Chapter 96. Pain

1. What is your goal of pain therapy?

2. How are you going to “measure” pain?

3. Are you treating multiple pain issues or types of pain?

4. Does this patient have comorbidities that will affect your pain care?

5. What are the most appropriate and effective pain treatment options available?

Taxonomy

Any discussion on the diagnosis and treatment of pain must start with the definition of pain. The International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

Pain can be classified in multiple domains. The first is the classification based on the underlying etiology of the pain. Nociceptive pain refers to the direct tissue injury from a noxious stimulus. Inflammatory pain refers to the release of inflammatory mediators that perpetuate and modulate nociceptive input. Direct injury to nerves results in a third type of pain , neuropathic pain, whereby the nature of sensory transmission is altered and accompanied by pain frequently described as a burning type of pain. Although these are described as discrete types of pain, they more often represent a continuum of the same injury. Surgical incision is a model of nociceptive injury that produces an inflammatory response. Incising the primary nociceptors in the skin with subsequent development of inflammatory neuritis can result in neuropathic pain.

The second domain of classification refers to the anatomic location of pain. In this category, pain can be described as either somatic or visceral. Somatic pain refers to a well-localized sensation related to skin, muscle, and bone, whereby visceral pain is poorly localized and is usually in response to distention of the internal organs such as the colon or small bowel, or compression or inflammatory injury, which occurs in pancreatic cancer or pancreatitis.

The final domain classifies pain based on the temporal nature of the pain. Acute pain usually refers to a neurophysiologic response to a noxious stimulus, a response expected to resolve with completion of wound healing. In contrast, chronic pain persists beyond the expected time course of an acute injury and its repair process. Chronic or persistent pain does not simply suggest that a given time interval has passed. Rather, such a diagnosis implies development of multiple neurophysiologic changes that alter the fundamental balance between noxious stimuli and their inhibitory mechanisms. Such changes occur from the peripheral nerve to the dorsal horn of the spinal column, interneurons throughout the spinal cord, to the thalamus and cortical circuits. These changes ultimately result in remodeling in the organization of the central nervous system.

Evaluation of Pain

Pain is a subjective phenomenon and results from a patient's understanding of the physical and affective impact the sensation has had on them. There are multiple quantitative pain evaluation scales. Although these are subjective reports with no way to verify the answer's “truth,” these scales have been used for decades and correlate well to experimental and clinical pain responsiveness. Although the practitioner must be aware that the patient can manipulate the pain report, it is imperative to first validate the patient's understanding of his or her pain by receiving his or her report with an unbiased view.

The numerical rating scale (NRS) may be the most commonly used tool for the evaluation of pain intensity. Patients are asked to rate their pain on a scale of 0 to10, with 0 translated as “no pain” and 10 the “worst pain imaginable.” Similarly, the visual analog scale (VAS) allows patients to mark a point on a 10-cm line that corresponds to the level of their pain. The 4-point verbal rating scale (VRS) asks patients to categorize their pain as none, mild, moderate, or severe. The VAS and NRS demonstrate excellent agreement, and both offer superior discriminating ability to the categorical VRS.

The above case study involves a patient with dementia, which can pose additional challenges for the evaluation of her pain. Standard pain reporting scales are ineffective for patients who suffer from dementia, who are unconscious, or who are unable to communicate. Pain scales such as MOBID-2, Checklist of Nonverbal Pain Indicators, and Doloplus 2 have each been designed for the patient with dementia or in an assisted living facility. These scales have strong conceptual and psychometric support, however they are an indirect measure of the patient's pain and therefore at risk of the health care providers’ intrinsic biases.

Timing and activity are relevant to the interpretation of pain scores. Reported pain scores may refer to the past hour, 24 hours, week, or month. Average, maximum, and minimum pain scores help ascertain the patient's range of pain. Pain scores may also be described as rest or static versus active or dynamic to correlate the given score with activity level. Pain scores reported by the patient when resting may not reflect pain-based limitations on activity. Because the goal of pain treatment usually includes improvement in mobility or function to decrease thromboembolic and pulmonary complications, addressing only rest/static pain may result in a failure to maximize the benefit of pain control.

