Trauma-related injuries are common and burdensome. In 2011, injuries were responsible for more than 40 million visits to emergency departments (EDs) in the United States (National Center for Health Statistics & Ambulatory and Hospital Care Statistics Branch, n.d.). Pain is reported in at least 70% of trauma-related injuries (Berben, Schoonhoven, Meijs, van Vugt, & van Grunsven, 2011), and undertreated acute pain may contribute to delirium, particularly in geriatric patients (McKeown, 2015); prolonged need for mechanical ventilation; and delayed mobilization (Barr et al., 2013). Acute pain is cited as a predictor of chronic pain development (McGreevy, Bottros, & Raja, 2011; Trevino, Harl, Deroon-Cassini, Brasel, & Litwack, 2014). Even at 4 months after injury, 79% of trauma patients reported chronic pain, with positive correlations between pain severity and the level of interference with activities of daily life (Trevino, Essig, deRoon-Cassini, & Brasel, 2012). A study among veterans revealed that 73.4% experience persistent pain, possibly because of combat and blast injuries (Higgins et al., 2014). Effective acute pain management is expected to improve the patient experience and potentially prevent long-term effects.
Opioids have historically been the mainstay treatment for severe trauma pain (Aldington, McQuay, & Moore, 2011; Gausche-Hill et al., 2014; Keene, Rea, & Aldington, 2011). As an example of the reliance on opioid analgesics, a 2010 study indicated that 31% of all ED visits involved the administration of an opioid (Mazer-Amirshahi, Mullins, Rasooly, van den Anker, & Pines, 2014). However, opioids can cause adverse events (AEs) that limit their use in trauma pain management. These AEs are well known and include nausea, vomiting, and constipation (Keene et al., 2011). Of greatest concern is the risk of opioid-induced sedation and its progression to respiratory depression, which may lead to injury or death (Jarzyna et al., 2011). The concomitant use of sedating medications, especially benzodiazepines, increases the risk of sedation and of diminishing respiratory drive (Jarzyna et al., 2011).
Additional concerns with the use of opioids are related to the risks of misuse by patients and of substance abuse. Misuse is defined as the “use of a medication (for a medical purpose) other than as directed or indicated, whether willful or unintentional, and whether harm results or not,” and substance abuse is defined as “any use of an illegal drug, or the intentional self-administration of a medication for a nonmedical purpose such as altering one's state of consciousness, for example, getting high” (Chou et al., 2009, p. 130; Katz et al., 2007, p. 650). Abuse may contribute to injuries, as suggested by a survey in which 38% of trauma populations displayed problematic/risky alcohol behavior and 44% of those with toxicology results tested positive for illicit drugs (Stroud, Bombardier, Dyer, Rimmele, & Esselman, 2011). An observational study showed that 42% of patients discharged with opioids from a level 1 trauma center ED misused these drugs (Beaudoin, Straube, Lopez, Mello, & Baird, 2014). Individuals who are opioid dependent as a result of substance abuse report lower quality of life than the general population (Griffin et al., 2015).
Opioids are often required for moderate to severe trauma pain, but they are increasingly used at lower doses as part of opioid-sparing and multimodal analgesic approaches (Figure 1). This shift is due to both the demonstrated effectiveness of multimodal pain management (American Society of Anesthesiologists Task Force on Acute Pain Management, 2012; Cho et al., 2011) and the widely recognized dangers associated with opioid use, misuse, and abuse (Beaudoin et al., 2014; Keene et al., 2011). Opioid-sparing strategies can mitigate the undesirable effects of opioids by facilitating the use of the lowest effective dose of opioids (Jarzyna et al., 2011). Multimodal regimens involve the use of multiple medications (e.g., opioids and nonopioids) with different mechanisms of action (Figure 2) as well as nonpharmacologic interventions to achieve more effective analgesia. Use of multiple analgesics allows for lower and safer doses of each drug (Jarzyna et al., 2011). This review aims to summarize evidence on pharmacologic and nonpharmacologic options that may be utilized in opioid-sparing, multimodal therapy for trauma pain. The main focus is the treatment of pain during hospitalization, with consideration for discharge planning.
PATIENT ASSESSMENT AND COMMUNICATION
Pain assessment (e.g., intensity level, nature and quality, duration, location) is key to developing a pain management plan of care for trauma patients. Pain intensity scales can help patients communicate their pain. Appropriate scales should be selected on the basis of a patient's age and cognitive status. Patient self-report is the gold standard for determining pain intensity (Gélinas, 2016). Adults who are able to self-report their pain intensity should use a validated visual analog scale or a validated numeric rating scale (Gausche-Hill et al., 2014; Hjermstad et al., 2011). For patients aged 4–12 years, a validated self-report tool such as the Wong-Baker FACES® scale is suggested (Garra et al., 2010; Gausche-Hill et al., 2014).
Patients who are unable to communicate verbally are at particular risk for undertreatment of pain (Barr et al., 2013; Gausche-Hill et al., 2014; Pasero & McCaffery, 2011; Reavey et al., 2014). For these patients, a hierarchy of pain assessment techniques (Figure 3) has been recommended that involves assuming pain is present for conditions that are typically painful and includes both formal tools and practitioner observations (Pasero & McCaffery, 2011). In critically ill patients who cannot self-report, scales such as the Critical-Care Pain Observation Tool, which can be used for intubated and extubated patients, or the Behavioral Pain Scale should be utilized. For patients younger than 4 years, available scales include the Face, Legs, Arms, Cry, and Consolability scale and the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). For patients younger than 3 months, the Neonatal Pain, Agitation, and Sedation Scale (N-PASS) is recommended. When using behavioral tools, practitioners should remember that the absence of pain-related behaviors does not always indicate the absence of pain.
Evaluating pain intensity with a valid and appropriate scale is only one component of a comprehensive pain assessment. In addition, assessments of the character of pain (e.g., sharp, dull, aching, cramping, burning), pattern (e.g., radiating, intermittent, constant), duration, location, and interventions that make pain better or worse are key to identifying the most appropriate and effective treatments for the type of pain, such as somatic, visceral, and neuropathic (Vadivelu, Urman, Hines, & Kunnumpurath, 2011). In the trauma patient, somatic pain is typically the result of a fracture or a muscular injury that is well localized and described as aching, sharp, or stabbing. Deep injuries of the liver, pancreas, or bowel are examples of trauma that causes visceral pain, which is more diffuse than somatic pain and is typically described as a pressure, cramping, aching, or sharp pain. Neuropathic pain, often the most difficult to treat, can result from injury to nerves; this type of pain is classically described as burning, tingling, electric, or lancinating.
Communication between health care providers and patients is important to establish positive relationships and rapport and may reduce patient anxiety, support patients' sense of security, increase patient satisfaction, and enhance treatment efficacy. Discussing realistic expectations for pain management enables patients to participate in treatment decisions and improves the likelihood of satisfaction with the plan of care (Georgy, Carr, & Breen, 2011). Focusing on the patient's ability to meet functional goals instead of reaching an arbitrary pain rating score reinforces the concept of having realistic expectations. Nonjudgmental communications (especially if alcohol or drug abuse was implicated in the injury) and advocating for multimodal analgesia that targets the source of the pain can improve nurse-patient relationships and patient care.
To mitigate risks of opioid abuse and dependency, assessing patients for risk of opioid abuse with a screening tool, reducing the dose as the pain abates, and educating patients that opioids will be administered for a limited period are suggested (Macintyre, Huxtable, Flint, & Dobbin, 2014). Appropriate weaning from opioids (Chou et al., 2016; Washington State Agency Medical Directors' Group, 2015) could prevent withdrawal symptoms and therefore misuse, because patients may administer opioids to prevent the experience of withdrawal when pain is no longer present. Discussions of patient expectations and assessing the risk of opioid abuse have the potential to improve patient satisfaction and safe care (Browne, Andrews, Schug, & Wood, 2011; Georgy et al., 2011; Macintyre et al., 2014).
A PubMed literature search was performed on September 3, 2015. To obtain studies in trauma populations, the following search terms were included: trauma, injury, fracture, combat trauma, and amputation. To focus on end points of interest, the search terms analgesic effect, pain management, safety, and opioid-sparing were also used. Studies on specific interventions requested by the authors were obtained through inclusion of the following search terms: intravenous acetaminophen, oral acetaminophen, oral NSAID, topical NSAID, topical local anesthetic, gabapentin, pregabalin, amitriptyline, ketamine, regional techniques, nonpharmacological, distraction techniques, relaxation techniques, touch therapy, cognitive behavioral therapy, acupuncture, massage, biofeedback, cryotherapy, and TENS. To focus on high-quality data and evidence-based recommendations, the search terms clinical trial, prospective study, review of utilization, and guideline were included.
The following terms were excluded to omit articles outside the scope of this review: survival, death, chronic, cancer, stroke, case, and feasibility study. Articles from the initial literature search were required to be published in the last 5 years (September 5, 2010, to September 3, 2015), be in English, and have human subjects. In total, 166 citations were obtained through the literature search; 58 additional citations were included at the discretion of the authors (Table, Supplemental Digital Content 1 [available at: https://links.lww.com/JTN/A0], which shows additional citations). The additional citations were not required to adhere to the restrictions of the original literature search (e.g., articles could be published >5 years ago) to address gaps and allow for inclusion of older landmark studies. After the citations were filtered for appropriateness of topic, 91 remained (Figure 4). To indicate the scientific rigor and possible biases in each study, the brief summaries in the Results section specify whether blinding was part of the study design. Uncited recommendations and observations are expert opinions of the authors.
