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This chapter focuses on the pharmacology of the drugs commonly used to provide moderate and deep sedation and their available reversal agents. Intravenous sedative and analgesic drugs should be given in small, incremental doses titrated to desired end points of sedation and analgesia, with adequate time allowed between doses to achieve those effects. Preemptive analgesia is a treatment that is initiated before surgical procedure to reduce sensitization of pain pathways. Potential drug interactions require the clinician providing sedation to be cognizant of potential drug-drug effects, which can lead to morbidity and mortality. Opioids in combination with benzodiazepines provide adequate moderate and/or deep sedation and analgesia for many potentially painful procedures. Other drugs used for deep sedation include propofol, ketamine, dexmedetomidine, and etomidate. Local anesthetics (LA) have the potential to produce deleterious side effects. The choice of a local anesthetic and care in its use are the primary determinants of toxicity.
The diagnosis of neuropathic pain (NP) encompasses a broad array of conditions. For the acute care provider, the goals of NP therapy are to decrease persistent pain and suppress breakthrough pain. One recommended strategy for NP treatment is to begin the therapy simultaneously with two drugs: an analgesic (e.g. mild opioid) and an adjuvant (e.g. antidepressant). Opioid doses in NP may be relatively higher than customary for non-NP indications, and in fact varying types of NP may warrant different opioid dosages. Clinically, patients with allodynia are potential candidates for local anesthetic use. Local anesthetics may also be useful in NP when administered in the form of regional nerve blocks. Since inflammatory mediators sensitize nociception, the anti-inflammatory corticosteroids have been used for NP. Corticosteroids also decrease local edema, thus reducing pressure on peripheral nerves. As dexamethasone has relative few mineralocorticoid effects, it is preferred by many who use corticosteroids in NP.
Treatment decisions regarding diabetic neuropathy (DN) can be made based on useful evidence. Many agents have been assessed for therapy of DN pain, and many have some role in relief of symptoms. The opioid tramadol, which has additional (monoamine-related) mechanisms of analgesia, has particular utility in DN. The tricyclic antidepressants (TCAs) are among the most consistently effective therapy for neuropathic pain. Multiple RCTs have demonstrated the efficacy of the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine in the treatment of DN. A withdrawal syndrome can occur if the SNRIs are abruptly discontinued. Anticonvulsants are a valuable therapeutic option in DN. Pregabalin is effective for DN as well. Topical application of local anesthetics may be useful in patients with focal DN pain. Patch application of lidocaine is known to be effective in DN. Intravenously injected local anesthetics have been reported potentially useful in DN.
Thoracic trauma constitutes 10-15% of all injuries, with rib fractures (RF) being common and painful. The intrathecal injection of morphine has been studied for patients with multiple RFs. If conditions are suitable for their use, the local anesthetics are the most efficacious mechanism for managing RF pain. Local anesthetics (sometimes co-administered with opioids) have also been used by the epidural administration route. This approach is associated with decreased pulmonary morbidity and mortality in patients older than 60 years of age with RF. For the majority of patients with RF, the controversy surrounding NSAIDs and delayed bone fracture healing is relevant. Used in patients with chest wall trauma, epidural analgesia produces pain relief that is superior to that produced by systemic opioids or other local anesthetic approaches. Local anesthetic administration via thoracic paravertebral block entails injecting an agent such as bupivacaine alongside the thoracic vertebrae.
Given the frequency of otitis media (OM) and otitis externa (OE), there is surprisingly little evidence on treating pain associated with these conditions. For both conditions, there can be utility in mechanical interventions. The NSAIDs are typically recommended as first-line treatment, although evidence is sparse. Topically applied local anesthetics, generally benzocaine, are widely used for otalgia. A eutectic mixture of local anesthetics (EMLA), which contains lidocaine and prilocaine, is described as effective for relieving OE pain. Naturopathic topical approaches for OM are found by one investigator to be effective than the topical local anesthetic amethocaine. Trial evidence and reviews find neither antihistamines nor corticosteroids are effective in reducing OM pain. There are no data assessing otalgia relief for systemically administered opioids. However, expert panel evidence supports use of oral agents such as oxycodone or hydrocodone (usually in combination with acetaminophen or ibuprofen) for severe otalgia from either OM or OE.
While mechanical approaches (e.g. splinting) are important in managing sprain, strain, and fracture (SSF) pain, pharmacotherapy retains an important position for orthopedic analgesia. Systemic analgesics used for SSF include acetaminophen (paracetamol), NSAIDs, and opioids. This chapter focuses on systemically active analgesics. Pain relief for SSF can often be facilitated with local or regional injection of local anesthetics. Opioids have long been effectively used for severe SSF pain. Intravenous opioids (e.g. morphine) remain the most effective means for achieving both rapid analgesia and sustained relief (e.g. using patient-controlled analgesia) in most SSF conditions when combined with acetaminophen, the mixed-mechanism opioid tramadol is found to be equally efficacious to hydrocodone for relieving SSF pain. Many combination products are available and often include an opioid and a weaker analgesic such as acetaminophen or aspirin. However, few studies have rigorously evaluated their performance against alternative approaches such as opioid monotherapy.