The above scales are applied to all types of pain: acute, chronic/persistent, and cancer pain. The added complexity of chronic/persistent or cancer pain can require more multifaceted evaluation tools. Additional pain scales can be administered to these patients to better deliver more targeted pain care, but they will not be discussed as they are beyond the scope of this chapter.

Poorly controlled pain can present through multiple parameters including vital signs and laboratory values, reinforcing the impact of a patient under significant physiologic and psychological stress. Manifestations of this stress can include myocardial ischemia, immunosuppression, impaired wound healing, and thromboembolic events.

Treatment of Pain

Treatment of pain can utilize four primary modalities. These include medications, interventions, behavioral therapies and physical therapy/complementary treatments. This review will focus on the medical and interventional management of pain, although behavior and complementary treatments are essential components of improving the overall pain state in patients with persistent pain.

Systemic Analgesia

Opioids

Opioid medications remain the most common treatment for both acute and chronic/persistent pain. By activating the mu opioid receptor throughout the CNS, opioids modulate the perception and transmission of painful stimuli. Opioid-based therapies are not limited by a ceiling effect; increasing doses will theoretically yield increasing analgesic effects even at extremely high doses. However, increasing doses of opioids are functionally limited by side effects such as nausea, vomiting, constipation, sedation, and respiratory depression.

When used for acute pain, the most common routes of systemic opioid administration include intravenous (IV), intramuscular (IM), and per os (by mouth) (PO). Parenteral routes may also include transdermal (TD), subcutaneous (SC), transmucosal (TM), or iontophoretic/transdermal (ITD). Epidural and intrathecal administration is also used in a variety of settings.

Intravenous administration of opioids ensures a rapid, predictable onset and distribution of analgesic functioning, making this the favored route for the initial treatment of severe acute pain. Intramuscular and enteral routes may result in delayed onset of effects, limiting their effectiveness in the acute pain setting. Similarly, TD (ITD excepted) and SC routes of administration have considerably delayed onset and are more often appropriate for long-term use such as in chronic pain or palliative care settings.

Table 96-1 lists several opioids commonly prescribed for acute and chronic pain medicine. Commonly, patients will experience excellent pain relief following opioids administration. However, there can be a variable response to different formulations and pharmacologic compounds resulting from genetic polymorphisms involving mu-opioid receptor activation, receptor distribution, opioid metabolism, and the type of pain. Opioids are often best at treating static, nociceptive pain such as postsurgical pain, however they are less effective for dynamic or movement-related pain or neuropathic pain. Further, opioids are often ineffective in the treatment of bone fracture pain such as the pain experienced by the patient in the case study.

Opioid conversion: In the course of transitioning from severe acute pain to moderate, subacute pain, physicians will frequently transition the patient from parenteral to oral opioid administration.

1. Calculate the patient's 24-hour opioid use.

2. Convert this to “parenteral morphine equivalent” (PME).

3. The total oral dose prescribed to the patient is commonly less than 100% of the parenteral dose equivalent; this decision is guided by the clinical milieu of the patient including “the patient's recovery from his or her pain.”

4. Consider the division of this requirement into short- and/or long-acting opioids. This decision depends greatly upon the patient, the timing of his or her pain, and the nature of his or her pain.

5. Fifty percent of the 24-hour PME can be given as a sustained preparation, and 50% as shorter-acting, immediate-release medications ordered as needed.

6. To assist the physician with opioid conversion, numerous conversion tables and calculators are available (see www.hopweb.org).