The following sections summarize data on pharmacologic and nonpharmacologic options for opioid-sparing and multimodal treatment of trauma pain. Extensive discussion of systemic opioids is beyond the scope of this article because it focuses on strategies to move beyond overreliance on these agents, which have been the mainstay of treatment. In addition, a detailed analysis of opioids in the trauma environment was deemed redundant with previous reviews (Dijkstra, Berben, van Dongen, & Schoonhoven, 2014; Gausche-Hill et al., 2014). The summarized studies primarily focus on the acute treatment of trauma pain, though data from the postsurgical environment are sometimes included because opioid-sparing and multimodal therapy have demonstrated efficacy in this clinical setting (Laskowski, Stirling, McKay, & Lim, 2011; Melemeni, Staikou, & Fassoulaki, 2007) and trauma patients may require surgery. It should be noted that the search terms amitriptyline, massage, biofeedback, transcutaneous electrical nerve stimulation (TENS), and touch therapy did not return any relevant recent studies. As such, these techniques are not reviewed. A summary of key advantages and disadvantages of each type of therapy discussed is included in Table 1.
TABLE 1 -
Summary of the Key Advantages and Disadvantages Associated With Each Type of Analgesic Discussed in the Review
||Key Clinical Advantages
||Key Clinical Disadvantages
||Long history of safety and efficacy in oral and IV routes; IV route may be opioid sparing and have faster onset of action and less hepatotoxicity than oral route
||Can be hepatotoxic at high doses or in at-risk populations
||Effective across multiple routes (e.g., oral, IM, IV)
||Nonsystemic administration is associated with local AEs
|Topical local anesthetics
||May be locally effective for neuropathic pain associated with trauma
||Several studies did not show significant pain relief for various types of trauma pain
||Some evidence for efficacy for neuropathic pain associated with trauma; opioid sparing
||Not all studies support efficacy for trauma pain
||Can reduce painful muscle spasms
||Caution is warranted because of AEs such as dizziness and drowsiness
|Alpha-2 adrenergic agonists
||Sedative and anxiolytic properties; opioid sparing
||Should be used with caution in hemodynamically unstable patients
||May decrease incidence of pain hypersensitivity and opioid tolerance; opioid sparing
||Requires provider training and patient monitoring
||A variety of effective techniques are available to target pain at various locations; opioid sparing
||Require provider training; caution should be exercised if the patient is receiving anticoagulation therapy
||May be safe and simple to implement; opioid sparing
||Are considered complementary to and not a substitute for analgesics; studies supporting their efficacy are typically not double-blind
Abbreviations: AE, adverse event; IM, intramuscular; IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug.
Standard Oral and Intravenous Medications
Oral acetaminophen has a long history as an analgesic, and its mechanism of action involves the inhibition of prostaglandin synthesis (Oyler et al., 2015). A study of osteoarticular injuries in the ED showed significantly improved pain intensity with oral acetaminophen over time (Viallon et al., 2007). At doses higher than 4,000 mg/day, the limit set by the U.S. Food and Drug Administration, acetaminophen is associated with hepatotoxicity (U.S. Food and Drug Administration, 2011). In patients with compromised liver function, including many elderly patients and those abusing alcohol, the use of any level of acetaminophen requires caution (Oyler et al., 2015). Because an estimated 16.4% of injuries in EDs are attributable to alcohol, the safety risk of acetaminophen products related to alcohol should be considered when creating an analgesic plan (Cherpitel et al., 2015).
The mechanism of action of oral and intravenous (IV) acetaminophen is the same (Oyler et al., 2015). Although IV acetaminophen was approved in the United States in 2010, it has a longer history of efficacy and safety because of its availability in Europe since 2002 (Viscusi, Singla, Gonzalez, Saad, & Stepanian, 2012). Pain relief with IV acetaminophen was similar to that with IV morphine in a double-blind study of traumatic limb pain (Craig, Jeavons, Probert, & Benger, 2012). Comparable pain scores for IV acetaminophen plus oral oxycodone versus IV morphine were also observed in a double-blind trial in patients with acute bone fracture (Zare et al., 2014). In a pharmacokinetics study, IV acetaminophen achieved earlier and higher peak plasma levels than an equivalent dose of oral acetaminophen, which may contribute to faster pain relief (Singla et al., 2012). According to analyses of a pharmacokinetic first-pass model, IV acetaminophen results in one-half of the peak hepatic concentration of the oral formulation (Royal, Gosselin, Pan, Mouksassi, & Breitmeyer, 2010). This suggests that IV acetaminophen may carry a reduced risk of hepatotoxicity compared with oral acetaminophen (Royal et al., 2010). No evidence of hepatotoxicity was observed with IV acetaminophen after administration of 5 g across 24 hr, a higher dosage than recommended (Gregoire et al., 2007).
A guideline on the treatment of patients in medical, surgical, and trauma intensive care units (ICUs) recommends IV acetaminophen, among other analgesics, as an adjunctive pain medication to reduce opioid requirements (Barr et al., 2013). A study of patients with hip fracture showed that less IV morphine was required for breakthrough pain in the group that received scheduled IV acetaminophen with as-needed oral opioids than in the control group that received oral acetaminophen plus scheduled oral opioids (Tsang, Page, & Mackenney, 2013). In summary, data suggest that IV acetaminophen effectively relieves pain, may have a faster onset of action than oral acetaminophen, is theoretically less hepatotoxic than oral acetaminophen, and is opioid-sparing; these properties may be advantageous in trauma populations, including military patients with combat-related injuries (Vokoun, 2015). Overall, acetaminophen is considered an effective analgesic that can be included in a multimodal analgesic plan when contraindications and safety issues are considered (Barr et al., 2013; Oyler et al., 2015).
Nonsteroidal Anti-inflammatory Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their opioid-sparing analgesic effects through inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) (Oyler et al., 2015) and have been recommended as adjunctive analgesics in the ICU (Barr et al., 2013). Oral ibuprofen demonstrated similar efficacy as orally administered morphine in a double-blind trial of children with fractures (Poonai et al., 2014). Oral ibuprofen has also shown analgesic efficacy similar to that of acetaminophen, and no difference in efficacy was observed for the combination of NSAID plus acetaminophen versus either alone in a double-blind trial of adult ED patients with acute musculoskeletal pain (Bondarsky et al., 2013). However, a systematic review suggests that the combination of acetaminophen and an NSAID may improve analgesia versus each drug alone (Ong, Seymour, Lirk, & Merry, 2010). The effect of NSAIDs on bone healing is controversial (Dodwell et al., 2010; Pountos, Georgouli, Calori, & Giannoudis, 2012), but a meta-analysis showed no increased risk of failed bone healing (nonunion) for oral, IV, and intramuscular NSAIDs (Dodwell et al., 2010).
Various routes for NSAIDs may have different advantages, limitations, and effects. Intramuscular formulations may be appropriate for patients who are unable to receive oral medications and do not yet have IV access. Intravenous administration is believed to provide the fastest relief, but additional study is needed (Tramèr et al., 1998). Regarding safety, local AEs such as site dermatologic reactions have been most commonly reported with topical, intramuscular, and rectal administration (Kuehl, Carr, Yanchick, Magelli, & Rovati, 2011; Tramèr et al., 1998). Systemic NSAIDs can cause gastrointestinal bleeding and renal issues, but serious events are rare with short-term use for trauma pain (Jones & Lamdin, 2010). Cyclooxygenase-2 selective inhibitors (e.g., celecoxib, meloxicam) are associated with an even lower risk of gastrointestinal AEs than other NSAIDs (Jones & Lamdin, 2010). In addition, COX-2 selective inhibitors showed minimal effects on platelet function in a physician-blinded study (Graff et al., 2007), which suggests a reduced risk of bleeding with these drugs. Nonsteroidal anti-inflammatory drugs have proven efficacy, are opioid sparing, and are versatile analgesics because of their multiple routes of administration.
Topical Local Anesthetics
Topical local anesthetics (e.g., lidocaine, tetracaine) are hypothesized to block local pain signals (Desai et al., 2014; Gimbel, Linn, Hale, & Nicholson, 2005). Evidence suggests that topical application is at least as effective as injection of local anesthesia in patients with lacerations (Jenkins, Murphy, Little, McDonald, & McCarron, 2014). A lidocaine emulsion formulation and an aqueous solution were equally effective at reducing pain during dressing changes in a double-blind trial of burn patients (Desai et al., 2014). Lidocaine patches and plaster have shown efficacy for low back pain (Gimbel et al., 2005) and neuropathic pain related to disk herniation (Likar, Kager, Obmann, Pipam, & Sittl, 2012). Topical lidocaine did not show efficacy for pain associated with traumatic rib fracture (Ingalls, Horton, Bettendorf, Frye, & Rodriguez, 2010), and topical tetracaine did not significantly reduce pain associated with corneal abrasions (Waldman, Densie, & Herbison, 2014); both studies with negative results were double-blind. The rib fracture study may have been underpowered (Fabricant, Ham, Mullins, & Mayberry, 2013), and a more recent trial showed efficacy of the lidocaine patch in patients with rib fractures (Zink, Mayberry, Peck, & Schreiber, 2011). Thus, topical anesthetics can be effective in trauma pain.
