Using TENS for pain control: the state of the evidence Pain Manag 2014 4 3 197–209
83. Johnson MI, et al Transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults Cochrane Database Syst Rev 2015 8 CD007264
84. Johnson MI, et al Transcutaneous electrical nerve stimulation for acute pain Cochrane Database Syst Rev 2015 6 CD006142
85. Elkassabany N, et al Does regional anesthesia improve the quality of postoperative pain management and the quality of recovery in patients undergoing operative repair of tibia and ankle fractures? J Orthop Trauma 2015 29 9 404–9
86. Lee SK, et al Is multimodal analgesia as effective as postoperative patient-controlled analgesia following upper extremity surgery? Orthop Traumatol Surg Res 2013 99 8 895–901
Keywords:Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
acute pain; multimodal analgesia; nondrug measures for acute pain; opioids; postoperative pain