Nonsteroidal Anti-Inflammatory Agents (NSAIDs)

NSAIDs exert their analgesic effect via inhibition of the cyclooxygenase (COX) enzyme, thus interfering with prostaglandin (PG) production. Prostaglandins modify nociceptive thresholds at both peripheral and central sites. By limiting production of PG from COX-1 and COX-2, NSAIDs offer effective analgesia for mild to moderate pain. Further, this mechanism of action apart from the mu-opioid receptor provides a strong supplement to opioids during treatment of moderate to severe pain. Although opioid sparing, NSAIDs do have a ceiling effect, beyond which increasing doses will yield no increase in analgesia. Clinically, NSAIDs decrease pain associated with orthopedic injuries, and those with extensive prostaglandin involvement such as pain from uterine contraction and muscle inflammation. However, the risk of bleeding and mixed evidence regarding interference with union of fractures and spinal surgery necessitates involvement of the operative team in the decision to add NSAIDs.

Traditionally, NSAIDs were nonspecific for the isoforms of cyclooxygenase, COX-1 and COX-2. COX-1 is constitutively expressed in nearly all human tissues, while COX-2 is focally expressed with inflammation. Blockade of COX-1 may promote development of gastrointestinal irritation and bleeding. NSAIDs as a class may also interfere with autoregulation of renal perfusion. To minimize the effects of gastrointestinal irritation and bleeding, drug development turned to selective COX-2 inhibitors. Although effective in minimizing gastrointestinal bleeding, selective COX-2 inhibitors may result in a prothrombotic milieu that may increase the risk of myocardial infarction.

Acetaminophen may represent a special class of NSAIDs. While its mechanism of action is not completely understood, there is evidence of antagonistic activity against COX-2, and a splice variant of COX-1 named COX-3. Notably, acetaminophen appears to not inhibit peripheral COX-1, which may explain its favorable safety profile in regards to gastrointestinal, hematological, cardiovascular, and renal effects seen with other NSAIDs and selective COX-2 inhibitors.

In assessing comparative efficacy, the number of patients needed to treat (NNT) for at least a 50% reduction in pain after 4–6 hours for 1 g of acetaminophen is 4.4, which compares favorably to 650 mg of aspirin or 100 mg of ibuprofen. A more typical dose of ibuprofen, 400 mg, however, had an NNT of only 2.3. Celecoxib, a selective COX-2 inhibitor, has a NNT of 4.5 at 200 mg when compared with placebo for postoperative pain.

Ca-Channel Antagonists (Anticonvulsants) and Tricyclic Antidepressants

Anticonvulsants such as gabapentin and pregabalin have found an increasing role in the treatment of chronic pain stemming from neuropathy. While designed to mimic the structure of gamma-aminobutyric acid (GABA), gabapentin does not actually bind to GABA receptors. Instead, its antihyperalgesic/antiallodynic effect likely stems from binding to the of alpha2delta1 accessory unit of voltage-dependent Ca2 channels within the dorsal root ganglia of the spinal cord, which are upregulated following peripheral nerve injury. By inhibiting these calcium channels, gabapentin and pregabalin my inhibit glutamate release from primary afferent nerve fibers, which activate pain responsive neurons within the spinal cord. Although gabapentin and pregabalin are effective for a myriad of chronic pain conditions, their role in acute pain management is less clear. The gabapentinoids have a clear role in the treatment of postoperative pain when given in the perioperative period (pre- and postoperatively) in a number of major orthopedic and gastrointestinal surgeries. In the acute and chronic pain setting, they have been shown to be opioid sparing and show promise as successful adjuvant analgesics.

Although developed initially for the treatment of depression, low-dose tricyclic antidepressants (TCA) are a mainstay of treatment for many chronic pain states, especially those involving neuropathic pain. Even though their mechanism of action remains unclear, TCAs may augment descending serotonergic and noradrenergic bulbospinal pathways on the dorsal horn of the spinal cord. This class of drugs has significant anticholinergic side effects, so in this case study (elderly and history of dementia), it would be contraindicated to use TCAs. They are titrated to goal dosing to gain benefit while decreasing the side effect profile. One advantageous side effect is somnolence, which is utilized by evening dosing and can facilitate sleep and decrease pain.

Patient-Controlled Analgesia

When compared to intermittent bolus dosing of opioids, IV patient-controlled analgesia (PCA) offers significantly greater analgesia and satisfaction. Both the strengths and risks of PCA systems depend upon a negative feedback loop: when in pain, the patient self-administers potent analgesics leading to pain relief, therefore limiting further opioid demands. An additional benefit of PCA dosing is that the patient is not dependent upon administration variables and has constant access to the prescribed dosing.