Gabapentinoids are anticonvulsants that modulate sodium and calcium channels (Guy, Mehta, Leff, Teasell, & Loh, 2014) and are used to treat acute and chronic neuropathic pain. These medications are recommended as adjunctive analgesics by ICU guidelines (Barr et al., 2013). According to a systematic review, oral gabapentin and pregabalin successfully relieve chronic neuropathic pain after spinal cord injury (Guy et al., 2014). Furthermore, in a pooled analysis of two double-blind trials, pregabalin was associated with superior pain reduction versus placebo in patients with chronic neuropathic pain related to spinal cord injury (Parsons, Sanin, Yang, Emir, & Juhn, 2013). Gabapentin and pregabalin led to decreased pain versus placebo in two double-blind studies of patients with burns (Gray et al., 2011; Rimaz et al., 2012). In addition to analgesic effects, data in the postoperative setting from reviews and a meta-analysis strongly demonstrate the opioid-sparing effects of gabapentin and pregabalin (Gilron, 2007; Melemeni et al., 2007; Zhang, Ho, & Wang, 2011).
Gabapentinoids have not shown analgesic efficacy in all studies, including two double-blind trials (Pfizer, 2015a; Wibbenmeyer et al., 2014). Although the U.S. Department of Veterans Affairs and the U.S. Department of Defense (2007) recommend gabapentin and pregabalin as options for the treatment of neuropathic pain associated with amputation, gabapentin did not significantly reduce postamputation pain in a double-blind study (Nikolajsen et al., 2006).
Gabapentin and pregabalin vary in their pharmacokinetic properties and therapeutic effects. Pregabalin is absorbed more quickly than gabapentin (Gilron, 2007), and patients may experience improved neuropathic pain relief when switching from gabapentin to pregabalin (Toth, 2010). Transitions between the two drugs should be gradual across 7 or more days because of potential withdrawal symptoms (Pfizer, 2015b,2016). Gabapentin and pregabalin may be appropriate for neuropathic pain associated with trauma, and the choice of gabapentinoid varies on the basis of patient characteristics and goals.
Muscle relaxants are a broad category of drugs, but many (e.g., tizanidine, cyclobenzaprine) act to reduce painful muscle spasms (van Tulder, Touray, Furlan, Solway, & Bouter, 2003). Muscle relaxants effectively relieve nonspecific low back pain, including that from injuries (van Tulder et al., 2003). High-quality evidence suggests that tizanidine plus analgesics is more effective at pain relief than placebo plus analgesics in patients with acute low back pain (van Tulder et al., 2003). However, a double-blind trial did not show benefit for routinely adding cyclobenzaprine to NSAIDs in ED patients with acute cervical strain (Khwaja, Minnerop, & Singer, 2010). Muscle relaxants are effective analgesics, but caution is advised because of the associated AEs of dizziness and drowsiness (van Tulder et al., 2003).
Alpha-2 Adrenergic Agonists
The alpha-2 adrenergic agonist activity of clonidine and dexmedetomidine contributes to their opioid-sparing analgesia as well as their sedative and anxiolytic effects, which may be achieved without respiratory depression (Bernard, Hommeril, Passuti, & Pinaud, 1991; Keating, 2015; Oyler et al., 2015; Panzer, Moitra, & Sladen, 2011). In a double-blind study of spine surgery patients, both low-dose ketamine and dexmedetomidine infusions provided good analgesia and decreased rescue opioid use compared with saline (Garg et al., 2016). However, oral dexmedetomidine is not as strong an analgesic as oral ketamine according to a double-blind study of patients undergoing burn wound dressing changes (Kundra, Velayudhan, Krishnamachari, & Gupta, 2013). Clonidine, which is available for multiple routes of administration including oral, has long been used to treat hypertension and may be an opioid-sparing addition to multimodal analgesia (Oyler et al., 2015). A review highlighted sedative and opioid-sparing analgesic properties of oral clonidine that support its use in critically ill military patients with trauma as well as in civilian patients with trauma (Malchow & Black, 2008). Alpha-2 adrenergic agonists may cause hypotension and bradycardia and therefore should be used with caution in hemodynamically unstable patients (Keating, 2015; Oyler et al., 2015). Because of these AEs, clonidine and dexmedetomidine require increased monitoring and should be administered only by experienced providers. Alpha-2 adrenergic agonists may also reduce hyperadrenergic states and provide comfort for patients experiencing opioid withdrawal (Gowing, Farrell, Ali, & White, 2014; Panzer et al., 2011).
Techniques Requiring Additional Support
Ketamine inhibits neuropathic and nociceptive pain signaling and promotes anesthesia (at higher doses) by binding to the N-methyl-d-aspartate receptor (Arendt-Nielsen et al., 1995; Jennings, Cameron, & Bernard, 2011; Oyler et al., 2015). The drug may decrease pain hypersensitivity and windup pain (i.e., the continuation of pain sensation despite the absence of a stimulus) (Kundra et al., 2013) as well as opioid tolerance (Subramaniam, Subramaniam, & Steinbrook, 2004) and so might be particularly appropriate for patients with long-term opioid use (Goltser, Soleyman-Zomalan, Kresch, & Motov, 2015).
According to reviews, IV ketamine can be safe and effective in the prehospital setting for patients presenting with pain from causes including bone fractures (Jennings et al., 2011), for burn patients (McGuinness et al., 2011), and for analgesia during intubation of patients with acute head injury (Sih, Campbell, Tallon, Magee, & Zed, 2011). Data from two trials, one of which was double-blind, showed similar trauma pain relief for ketamine and morphine (Miller, Schauer, Ganem, & Bebarta, 2015; Tran et al., 2014). A meta-analysis demonstrated that ketamine reduced the amount of opioid used versus placebo after surgery (Laskowski et al., 2011), and an open-label study showed superior analgesia for out-of-hospital trauma pain when IV ketamine was added to IV morphine therapy compared with IV morphine therapy alone (Jennings et al., 2012). In addition, a double-blind study demonstrated a benefit of oral ketamine and midazolam versus oral acetaminophen, midazolam, plus codeine in pediatric burn patients (Norambuena et al., 2013).
Ketamine requires monitoring and nursing support to address potential postdose agitation and hallucinations as well as elevations in heart rate and blood pressure (Miller et al., 2015; Polomano et al., 2013; Tran et al., 2014), and administration is best performed by providers familiar with its use. In summary, ketamine can play an important role in multimodal therapy if the required medical and nursing support is available.
The application of local anesthetics (e.g., for multiple types of nerve blocks) or a low dose of an opioid (e.g., for epidurals or spinals) near the nerves that transmit a pain signal can be a well-tolerated and effective method of pain control that limits doses of systemic opioids (Choi, Lin, & Gadsden, 2013; Oyler et al., 2015) and is recommended by ICU guidelines (Barr et al., 2013).
Nerve blocks placed near the brachial plexus can provide analgesia for the upper extremity and shoulder, whereas epidurals and transversus abdominis plane (TAP)blocks have been shown to provide effective analgesia after abdominal procedures (Argoff, 2014; Oyler et al., 2015). For patients with traumatic rib fractures, a thoracic epidural is suggested (Barr et al., 2013). If an epidural is contraindicated (e.g., because of infection, coagulopathy, or hemodynamic instability), a paravertebral block may be a similarly effective alternative (Chelly, 2012; Mohta, Ophrii, Sethi, Agarwal, & Jain, 2013; Winters, 2009). Paravertebral blocks have been associated with fewer AEs such as hypotension and respiratory depression than epidurals (Chelly, 2012). Intercostal blocks also have effectively relieved pain after rib fracture (De Cosmo, Aceto, Gualtieri, & Congedo, 2009), and continuous infusion intercostal blocks have been shown to reduce hospitalization time versus continuous epidural infusion (Britt, Sturm, Ricardi, & Labond, 2015).
Nerve blocks placed along the femoral and sciatic nerve distribution can reduce pain in the lower extremities (Oyler et al., 2015). Patients with hip fractures may benefit from femoral nerve blocks, as evidenced by a trial showing reduced pain intensity for ultrasound-guided 3-in-1 femoral nerve blocks in addition to IV morphine versus IV morphine plus placebo (Beaudoin, Haran, & Liebmann, 2013). Fascia iliaca blocks are a type of nerve block for femoral injuries that can be easily performed by emergency medical service personnel (McRae, Bendall, Madigan, & Middleton, 2015; Slagt & van Geffen, 2015). Prehospital patients randomized to a fascia iliaca block achieved greater pain relief than those randomized to IV morphine only (McRae et al., 2015). In a double-blind study of hip fractures in an ED, similar long-term efficacy (up to 8 hr) was achieved for a fascia iliaca block versus an IV NSAID injection (Godoy Monzón, Vazquez, Jauregui, & Iserson, 2010).
Interventional techniques are important additions to multimodal analgesia, but caution must be used with neuraxial procedures in the setting of anticoagulation because of bleeding risk (Choi et al., 2013; Oyler et al., 2015). Use of regional blocks for extremity fractures in patients at risk for compartment syndrome is controversial because of the potential masking of signs associated with this condition; however, there is no definitive correlation between the use of peripheral nerve blocks and delay in the diagnosis of compartment syndrome (Choi et al., 2013). In summary, various effective regional techniques are available for multiple locations of pain. The placement and management of regional blocks/catheters require the expertise of trained professionals who may not be available at all institutions.