This chapter separates mechanical strain spinal pain (MSSP) from neck and back pain of other etiologies (e.g. spondylosis, radiculopathy), as there are different therapeutic approaches. The NSAIDs are the mainstay of therapy for non-radiating mechanical back pain, and by extrapolation of evidence from back pain studies, for neck strain. Opioids are the preferred treatment for MSSP in patients who have not responded to, or who cannot take, NSAIDs. Muscle relaxants are often prescribed for sprains and strains of the neck and back. Commonly used muscle relaxants include cyclobenzaprine, orphenadrine, metaxolone, methocarbamol, carisoprodol, and chlorzoxazone. Benzodiazepines have skeletal muscle-relaxing properties, and so this class (most notably diazepam) is occasionally prescribed for MSSP. Trigger point injection with local anesthetics is occasionally effective for some patients with neck or back pain, but injection therapy for MSSP has been insufficiently studied to recommend its routine use.
Available evidence for treating pain caused by mucositis (inflammation of the digestive tract's lining) and stomatitis (mucositis involving the mouth) can be categorized into two general categories, depending on whether or not the stomatitis is related to cancer therapy (either chemo-or radiation therapy). This chapter addresses cancer treatment-associated stomatitis (CTAM). For CTAM that does develop, pain can be severe and opioids are the therapeutic mainstay. In fact, CTAM pain often necessitates IV morphine and even hospitalization and institution of a PCA regimen. Local anesthetics such as tetracaine or lidocaine are often recommended for CTAM, but their utility is not definitively demonstrated. Most of the data dealing with non-CTAM mucositis addresses aphthous ulcer (AU) treatment. Topical sucralfate is an example of an approach that is not successful in CTAM but found useful in AU. The chapter concludes with an overview of the evidence, lesser in quality and quantity, addressing non-CTAM stomatitis.
There are few rigorously conducted clinical trials assessing specific therapy for non-septic bursitis. First-line treatments of non-septic bursitis include NSAIDs, aspiration, and injection therapy with corticosteroids and local anesthetics. Patients receiving oxaprozin showed improved overall function scores on a variety of measures. Results for periarticular inflammation other than bursitis are similar to the findings for bursitis. For patients with shoulder bursitis, oral corticosteroids provide early improvement over placebo, but treatment benefit is lost after the first few weeks of therapy. Many corticosteroids have demonstrated effectiveness for injection of subacromial inflammation. For trochanteric bursitis, studies investigating intrabursal injection of corticosteroids have found efficacy similar to that reported for other bursal injection sites. One long-recognized medication-related etiology of subacromial inflammation is the use of protease inhibitors: indinavir and lamivudine. Given the obvious risks in altering these medication regimens, the ED provider should reduce dosages only after consultation with patients' physicians.
This chapter presents evidence relating to acute therapies for some common arthritic conditions. It discusses the role NSAIDs, acetaminophen (paracetamol), steroids, colchicines, local anesthetics, opioids, and corticotrophin in arthritis. The major arthritides covered are crystal-mediated arthropathy, osteoarthritis (OA), and rheumatoid arthritis (RA). For gouty arthritis, most commentators favor NSAIDs as first-line therapy, but other treatment options (colchicine, corticosteroids, corticotropin [adrenocorticotropic hormone]) are also used. Corticosteroids are generally rated as a second-line therapy for crystal-related arthritis. Most expert reviews and meta-analyses find an unfavorable risk-to-benefit ratio, although some commentators do report occasional utility of the opioids for OA. For patients with OA in the acute care setting, acetaminophen remains a reasonable initial analgesic choice in selected patients. RA and juvenile RA (JRA) are treated with an array of disease-modifying agents that have secondary effects of relieving pain. Systemic or injected glucocorticoids are useful in RA and JRA.
Patients with odontogenic pain (OP) represent a broad spectrum of both disease etiology and severity. This chapter overviews the most important systemic, parenteral, and topical analgesic choices available to the acute care provider trying to relieve OP. NSAIDs are among the most widely used and well-studied drug classes used in management of acute and chronic OP, or odontalgia. Among the NSAIDs demonstrated to provide better pain relief than placebo is parenteral ketorolac. The mixed-mechanism drug tramadol provides pain relief that is partially mediated by opioid receptors. The supraperiosteal infiltration of local anesthetics usually provides suitable anesthesia when OP is emanating from a single maxillary tooth. Injection of local anesthetics is a legitimate, well-studied mechanism for providing relief of OP. In addition to its potential use in alveolar osteitis, benzocaine is efficacious in other causes of OP.
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