PCA systems allow for a continuous and demand dosing. Demand dosing is a preset amount that can be accessed at regulated intervals. This dosing also has an hourly maximum dose with lockout to prevent overmedication. Table 96-2 lists common IV PCA programs for initial use with a variety of opioids.

As with any opioid-based therapy, PCA use may result in respiratory depression. If there is discordance between nociception (pain) and antinociception (opioid), a relative decrease in pain input or increase in opioid-based inhibition may each result in respiratory depression in the presence of opioids. However, minimizing the use of background infusions in opioid-naïve patients mitigates this risk. The incidence of respiratory depression is then decreased below the rate associated with provider-administered intermittent boluses. Background infusions are best used on an individual basis, but can be a method to incorporate a home opioid regimen to better control the overall pain state. Home opioid dosing can be converted to background infusion dosing with the addition of patient controlled dosing to assess and treat in the acute pain phase. Once on a stable regimen that adequately controls the patient's pain, this dosing requirement information can be used to transition to an oral regimen that will reflect the patient's requirements. Some institutions use pulse oximetry monitoring to assess the respiratory depression associated with opioid administration. Unfortunately, this monitoring is not appropriately sensitive, nor is it in any way specific enough to capture the relationship between respiratory depression and opioid administration when it is used concomitantly with supplemental oxygen. Pulse oximetry then lends a false sense of security in addition to monitoring and administrative burden without the benefit of providing predictive value. Capnography is a much more specific correlate of respiratory depression. However, capnography is not readily available in all institutions, nor is it appropriate to apply this universally to patients receiving opioid therapy. Its use would be best reserved for those patients who have substantial comorbidities that elevate the risks associated with opioid therapy.

Interventional Techniques

Peripheral Nerve Blocks

The use of peripheral nerve blocks, either as single injections or continuous infusions of local anesthetic, allows analgesia and anesthesia to be focused toward the locus of pain. Peripheral nerve blocks may offer superior analgesia, decreased opioid consumption, improved pharmacokinetic titration, and increased patient satisfaction when compared with systemic analgesic techniques or placebo.

Anesthetizing a targeted peripheral nerve or nerve plexus using anatomic landmarks, ultrasound, or nerve stimulation performs peripheral nerve blocks. Although single injections of local anesthetic can provide anesthesia and analgesia lasting up to 24 hours, placement of a perineural catheter through the needle allows the therapy to be extended for up to several weeks. Anesthesiologists can customize the regional anesthetic regimen to reflect each patient's surgical, perioperative, and rehabilitation requirements. Multiple injections and/or catheters may be needed to adequately anesthetize pertinent nerve distributions.

Neuraxial Anesthesia

Neuraxial anesthesia refers to injections of local anesthetic and/or opioids into the epidural or intrathecal space, either through a needle as a single-injection or through an indwelling catheter.

Epidural anesthesia: Epidural anesthesia commonly refers to infusion of solutions containing local anesthetic and opioids through a catheter within the epidural space. As the solution infiltrates this potential space, it spreads superiorly and inferiorly within the spinal canal. This spread gives coverage along dermatomal distribution congruent with the level of the catheter or injectate. This spread is slightly affected by gravity and patient positioning; thus, patients may notice epidural effects predominating upon dependent locations when laterally positioned.

Epidural solutions commonly contain mixtures of local anesthetic and opioids. High local anesthetic concentrations will result in sympathectomy, sensory loss, and motor block depending upon the required dose for analgesia. In general, the low concentrations of local anesthetic used for analgesia offer a discriminatory block providing excellent analgesia, minimal sensory inhibition and nearly absent motor block. Opioid-only solutions avoid some side effects such as sympathectomy and motor block, but at the cost of nausea, pruritus, and less-potent analgesia. Solutions combining local anesthetic with opioids provide superior dynamic pain relief, decreased sensory block regression, and decreased local anesthetic dose requirement.