Nonpharmacologic approaches may complement drug therapy as part of a multimodal plan to relieve pain (Barr et al., 2013). These approaches tend to be easy to implement and relatively safe (Barr et al., 2013). Nonpharmacologic approaches also assist patients in feeling more involved in their pain management. Many of the studies described below demonstrate the efficacy of nonpharmacologic approaches, but as a caveat, none were double-blind. One rationale for lack of blinding is that appropriate controls such as placebos or sham treatments have not yet been developed for these therapies.
Ice packs are used to reduce swelling/edema and associated pain in a variety of trauma injuries (Berben et al., 2011; Rana et al., 2013). Circulating cold water therapy reduced postoperative fracture pain more than conventional cooling (Rana et al., 2013), and a cold pressure system reduced opioid consumption versus epidural after knee arthroplasty (Holmström & Härdin, 2005). In summary, cryotherapy is a widely accepted adjunctive treatment for trauma injuries.
Distraction techniques (e.g., movies, virtual reality) focus patient attention and limit the nervous system's ability to process pain stimuli (Jeffs et al., 2014). These techniques have been shown to effectively relieve pain in adults (Drahota et al., 2012), and other studies have focused on their efficacy in children and adolescents. Trials during laceration repair for children in the ED (Ha & Kim, 2013) and during physical therapy for children and adolescent burn patients (Schmitt et al., 2011) showed improved pain relief with distraction versus no distraction. Sophisticated multimodal distraction (e.g., educational device, virtual reality) decreased pain intensity relative to standard distraction (e.g., television, videos, stories, toys, soothing) in studies of children or adolescents with burns (Brown, Kimble, Rodger, Ware, & Cuttle, 2014; Jeffs et al., 2014; Kipping, Rodger, Miller, & Kimble, 2012; Miller, Rodger, Kipping, & Kimble, 2011). An abundance of evidence supports the use of distraction techniques for reducing pain and potentially reducing the need for anxiolytics and opioids, particularly after burns (Drahota et al., 2012; Jeffs et al., 2014).
Breathing and Relaxation
Relaxation techniques such as breathing exercises can be effective at decreasing pain and reducing reliance on opioids (Barr et al., 2013; Wong, Chan, & Chair, 2010). A study of patients with bone fractures showed greater pain reduction for the yogic prana energization technique (involving controlled breathing, chanting, and visualization) versus control (Oswal, Nagarathna, Ebnezar, & Nagendra, 2011). Another study demonstrated decreased pain with activity for a mind-body skills–based intervention plus standard of care versus only standard of care (Vranceanu et al., 2015). In a trial of patients with musculoskeletal trauma, an educational intervention involving training on breathing relaxation decreased pain levels more than usual care involving no educational intervention (Wong et al., 2010). Relaxation techniques are simple and effective nonpharmacologic options to complement pharmacologics.
Acupuncture is hypothesized to provide analgesia via central mechanisms by stimulating high-threshold, small-diameter nerves that modulate endogenous opioid pathways (Wong, Cheuk, Lee, & Chu, 2013). However, a systematic review concluded that the efficacy and safety of acupuncture (including scalp, body, auricular, tongue, injection, and electroacupuncture) for traumatic brain injury are not strongly supported on the basis of the quality of the studies identified (Wong et al., 2013). Variations of the technique may be appropriate for rib fractures; in one trial, pain relief was more effective with filiform needles than with thumbtack intradermal needles during deep breathing, coughing, and turning (Ho et al., 2014). Acupuncture is a nonpharmacologic technique with a long history of use to relieve pain, requires specialized practitioners, and has limited recent evidence of its efficacy.
Trauma-related injuries are commonly associated with pain and are often treated with opioids as first-line therapy. Because of the safety concerns associated with opioids, particularly those relating to respiratory depression and misuse and abuse with long-term use, there is a need for opioid-sparing, multimodal therapy for trauma pain. In multimodal analgesia, opioid and nonopioid medications are administered to achieve the safest, most effective pain therapy with additive and synergistic effects; opioid-sparing strategies minimize the dose of opioids administered to reduce safety concerns. This review summarizes results from a literature search of various pharmacologic and nonpharmacologic options for use in opioid-sparing, multimodal trauma pain management. The literature search was limited to the last 5 years, though older articles were included at the authors' discretion; the information and recommendations are not meant to be exhaustive. The review focuses primarily on pain management during hospitalization, with a plan for appropriate weaning or tapering of analgesics at discharge, after which the analgesic regimen will be managed by the primary care physician or surgical team.
Many pharmacologics reviewed have broad indications for the treatment of pain, but several drugs have more limited indications. To disclose potential off-label discussions in this review, meloxicam is indicated for types of arthritis but not pain in general (Boehringer Ingelheim, 2012), gabapentin for postherpetic neuralgia but not other neuropathic pain (Pfizer, 2015b), pregabalin for spinal injuries but not other sources of trauma (Pfizer, 2016), clonidine for hypertension but not pain or opioid withdrawal (Boehringer Ingelheim, 2011), dexmedetomidine for sedation but not pain (HQ Specialty Pharma, 2015), ketamine for burn dressing changes but not other trauma applications (JHP Pharmaceuticals, 2012), and opioid epidural for postsurgical pain but not broader trauma indications (JHP Pharmaceuticals, 2012).
On the basis of its long history of efficacy and safety (Oyler et al., 2015; Viscusi et al., 2012), acetaminophen may be considered a first-line analgesic in trauma patients. Pharmacokinetic data imply a more rapid onset of action as well as a potentially decreased risk of hepatotoxicity for IV acetaminophen versus the oral route, though the clinical relevance of this difference has yet to be clearly established. Available data and clinical experience support the use of the drug for initial trauma pain. Nonsteroidal anti-inflammatory drugs are also first-line agents for trauma pain with demonstrated efficacy across multiple routes of administration (e.g., oral, intramuscular, IV). The relationship between NSAIDs and bone healing is controversial; therefore, the lowest effective dose of NSAIDs should be administered for the shortest amount of time in patients with fractures. Intravenous acetaminophen and NSAIDs may be especially useful for patients who are nauseated or unable to receive medication by mouth (e.g., in the perioperative period or ICU setting), though these are not the only trauma patients likely to benefit from nonoral routes.
Beyond acetaminophen and NSAIDs, additional nonopioids are important options for trauma pain management. Topical local anesthetics are effective for targeted pain relief, especially for neuropathic pain associated with trauma. Gabapentinoids should be considered for opioid-sparing therapy to treat neuropathic and postoperative pain. Muscle relaxants are used to reduce pain associated with muscle spasms, and alpha-2 adrenergic agonists are opioid-sparing analgesics that also have sedative and anxiolytic properties. Institutions with personnel trained to administer ketamine and regional techniques (e.g., epidural; paravertebral, femoral nerve, and fascia iliaca blocks) can also utilize these effective interventions to reduce the need for systemic opioids.
Nonpharmacologic options complement drug therapy to achieve the most comprehensive multimodal analgesia. Cryotherapy, distraction techniques, breathing and relaxation, and acupuncture may be appropriate as safe adjunctive therapy for pain associated with many traumas. Further studies are needed on methods for safely and effectively combining pharmacologic and nonpharmacologic analgesics in multimodal therapy.
Patients who are receiving long-term opioid therapy for chronic pain may particularly benefit from multimodal therapy. Guidelines on postoperative pain management (Chou et al., 2016) suggest that providers conduct a preoperative evaluation to document opioid use, provide education regarding opioids before surgery, and recognize that postoperative pain may be challenging to treat and may require increased doses of pain medications in patients who receive long-term opioid therapy. To achieve sufficient analgesia in postoperative patients with chronic pain, these guidelines propose considering the following measures: consultation with a pain specialist (and perhaps a behavioral/addiction specialist) for complex cases, nonopioid systemic medications, nonpharmacologic interventions, local anesthetic–based analgesic techniques, and patient-controlled analgesia. Instructions on tapering opioids after discharge are recommended. As a caveat, these guidelines were developed for postoperative pain instead of trauma pain, but the authors believe that the principles may also apply to the trauma setting.
If one multimodal treatment plan does not effectively relieve pain, another may be warranted. As drivers of patient assessment and intervention, nurses are in a unique position to advocate for appropriate analgesia as a patient's needs change over time. The authors also encourage nurses to involve patients in treatment decisions and manage patient expectations to enhance satisfaction. Nurses who stay informed of current pain management strategies and are aware of evidence and resources that support multimodal treatment options are best prepared to provide effective patient care. Nurses can educate staff and patients who may be unaware of the benefits attributable to opioid-sparing multimodal therapy, such as reducing the side effects of opioids (e.g., sedation, nausea, constipation) as well as mitigating the risks of opioid abuse and dependence. Nurses are encouraged to initiate, participate in, and share results from quality improvement projects related to pain management strategies. The future of trauma pain management involves comprehensive, opioid-sparing, patient-focused analgesic strategies, with nurses playing a key role.