Epidural solutions are commonly delivered through continuous infusions rather than single shot administration. While effective, such infusions fail to account for the dynamic nature of painful conditions. The administration of epidural analgesia using patient-controlled epidural analgesia (PCEA) systems has become more common. The PCEA system allows the patient to self-administer an epidural bolus at a dose and schedule ordered by the physician, while providing continuous background infusion. Such systems allow for patient-controlled individualization of analgesic regimens. When compared with continual infusion-only regimens, PCEA systems offer lower drug use yet greater patient satisfaction.

Epidural side effects: As with all types of medications, epidural analgesia is not without side effects. Local anesthetics can result in anesthesia, motor blockade, and hypotension from sympathectomy. When placed in the lumbar and sacral epidural space, local anesthetics or opioids may result in urinary retention necessitating either bladder catheterization or frequent bladder scans. The lower extremity weakness, and potential orthostatic hypotension associated with epidural analgesia, make appropriate fall precautions necessary.

Sympathectomies due to epidural analgesia can result in profound hypotension, although the incidence with postoperative epidural analgesia averages 0.7–3.0%. If the epidural is dosed to the upper thoracic dermatomes, blockade of the cardiac accelerator fibers may also lead to severe bradycardia. Frequent hemodynamic monitoring is therefore essential during initiation and modification of epidural analgesia involving local anesthetics.

Epidural opioid administration is generally devoid of the hemodynamic perturbations seen with epidural local anesthetics. Side effects are usually those also seen with systemic administration, such as nausea, vomiting, pruritus, and respiratory depression. Pruritus due to neuraxial opioids appears to be related to central activation of “pruritus pathways” that mediate nonhistamine itch. Intravenous naloxone, naltrexone, and nalbuphine each appear efficacious for treatment of opioid-induced pruritus without affecting analgesia when dosed appropriately.

The rate of respiratory depression from neuraxial opioids does not appear to differ from that of systemic opioid administration, ranging from 0.1%–0.9%. The concern for respiratory depression stems from the cephalic spread and systemic distribution of neuraxial opioids. Respiratory depression appears early after bolus with lipophilic opioids such as fentanyl or sufentanil, and may be delayed up to 12 hours with hydrophilic opioids such as morphine. Risk factors include increasing dose, age, concomitant systemic opioid or sedative use, thoracic surgery, prolonged or extensive surgery, and the presence of applicable comorbidities.

Paravertebral anesthesia: Occasionally, situations arise in which a patient would benefit from epidural analgesia confined to a single side of the body, or in which an avoidance of large-segment sympatholysis becomes critical. This can be accomplished by delivering local anesthetics to the paravertebral compartment either through a single injection or via continual infusion via catheter. Such techniques are finding increasing use for unilateral thoracic, breast, abdominal, and hip surgery, and for pain from rib fractures.

Risks of Regional Anesthesia

As with all medical and surgical therapies, the risk-to-benefit ratios of regional anesthesia should be thoroughly discussed with patients prior to implementation. Because regional anesthesia requires apposition of sharp instruments very near the spinal cord or peripheral nerves, there is a rare but catastrophic risk of direct mechanical injury to these structures. Bleeding and infection are likewise possible with any regional anesthetic, especially those related to the central nervous system. With regard to neuraxial and paravertebral analgesia, development of an epidural hematoma may result in spinal cord hypoperfusion, injury, and subsequent permanent paralysis. Epidural hematoma formation may occur during needle or catheter placement, and during catheter removal. Concurrent use of neuraxial or paravertebral analgesia with systemic anticoagulation requires exceptional vigilance to prevent or minimize complications involving epidural hematomas.

Infection represents another major concern, especially with neuraxial analgesia. Serious infections resulting in epidural abscess or meningitis following epidural analgesia are thankfully quite rare (< 1/1000 and < 1/50,000, respectively), although catheter colonization rates may approach 35%.

Medical Comorbidities

Elderly/Dementia/Delirium

Treatment goals:

• Maximizing functionality and pain control while minimizing cognitive side effects.

Treatment modalities:

• Oral medications, topical medications, and interventional therapies.

Special Considerations:

• Elderly patients have both multiple comorbidities and altered liver and kidney physiology, which impact their drug metabolism and clearance. Hepatic drug clearance can be reduced by 30% and renal clearance is decreased by 50% in two-thirds of elderly patients. This makes elderly patients particularly sensitive to many of the pain medications with subsequent CNS effects. Opioids, with the exception of buprenorphine, have increased active half-lives and metabolites. This requires decreased dosing and longer dosing intervals to minimize adverse events. Long-acting opioids can be beneficial due to improved compliance with dosing regimens, particularly transdermal fentanyl. Transdermal fentanyl is best used for patients with chronic pain, not acute or postoperative pain due to the risk of respiratory depression. Cognitive impairment is still a recognized sequelae and titration should be slow and gradual.
• Beers criteria for institutionalized elderly patients include 3-tiered recommendations for medications to avoid. Medications considered inappropriate include flurazepam, pentazocine, and meperidine. Risky medications include long-acting benzodiazepines such as diazepam. A more effective or better alternative medication includes ketorolac. Gurwitz and colleagues evaluated medication use in Medicare beneficiaries and found that 20.1% were on opioids and 19.8% were on nonopioid analgesics in outpatient settings, which resulted in a preventable adverse effect rate of 6.7% and 15.4% respectively.

Obstructive Sleep Apnea

Treatment goals:

• Optimize pain control while minimizing detrimental effects of treatment on respiratory mechanics.

Treatment modalities:

• Avoid opioid and centrally acting agents that suppress respiratory drive as much as possible. These can include adjuvants, NSAIDs, tramadol, regional anesthetics, and the use of home CPAP.

Special considerations:

• One of the most important factors in management is recognition of the disease to employ risk minimization strategies. This has been best evaluated with regard to the perioperative period. Proposed mechanisms for airway obstruction during sedation and anesthesia include factors that impact closing pressure and airway muscle activity leaving these patients more vulnerable to the effects of sedation. Sedatives, anesthetics, and analgesics appear to selectively compromise patients with obstructive sleep apnea (OSA) compared to unaffected individuals. Efficacy of CPAP has not been evaluated in the perioperative period or with concomitant use of analgesics or opioids. Treatment strategies can include minimization of centrally acting respiratory depressants such as opioids and reliance upon nonopioid therapies.

Peripheral Vascular Disease

Treatment goals:

• Peripheral arterial disease is present in 12%–20% of Americans over age 65 with the majority of these patients having asymptomatic disease. Critical limb ischemia is defined as greater than two weeks of rest pain, ulcers, or tissue loss attributed to arterial occlusive disease. The primary mainstay of treatment is evaluation and possible interventional treatment by vascular surgery. Primary treatment modalities include medical therapy, revascularization, or amputation. Increasing numbers of patients are able to undergo revascularization because of developing endovascular strategies. Patients with disease and comorbidities that are not amenable to operable repair are left with medical analgesic therapy or spinal cord stimulation. Spinal cord stimulators are used extensively in Europe for this indication.

Treatment modalities:

• Oral medications, topical medications, and interventional therapies (spinal cord stimulation)

Special considerations:

• Spinal cord stimulator treatment has been found to improve 12-month limb salvage and lower analgesic use in nonoperable patients compared with conservative therapy. Conservative medication therapy can control pain in these patients, but spinal cord stimulation may provide analgesic benefit and facilitate wound healing.

Hepatic Disease/Failure

Treatment goals:

• Hepatic disease can be associated with dysfunction in several pathways that impede pain control strategies. Coagulation issues can preclude interventional management techniques including regional anesthesia, nerve blocks, and other injections. Liver dysfunction can affect opioid metabolism and preclude the use of medications containing acetaminophen.

Treatment modalities:

• Oral and transdermal therapy including opioids that do not have significant disruption of metabolism and additional adjuvants that are comorbidity appropriate.