The management of trauma pain by multimodal and opioid-sparing therapy (i.e., including both opioids and nonopioids) is increasingly supported by clinical studies and recommended by pain specialists. On the basis of a literature search of recent trauma studies and the authors' clinical experience, oral acetaminophen, IV acetaminophen, and NSAIDs appear to be safe and effective analgesics for trauma pain when contraindications are considered. Topical local anesthetics show limited evidence of efficacy. Gabapentinoids are appropriate to treat neuropathic pain associated with trauma, muscle relaxants can address painful spasms, and alpha-2 adrenergic agonists can be used to treat pain and opioid withdrawal. Ketamine and regional techniques should be considered in institutions that support their use. Nonpharmacologic techniques (e.g., cryotherapy, distraction techniques, breathing and relaxation, acupuncture) may also contribute to a comprehensive approach to trauma pain management. Reviewed data support the opioid-sparing properties of acetaminophen, NSAIDs, gabapentinoids, alpha-2 adrenergic agonists, ketamine, regional techniques, and nonpharmacologic techniques. Nurses play an important role in managing patient expectations as well as optimizing and individualizing pain management in trauma patients.
- Traditionally, trauma pain management has relied heavily on opioids, which are associated with safety concerns. Therefore, emerging treatment strategies should minimize the dose of opioids and involve the administration of other analgesics to optimize safe and effective pain control.
- Medications that can be used to minimize the dose of opioids and enhance pain relief include acetaminophen, NSAIDs, anticonvulsants, muscle relaxants, and alpha-2 adrenergic agonists. Ketamine and regional techniques are also effective for pain management but require special education and training of physician and nursing staff as well as additional patient monitoring. Nonpharmacologic treatments that can be used with pain medications to improve pain relief include cryotherapy, distraction techniques, breathing and relaxation, and acupuncture.
- Nurses play critical roles in assessing patients' trauma pain, administering agents and techniques to relieve pain, monitoring for side effects/safety concerns, and researching improvements in pain management.
Authors thank Mallinckrodt Pharmaceuticals for commercial support and Carolyn Green, PhD, of MedLogix Communications, LLC (Schaumburg, Illinois), for technical and editorial support. None of the authors received direct compensation from a pharmaceutical company, device company, or other agency for their contributions to the development of this manuscript.
Aldington D. J., McQuay H. J., Moore R. A. (2011). End-to-end military pain management. Philosophical Transactions of the Royal Society of London, 366(1562), 268–275. doi: 10.1098/rstb.2010.0214
American Society of Anesthesiologists Task Force on Acute Pain Management. (2012). 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, 116(2), 248–273. doi: 10.1097/ALN.0b013e31823c1030
Arendt-Nielsen L., Petersen-Felix S., Fischer M., Bak P., Bjerring P., Zbinden A. M. (1995). The effect of N
-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: A placebo-controlled experimental human study. Anesthesia and Analgesia, 81(1), 63–68.
Argoff C. E. (2014). Recent management advances in acute postoperative pain. Pain Practice, 14(5), 477–487. doi: 10.1111/papr.12108
Barr J., Fraser G. L., Puntillo K., Ely E. W., Gélinas C., Dasta J. F., Jaeschke R.; American College of Critical Care Medicine. (2013). Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Critical Care Medicine, 41(1), 263–306. doi: 10.1097/CCM.0b013e3182783b72
Beaudoin F. L., Haran J. P., Liebmann O. (2013). A comparison of ultrasound-guided three-in-one femoral nerve block versus parenteral opioids alone for analgesia in emergency department patients with hip fractures: A randomized controlled trial. Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine, 20(6), 584–591. doi: 10.1111/acem.12154
Beaudoin F. L., Straube S., Lopez J., Mello M. J., Baird J. (2014). Prescription opioid misuse among ED patients discharged with opioids. The American Journal of Emergency Medicine, 32(6), 580–585. doi: 10.1016/j.ajem.2014.02.030
Berben S. A., Schoonhoven L., Meijs T. H., van Vugt A. B., van Grunsven P. M. (2011). Prevalence and relief of pain in trauma
patients in emergency medical services. The Clinical Journal of Pain, 27(7), 587–592. doi: 10.1097/AJP.0b013e3182169036
Bernard J. M., Hommeril J. L., Passuti N., Pinaud M. (1991). Postoperative analgesia by intravenous clonidine. Anesthesiology, 75(4), 577–582.
Boehringer Ingelheim. (2011). Catapres [package insert]. Ridgefield, CT: Author.
Boehringer Ingelheim. (2012). Mobic [package insert]. Ridgefield, CT: Author.
Bondarsky E. E., Domingo A. T., Matuza N. M., Taylor M. B., Thode H. C. Jr., Singer A. J. (2013). Ibuprofen vs acetaminophen vs their combination in the relief of musculoskeletal pain in the ED: A randomized, controlled trial. The American Journal of Emergency Medicine, 31(9), 1357–1360. doi: 10.1016/j.ajem.2013.06.007
Britt T., Sturm R., Ricardi R., Labond V. (2015). Comparative evaluation of continuous intercostal nerve block or epidural analgesia on the rate of respiratory complications, intensive care unit, and hospital stay following traumatic rib fractures: A retrospective review. Local and Regional Anesthesia, 8, 79–84. doi: 0.2147/LRA.S80498
Brown N. J., Kimble R. M., Rodger S., Ware R. S., Cuttle L. (2014). Play and heal: Randomized controlled trial of Ditto™ intervention efficacy on improving re-epithelialization in pediatric burns. Burns: Journal of the International Society for Burn Injuries, 40(2), 204–213. doi: 10.1016/j.burns.2013.11.024
Browne A. L., Andrews R., Schug S. A., Wood F. (2011). Persistent pain outcomes and patient satisfaction with pain management after burn injury. The Clinical Journal of Pain, 27(2), 136–145. doi: 10.1097/AJP.0b013e3181f7f9bb
Chelly J. E. (2012). Paravertebral blocks. Anesthesiology Clinics, 30(1), 75–90. doi: 10.1016/j.anclin.2011.12.001
Cherpitel C. J., Ye Y., Bond J., Borges G., Monteiro M., Chou P., Hao W. (2015). Alcohol attributable fraction for injury morbidity from the dose–response relationship of acute alcohol consumption: Emergency department data from 18 countries. Addiction (Abingdon, England), 110(11), 1724–1732. doi: 10.1111/add.13031
Cho C. H., Song K. S., Min B. W., Lee K. J., Ha E., Lee Y. C., Lee Y. K. (2011). Multimodal approach to postoperative pain control in patients undergoing rotator cuff repair. Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA, 19(10), 1744–1748. doi: 10.1007/s00167-010-1294-y
Choi J. J., Lin E., Gadsden J. (2013). Regional anesthesia for trauma
outside the operating theatre. Current Opinion in Anaesthesiology, 26(4), 495–500. doi: 10.1097/ACO.0b013e3283625ce3
Chou R., Fanciullo G. J., Fine P. G., Adler J. A., Ballantyne J. C., Davies P., Miaskowski C.; American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. (2009). Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. The Journal of Pain: Official Journal of the American Pain Society, 10(2), 113–130. doi: 10.1016/j.jpain.2008.10.008
Chou R., Gordon D. B., de Leon-Casasola O. A., Rosenberg J. M., Bickler S., Brennan T., Wu C. L. (2016). 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. The Journal of Pain: Official Journal of the American Pain Society, 17(2), 131–157. doi: 10.1016/j.jpain.2015.12.008
Craig M., Jeavons R., Probert J., Benger J. (2012). Randomised comparison of intravenous paracetamol and intravenous morphine for acute traumatic limb pain in the emergency department. Emergency Medicine Journal: EMJ, 29(1), 37–39. doi: 10.1136/emj.2010.104687
De Cosmo G., Aceto P., Gualtieri E., Congedo E. (2009). Analgesia in thoracic surgery: Review. Minerva Anestesiologica, 75(6), 393–400.
De Kock M. F., Lavand'homme P. M. (2007). The clinical role of NMDA receptor antagonists for the treatment of postoperative pain. Best Practice & Research: Clinical Anaesthesiology, 21(1), 85–98. doi: 10.1016/j.bpa.2006.12.006
Desai C., Wood F. M., Schug S. A., Parsons R. W., Fridlender C., Sunderland V. B. (2014). Effectiveness of a topical local anaesthetic spray as analgesia for dressing changes: A double-blinded randomised pilot trial comparing an emulsion with an aqueous lidocaine formulation. Burns: Journal of the International Society for Burn Injuries, 40(1), 106–112. doi: 10.1016/j.burns.2013.05.013
Dijkstra B. M., Berben S. A., van Dongen R. T., Schoonhoven L. (2014). Review on pharmacological pain management in trauma
patients in (pre-hospital) emergency medicine in the Netherlands. European Journal of Pain (London, England), 18(1), 3–19. doi: 10.1002/j.1532-2149.2013.00337.x
D'Mello R., Dickenson A. H. (2008). Spinal cord mechanisms of pain. British Journal of Anaesthesia, 101(1), 8–16. doi: 10.1093/bja/aen088
Dodwell E. R., Latorre J. G., Parisini E., Zwettler E., Chandra D., Mulpuri K., Snyder B. (2010). NSAID exposure and risk of nonunion: A meta-analysis of case–control and cohort studies. Calcified Tissue International, 87(3), 193–202. doi: 10.1007/s00223-010-9379-7
Drahota A., Ward D., Mackenzie H., Stores R., Higgins B., Gal D., Dean T. P. (2012). Sensory environment on health-related outcomes of hospital patients. The Cochrane Database of Systematic Reviews, 3, CD005315. doi: 10.1002/14651858.CD005315.pub2
EKR Therapeutics. (2008). Depodur [package insert]. Bedminster, NJ: Author.
Fabricant L., Ham B., Mullins R., Mayberry J. (2013). Prolonged pain and disability are common after rib fractures. American Journal of Surgery, 205(5), 511–515; discussion 515–516. doi: 10.1016/j.amjsurg.2012.12.007
Garg N., Panda N. B., Gandhi K. A., Bhagat H., Batra Y. K., Grover V. K., Chhabra R. (2016). Comparison of small dose ketamine and dexmedetomidine infusion for postoperative analgesia in spine surgery: A prospective randomized double-blind placebo controlled study. Journal of Neurosurgical Anesthesiology, 28(1), 27–31. doi: 10.1097/ANA.0000000000000193
Garra G., Singer A. J., Taira B. R., Chohan J., Cardoz H., Chisena E., Thode H. C. Jr. (2010). Validation of the Wong-Baker FACES Pain Rating Scale in pediatric emergency department patients. Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine, 17(1), 50–54. doi: 10.1111/j.1553-2712.2009.00620.x
Gausche-Hill M., Brown K. M., Oliver Z. J., Sasson C., Dayan P. S., Eschmann N. M., Lang E. S. (2014). An evidence-based guideline for prehospital analgesia in trauma
. Prehospital Emergency Care: Official Journal of the National Association of EMS Physicians and the National Association of State EMS Directors, 18(Suppl. 1), 25–34. doi: 10.3109/10903127.2013.844873
Gélinas C. (2016). Pain assessment in the critically ill adult: Recent evidence and new trends. Intensive and Critical Care Nursing, 34, 1–11. doi: 10.1016/j.iccn.2016.03.001
Georgy E. E., Carr E. C., Breen A. C. (2011). Met or matched expectations: What accounts for a successful back pain consultation in primary care? Health Expectations, 16(2), 143–154. doi: 10.1111/j.1369-7625.2011.00706.x
Gilron I. (2007). Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: Current evidence and future directions. Current Opinion in Anaesthesiology, 20(5), 456–472. doi: 10.1097/ACO.0b013e3282effaa7
Gimbel J., Linn R., Hale M., Nicholson B. (2005). Lidocaine patch treatment in patients with low back pain: Results of an open-label, nonrandomized pilot study. American Journal of Therapeutics, 12(4), 311–319.
Godoy Monzón D., Vazquez J., Jauregui J. R., Iserson K. V. (2010). Pain treatment in post-traumatic hip fracture in the elderly: Regional block vs. systemic non-steroidal analgesics. International Journal of Emergency Medicine, 3(4), 321–325. doi: 10.1007/s12245-010-0234-4
Goltser A., Soleyman-Zomalan E., Kresch F., Motov S. (2015). Short (low-dose) ketamine infusion for managing acute pain in the ED: Case-report series. The American Journal of Emergency Medicine, 33(4), 601.e5–601.e7. doi: 10.1016/j.ajem.2014.09.029
Gottschalk A., Smith D. S. (2001). New concepts in acute pain therapy: Preemptive analgesia. American Family Physician, 63(10), 1979–1984.
Gowing L., Farrell M. F., Ali R., White J. M. (2014). Alpha2-adrenergic agonists for the management of opioid withdrawal. The Cochrane Database of Systematic Reviews, 3, CD002024. doi: 10.1002/14651858.CD002024.pub4
Graff J., Skarke C., Klinkhardt U., Watzer B., Harder S., Seyberth H., Nüsing R. M. (2007). Effects of selective COX-2 inhibition on prostanoids and platelet physiology in young healthy volunteers. Journal of Thrombosis and Haemostasis, 5(12), 2376–2385. doi: 10.1111/j.1538-7836.2007.02782.x
Gray P., Kirby J., Smith M. T., Cabot P. J., Williams B., Doecke J., Cramond T. (2011). Pregabalin in severe burn injury pain: A double-blind, randomised placebo-controlled trial. Pain, 152(6), 1279–1288. doi: 10.1016/j.pain.2011.01.055
Gregoire N., Hovsepian L., Gualano V., Evene E., Dufour G., Gendron A. (2007). Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose. Clinical Pharmacology and Therapeutics, 81(3), 401–405. doi: 10.1038/sj.clpt.6100064
Griffin M. L., Bennet H. E., Fitzmaurice G. M., Hill K. P., Provost S. E., Weiss R. D. (2015). Health-related quality of life among prescription opioid-dependent patients: Results from a multi-site study. The American Journal on Addictions, 24(4), 308–314. doi: 10.1111/ajad.12188
Guy S., Mehta S., Leff L., Teasell R., Loh E. (2014). Anticonvulsant medication use for the management of pain following spinal cord injury: Systematic review and effectiveness analysis. Spinal Cord, 52(2), 89–96. doi: 10.1038/sc.2013.146
Ha Y. O., Kim H. S. (2013). The effects of audiovisual distraction on children's pain during laceration repair. International Journal of Nursing Practice, 19(Suppl. 3), 20–27. doi: 10.1111/ijn.12165
Higgins D. M., Kerns R. D., Brandt C. A., Haskell S. G., Bathulapalli H., Gilliam W., Goulet J. L. (2014). Persistent pain and cormorbidity among Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans. Pain Medicine, 15(5), 782–790. doi: 10.1111/pme.12388
Hjermstad M. J., Fayers P. M., Haugen D. F., Caraceni A., Hanks G. W., Loge J. H.; & European Palliative Care Research Collaborative (EPCRC). (2011). Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: A systematic literature review. Journal of Pain and Symptom Management, 41(6), 1073–1093. doi: 10.1016/j.jpainsymman.2010.08.016
Ho H. Y., Chen C. W., Li M. C., Hsu Y. P., Kang S. C., Liu E. H., Lee K. H. (2014). A novel and effective acupuncture modality as a complementary therapy to acute pain relief in inpatients with rib fractures. Biomedical Journal [electronic resource], 37(3), 147–155. doi: 10.4103/2319-4170.117895
Holmström A., Härdin B. C. (2005). Cryo/cuff compared to epidural anesthesia after knee unicompartmental arthroplasty: A prospective, randomized, and controlled study of 60 patients with a 6-week follow-up. The Journal of Arthroplasty, 20(3), 316–321. doi: http://dx.doi.org/10.1016/j.arth.2004.09.043
HQ Specialty Pharma. (2015). Dexmedetomidine hydrochloride injection [package insert]. Paramus, NJ: Author.
Ingalls N. K., Horton Z. A., Bettendorf M., Frye I., Rodriguez C. (2010). Randomized, double-blind, placebo-controlled trial using lidocaine patch 5% in traumatic rib fractures. Journal of the American College of Surgeons, 210(2), 205–209. doi: 10.1016/j.jamcollsurg.2009.10.020
Jarzyna D., Jungquist C. R., Pasero C., Willens J. S., Nisbet A., Oakes L., Polomano R. C. (2011). American Society for Pain Management Nursing guidelines on monitoring for opioid-induced sedation and respiratory depression. Pain Management Nursing: Official Journal of the American Society of Pain Management Nurses, 12(3), 118–145.e110. doi: 10.1016/j.pmn.2011.06.008
Jeffs D., Dorman D., Brown S., Files A., Graves T., Kirk E., Swearingen C. J. (2014). Effect of virtual reality on adolescent pain during burn wound care. Journal of Burn Care and Research: Official Publication of the American Burn Association, 35(5), 395–408. doi: 10.1097/BCR.0000000000000019
Jenkins M. G., Murphy D. J., Little C., McDonald J., McCarron P. A. (2014). A non-inferiority randomized controlled trial comparing the clinical effectiveness of anesthesia obtained by application of a novel topical anesthetic putty with the infiltration of lidocaine for the treatment of lacerations in the emergency department. Annals of Emergency Medicine, 63(6), 704–710. doi: 10.1016/j.annemergmed.2013.12.012
Jennings P. A., Cameron P., Bernard S. (2011). Ketamine as an analgesic in the pre-hospital setting: A systematic review. Acta Anaesthesiologica Scandinavica, 55(6), 638–643. doi: 10.1111/j.1399-6576.2011.02446.x
Jennings P. A., Cameron P., Bernard S., Walker T., Jolley D., Fitzgerald M., Masci K. (2012). Morphine and ketamine is superior to morphine alone for out-of-hospital trauma
analgesia: A randomized controlled trial. Annals of Emergency Medicine, 59(6), 497–503. doi: 10.1016/j.annemergmed.2011.11.012
JHP Pharmaceuticals. (2012). Ketalar [package insert]. Rochester, MI: Author.
Jones P., Lamdin R. (2010). Oral cyclo-oxygenase 2 inhibitors versus other oral analgesics for acute soft tissue injury: Systematic review and meta-analysis. Clinical Drug Investigation, 30(7), 419–437. doi: 10.2165/11533350-000000000-00000
Katz N. P., Adams E. H., Chilcoat H., Colucci R. D., Comer S. D., Goliber P., Weiss R. (2007). Challenges in the development of prescription opioid abuse-deterrent formulations. The Clinical Journal of Pain, 23(8), 648–660. doi: 10.1097/AJP.0b013e318125c5e8
Keating G. M. (2015). Dexmedetomidine: A review of its use for sedation in the intensive care setting. Drugs, 75(10), 1119–1130. doi: 10.1007/s40265-015-0419-5
Keene D. D., Rea W. E., Aldington D. (2011). Acute pain management in trauma
(London, England), 13(3), 167–179. doi: 10.1177/1460408611400813
Kehlet H., Dahl J. B. (1993). The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesthesia and Analgesia, 77(5), 1048–1056.
Khwaja S. M., Minnerop M., Singer A. J. (2010). Comparison of ibuprofen, cyclobenzaprine or both in patients with acute cervical strain: A randomized controlled trial. CJEM, 12(1), 39–44.
Kipping B., Rodger S., Miller K., Kimble R. M. (2012). Virtual reality for acute pain reduction in adolescents undergoing burn wound care: A prospective randomized controlled trial. Burns: Journal of the International Society for Burn Injuries, 38(5), 650–657. doi: 10.1016/j.burns.2011.11.010
Kuehl K., Carr W., Yanchick J., Magelli M., Rovati S. (2011). Analgesic efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) in minor soft tissue injury. International Journal of Sports Medicine, 32(8), 635–643. doi: 10.1055/s-0031-1275359
Kundra P., Velayudhan S., Krishnamachari S., Gupta S. L. (2013). Oral ketamine and dexmedetomidine in adults' burns wound dressing—A randomized double blind cross over study. Burns: Journal of the International Society for Burn Injuries, 39(6), 1150–1156. doi: 10.1016/j.burns.2013.02.012
Laskowski K., Stirling A., McKay W. P., Lim H. J. (2011). A systematic review of intravenous ketamine for postoperative analgesia. Canadian Journal of Anaesthesia, 58(10), 911–923. doi: 10.1007/s12630-011-9560-0
Likar R., Kager I., Obmann M., Pipam W., Sittl R. (2012). Treatment of localized neuropathic pain after disk herniation with 5% lidocaine medicated plaster. International Journal of General Medicine, 5, 689–692. doi: 10.2147/IJGM.S32314
Macintyre P. E., Huxtable C. A., Flint S. L., Dobbin M. D. (2014). Costs and consequences: A review of discharge opioid prescribing for ongoing management of acute pain. Anaesthesia and Intensive Care, 42(5), 558–574.
Malchow R. J., Black I. H. (2008). The evolution of pain management in the critically ill trauma
patient: Emerging concepts from the global war on terrorism. Critical Care Medicine, 36(7, Suppl.), S346–S357. doi: 10.1097/CCM.0b013e31817e2fc9
Mazer-Amirshahi M., Mullins P. M., Rasooly I., van den Anker J., Pines J. M. (2014). Rising opioid prescribing in adult U.S. emergency department visits: 2001–2010. Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine, 21(3), 236–243. doi: 10.1111/acem.12328
McGuinness S. K., Wasiak J., Cleland H., Symons J., Hogan L., Hucker T., Mahar P. D. (2011). A systematic review of ketamine as an analgesic agent in adult burn injuries. Pain Medicine (Malden, Mass.), 12(10), 1551–1558. doi: 10.1111/j.1526-4637.2011.01220.x
McGreevy K., Bottros M. M., Raja S. N. (2011). Preventing chronic pain following acute pain: Risk factors, preventive strategies, and their efficacy. European Journal of Pain Supplements, 5(2), 365–372. doi: 10.1016/j.eujps.2011.08.013
McKeown J. L. (2015). Pain management issues for the geriatric surgical patient. Anesthesiology Clinics, 33(3), 563–576. doi: 10.1016/j.anclin.2015.05.010
McRae P. J., Bendall J. C., Madigan V., Middleton P. M. (2015). Paramedic-performed fascia iliaca compartment block for femoral fractures: A controlled trial. The Journal of Emergency Medicine, 48(5), 581–589. doi: 10.1016/j.jemermed.2014.12.016
Melemeni A., Staikou C., Fassoulaki A. (2007). Gabapentin for acute and chronic post-surgical pain. Signa Vitae, 2(Suppl. 1), S42–S51.
Miller J. P., Schauer S. G., Ganem V. J., Bebarta V. S. (2015). Low-dose ketamine vs morphine for acute pain in the ED: A randomized controlled trial. The American Journal of Emergency Medicine, 33(3), 402–408. doi: 10.1016/j.ajem.2014.12.058
Miller K., Rodger S., Kipping B., Kimble R. M. (2011). A novel technology approach to pain management in children with burns: A prospective randomized controlled trial. Burns: Journal of the International Society for Burn Injuries, 37(3), 395–405. doi: 10.1016/j.burns.2010.12.008
Mohta M., Ophrii E. L., Sethi A. K., Agarwal D., Jain B. K. (2013). Continuous paravertebral infusion of ropivacaine with or without fentanyl for pain relief in unilateral multiple fractured ribs. Indian Journal of Anaesthesia, 57(6), 555–561. doi: 10.4103/0019-5049.123327
National Center for Health Statistics, & Ambulatory and Hospital Care Statistics Branch. (n.d.). National hospital ambulatory medical care survey: 2011 Emergency department summary tables. Retrieved from http://www.cdc.gov/nchs/data/ahcd/nhamcs_emergency/2011_ed_web_tables.pdf
Nikolajsen L., Finnerup N. B., Kramp S., Vimtrup A. S., Keller J., Jensen T. S. (2006). A randomized study of the effects of gabapentin on postamputation pain. Anesthesiology, 105(5), 1008–1015.
Norambuena C., Yañez J., Flores V., Puentes P., Carrasco P., Villena R. (2013). Oral ketamine and midazolam for pediatric burn patients: A prospective, randomized, double-blind study. Journal of Pediatric Surgery, 48(3), 629–634. doi: 10.1016/j.jpedsurg.2012.08.018
Ong C. K., Seymour R. A., Lirk P., Merry A. F. (2010). Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: A qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesthesia and Analgesia, 110(4), 1170–1179. doi: 10.1213/ANE.0b013e3181cf9281
Ossipov M. H., Dussor G. O., Porreca F. (2010). Central modulation of pain. The Journal of Clinical Investigation, 120(11), 3779–3787. doi: 10.1172/JCI43766
Oswal P., Nagarathna R., Ebnezar J., Nagendra H. R. (2011). The effect of add-on yogic prana energization technique (YPET) on healing of fresh fractures: A randomized control study. Journal of Alternative and Complementary Medicine (New York, N.Y.), 17(3), 253–258. doi: 10.1089/acm.2010.0001
Oyler D. R., Parli S. E., Bernard A. C., Chang P. K., Procter L. D., Harned M. E. (2015). Nonopioid management of acute pain associated with trauma
: Focus on pharmacologic options. The Journal of Trauma
and Acute Care Surgery, 79(3), 475–483. doi: 10.1097/TA.0000000000000755
Panzer O., Moitra V., Sladen R. N. (2011). Pharmacology of sedative-analgesic agents: Dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral Mu antagonists. Anesthesiology Clinics, 29(4), 587–605, vii. doi: 10.1016/j.anclin.2011.09.002
Parsons B., Sanin L., Yang R., Emir B., Juhn M. (2013). Efficacy and safety of pregabalin in patients with spinal cord injury: A pooled analysis. Current Medical Research and Opinion, 29(12), 1675–1683. doi: 10.1185/03007995.2013.834815
Pasero C., McCaffery M. (Eds.). (2011). Pain assessment and pharmacologic management. St. Louis, MO: Mosby Elsevier.
Pfizer. (2015a, November 25). Pfizer reports top-line results from a phase 3 study of LYRICA® (pregabalin) capsules CV in adults with post-traumatic peripheral neuropathic pain [Press release]. Retrieved from http://www.pfizer.com/news/press-release/press-release-detail/pfizer_reports_top_line_results_from_a_phase_3_study_of_lyrica_pregabalin_capsules_cv_in_adults_with_post_traumatic_peripheral_neuropathic_pain
Pfizer. (2015b). Neurontin [package insert]. New York, NY: Author.
Pfizer. (2016). Lyrica [package insert]. New York, NY: Author.
Polomano R. C., Buckenmaier C. C., Kwon K. H., Hanlon A. L., Rupprecht C., Goldberg C., Gallagher R. M. (2013). Effects of low-dose IV ketamine on peripheral and central pain from major limb injuries sustained in combat. Pain Medicine (Malden, Mass.), 14(7), 1088–1100. doi: 10.1111/pme.12094
Poonai N., Bhullar G., Lin K., Papini A., Mainprize D., Howard J., Ali S. (2014). Oral administration of morphine versus ibuprofen to manage postfracture pain in children: A randomized trial. CMAJ: Canadian Medical Association Journal, 186(18), 1358–1363. doi: 10.1503/cmaj.140907
Pountos I., Georgouli T., Calori G. M., Giannoudis P. V. (2012). Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis. The Scientific World Journal [electronic resource], 606404. doi: 10.1100/2012/606404
Rana M., Gellrich N. C., von See C., Weiskopf C., Gerressen M., Ghassemi A., Modabber A. (2013). 3D evaluation of postoperative swelling in treatment of bilateral mandibular fractures using 2 different cooling therapy methods: A randomized observer blind prospective study. Journal of Cranio-maxillofacial Surgery: Official Publication of the European Association for Cranio-Maxillo-Facial Surgery, 41(1), e17-e23. doi: 10.1016/j.jcms.2012.04.002
Reavey D. A., Haney B. M., Atchison L., Anderson B., Sandritter T., Pallotto E. K. (2014). Improving pain assessment in the NICU: A quality improvement project. Adv Neonatal Care, 14(3), 144–153. doi: 10.1097/ANC.0000000000000034
Rimaz S., Alavi C. E., Sedighinejad A., Tolouie M., Kavoosi S., Koochakinejad L. (2012). Effect of gabapentin on morphine consumption and pain after surgical debridement of burn wounds: A double-blind randomized clinical trial study. Archives of Trauma
Research, 1(1), 38–43. doi: 10.5812/atr.5304
Royal M. A., Gosselin N. H., Pan C. P., Mouksassi M. S., Breitmeyer J. B. (2010). Route of administration significantly impacts hepatic acetaminophen exposure. Clinical Pharmacology and Therapeutics, 87(Suppl. 1), S62.
Schmitt Y. S., Hoffman H. G., Blough D. K., Patterson D. R., Jensen M. P., Soltani M., Sharar S. R. (2011). A randomized, controlled trial of immersive virtual reality analgesia, during physical therapy for pediatric burns. Burns: Journal of the International Society for Burn Injuries, 37(1), 61–68. doi: 10.1016/j.burns.2010.07.007
Sih K., Campbell S. G., Tallon J. M., Magee K., Zed P. J. (2011). Ketamine in adult emergency medicine: Controversies and recent advances. The Annals of Pharmacotherapy, 45(12), 1525–1534. doi: 10.1345/aph.1Q370
Singla N. K., Parulan C., Samson R., Hutchinson J., Bushnell R., Beja E. G., Royal M. A. (2012). Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen. Pain Practice: The Official Journal of the World Institute of Pain, 12(7), 523–532. doi: 10.1111/j.1533-2500.2012.00556.x
Slagt C., van Geffen G. J. (2015). Block them when it hurts. Local and Regional Anesthesia, 8, 93–94. doi: 10.2147/LRA.S95699
Smith H. S. (2009). Potential analgesic mechanisms of acetaminophen. Pain Physician, 12(1), 269–280.
Stroud M. W., Bombardier C. H., Dyer J. R., Rimmele C. T., Esselman P. C. (2011). Preinjury alcohol and drug use among persons with spinal cord injury: Implications for rehabilitation. The Journal of Spinal Cord Medicine, 34(5), 461–472. doi: 10.1179/2045772311Y.0000000033
Subramaniam K., Subramaniam B., Steinbrook R. A. (2004). Ketamine as adjuvant analgesic to opioids: A quantitative and qualitative systematic review. Anesthesia and Analgesia, 99(2), 482–495, table of contents. doi: 10.1213/01.ANE.0000118109.12855.07
Toth C. (2010). Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Pain Medicine (Malden, Mass.), 11(3), 456–465. doi: 10.1111/j.1526-4637.2009.00796.x
Tramèr M. R., Williams J. E., Carroll D., Wiffen P. J., Moore R. A., McQuay H. J. (1998). Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain: A qualitative systematic review. Acta Anaesthesiologica Scandinavica, 42(1), 71–79.
Tran K. P., Nguyen Q., Truong X. N., Le V., Le V. P., Mai N., Losvik O. K. (2014). A comparison of ketamine and morphine analgesia in prehospital trauma
care: A cluster randomized clinical trial in rural Quang Tri province, Vietnam. Prehospital Emergency Care: Official Journal of the National Association of EMS Physicians and the National Association of State EMS Directors, 18(2), 257–264. doi: 10.3109/10903127.2013.851307
Trevino C., Harl F., Deroon-Cassini T., Brasel K., Litwack K. (2014). Predictors of chronic pain in traumatically injured hospitalized adult patients. Journal of Trauma
Nursing: The Official Journal of the Society of Trauma
Nurses, 21(2), 50–56. doi: 10.1097/JTN.0000000000000032
Trevino C. M., Essig B., deRoon-Cassini T., Brasel K. (2012). Chronic pain at 4 months in hospitalized trauma
patients: Incidence and life interference. Journal of Trauma
Nursing: The Official Journal of the Society of Trauma
Nurses, 19(3), 154–159. doi: 10.1097/JTN.0b013e318261d304
Tsang K. S., Page J., Mackenney P. (2013). Can intravenous paracetamol reduce opioid use in preoperative hip fracture patients? Orthopedics, 36(2, Suppl.), 20–24. doi: 10.3928/01477447-20130122-53
U.S. Department of Veterans Affairs, U.S. Department of Defense. (2007). VA/DoD clinical practice guideline for rehabilitation of lower limb amputation. Retrieved from http://www.healthquality.va.gov/guidelines/Rehab/amp/amp_v652.pdf
U.S. Food and Drug Administration. (2011). New steps aimed at cutting risks from acetaminophen [Consumer update; updated August 30, 2015]. Retrieved from http://www.fda.gov/forconsumers/consumerupdates/ucm239747.htm
Vadivelu N., Urman R. D., Hines R. L., Hines R. L. (Eds.). (2011). Essentials of pain management. New York, NY: Springer.
van Tulder M. W., Touray T., Furlan A. D., Solway S., Bouter L. M. (2003). Muscle relaxants for non-specific low back pain. The Cochrane Database of Systematic Reviews, 2, CD004252. doi: 10.1002/14651858.CD004252
Viallon A., Marjollet O., Guyomarch P., Robert F., Berger C., Guyomarch S., Bertrand J. C. (2007). Analgesic efficacy of orodispersible paracetamol in patients admitted to the emergency department with an osteoarticular injury. European Journal of Emergency Medicine, 14(6), 337–342. doi: 10.1097/MEJ.0b013e3282703606
Viscusi E. R., Singla N., Gonzalez A., Saad N., Stepanian J. (2012, April). IV acetaminophen improves pain management and reduces opioid requirements in surgical patients: A review of the clinical data and case-based presentations [Special report]. Anesthesiology News, 1–8. Retrieved from http://www.anesthesiologynews.com/download/SR122_WM.pdf
Vokoun E. S. (2015). Rationale for use of intravenous acetaminophen in special operations medicine. Journal of Special Operations Medicine: A Peer Reviewed Journal for SOF Medical Professionals, 15(2), 71–73.
Vranceanu A. M., Hageman M., Strooker J., ter Meulen D., Vrahas M., Ring D. (2015). A preliminary RCT of a mind body skills based intervention addressing mood and coping strategies in patients with acute orthopaedic trauma
. Injury, 46(4), 552–557. doi: 10.1016/j.injury.2014.11.001
Waldman N., Densie I. K., Herbison P. (2014). Topical tetracaine used for 24 hours is safe and rated highly effective by patients for the treatment of pain caused by corneal abrasions: A double-blind, randomized clinical trial. Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine, 21(4), 374–382. doi: 10.1111/acem.12346
Warner T. D., Mitchell J. A. (2004). Cyclooxygenases: New forms, new inhibitors, and lessons from the clinic. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 18(7), 790–804. doi: 10.1096/fj.03-0645rev
Washington State Agency Medical Directors' Group. (2015). Interagency guideline on prescribing opioids for pain. Retrieved from http://www.agencymeddirectors.wa.gov/Files/2015AMDGOpioidGuideline.pdf
Wibbenmeyer L., Eid A., Liao J., Heard J., Horsfield A., Kral L., Rosenquist R. (2014). Gabapentin is ineffective as an analgesic adjunct in the immediate postburn period. Journal of Burn Care & Research: Official Publication of the American Burn Association, 35(2), 136–142. doi: 10.1097/BCR.0b013e31828a4828
Winters B. A. (2009). Older adults with traumatic rib fractures: An evidence-based approach to their care. Journal of Trauma
Nursing: The Official Journal of the Society of Trauma
Nurses, 16(2), 93–97. doi: 10.1097/JTN.0b013e3181ac9201
Wong E. M., Chan S. W., Chair S. Y. (2010). Effectiveness of an educational intervention on levels of pain, anxiety and self-efficacy for patients with musculoskeletal trauma
. Journal of Advanced Nursing, 66(5), 1120–1131. doi: 10.1111/j.1365-2648.2010.05273.x
Wong V., Cheuk D. K., Lee S., Chu V. (2013). Acupuncture for acute management and rehabilitation of traumatic brain injury. The Cochrane Database of Systematic Reviews, 3, CD007700. doi: 10.1002/14651858.CD007700.pub3
Zare M. A., Ghalyaie A. H., Fathi M., Farsi D., Abbasi S., Hafezimoghadam P. (2014). Oral oxycodone plus intravenous acetaminophen versus intravenous morphine sulfate in acute bone fracture pain control: A double-blind placebo-controlled randomized clinical trial. European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie, 24(7), 1305–1309. doi: 10.1007/s00590-013-1392-x
Zhang J., Ho K. Y., Wang Y. (2011). Efficacy of pregabalin in acute postoperative pain: A meta-analysis. British Journal of Anaesthesia, 106(4), 454–462. doi: 10.1093/bja/aer027
Zink K. A., Mayberry J. C., Peck E. G., Schreiber M. A. (2011). Lidocaine patches reduce pain in trauma
patients with rib fractures. The American Surgeon, 77(4), 438–442.