Special considerations:

• Opioid metabolism can be affected significantly by hepatic insufficiency. Drugs with decreased clearance include meperidine, dextropropoxyphene, pentazocine, tramadol, and alfentanil. Morphine also has decreased clearance and increased oral bioavailability. These drugs can be used but would require a decreased dose or increased dosing interval. Meperidine can be metabolized to normeperidine, an active metabolite that can cause seizures. Fentanyl, sufentanil, and remifentanil metabolism do not appear to be altered.

Renal Disease/Failure

Treatment goals:

• Optimize pain control while minimizing impact upon renal function and adjust medications that are affected by impaired renal function.

Treatment modalities:

• Oral and transdermal analgesics, topical NSAIDs (minimizing systemic absorption), interventional therapies (pain-state specific).

Special considerations:

• Dialysis patients have significant pain that can be undertreated. Barakzoy and colleagues developed a modified WHO ladder paradigm to treat nociceptive and neuropathic pain in end-stage renal disease (ESRD) patients. These modifications include acetaminophen and adjuvants for mild pain; tramadol, hydrocodone, oxycodone, nonopioid analgesics, and adjuvants. Severe pain responded to the addition of hydromorphone, fentanyl, and methadone in addition to the lower-tier recommendations. Patients tolerated these medications well with the most challenging population being elderly patients on dialysis, although pharmacokinetics and side effect profiles are an issue in healthier patients in this age group.
• The use of NSAIDs is associated with an increased rate and severity of side effects in patients with renal dysfunction. These effects can range from electrolyte abnormalities to chronic renal failure on a dose and exposure basis. This relationship is best correlated with the plasma concentration of the NSAIDs, which does not eliminate their usage entirely, but requires caution. Diclofenac is a topical nonsteroidal that has demonstrated benefit in the patch and gel format for osteoarthritis, but has only 2% renal clearance, decreasing that concern in patients with renal insufficiency/failure.

Specific Pain Conditions

Postoperative: Peripheral (Orthopedic)

Treatment goals:

• Improved pain control to improve functionality and work with physical therapy.

Treatment modalities (as per detailed explanation above):

• Catheters and neuraxial blocks, adjunctive agents: neuropathic medications, NSAIDs, opioids: transitioning to oral medications from the PCA.

Special considerations:

• Hip and knee arthroplasty patients are stratified into highest-risk categories for thromboembolic events. Anticoagulation in these patients may direct therapeutic strategies for pain control and require special considerations when working with catheters and neuraxial blocks. NSAIDs use in postspine fusion has mixed evidence and will be dependent upon the individual surgeon's management preferences.

Postoperative: Abdominal/Thoracic

Treatment goals:

• Pain control to improve respiratory status.

Treatment modalities:

• Regional anesthesia has excellent benefits for the postoperative patient. Thoracic epidural for improved pain control without additional respiratory depression. While IV PCA is safe, epidural analgesia allows for superior pain control with an improved side effect profile. Patient satisfaction and surgical outcomes are also improved with the use of epidurals for the first 72 hours postoperatively; however, pruritus can be an issue.
• NPO status can be a directing factor in the pain regimen with these patients. Transitioning these patients from an epidural or IV PCA can be challenging due to limitations in oral dosing because of concerns about absorption issues and opioid-induced bowel dysfunction. Transdermal fentanyl can be a viable option, but is not a first-line choice in postoperative patients without a history of chronic pain because of the risk of respiratory depression.

Chest tube pain/thoracotomy:

• Best managed by thoracic epidural, but once the epidural is removed, lidocaine patch can be a useful option.

Special considerations:

• Opioids have the undesirable side effects of respiratory depression and action on the gastrointestinal system as detailed later.

Ophthalmic Pain

Treatment goals:

• Determining when to consult ophthalmology versus conservative management. Eye pain can be grossly divided into three categories:

  1. Ocular and orbital disorders with or without visible pathology of the eye (eg, redness, corneal opacity, or proptosis)

  2. Ophthalmologic syndromes associated with headache

  3. Headache syndromes associated with ophthalmologic findings.

Treatment modalities:

• Conservative management primarily consists of observation with no active intervention necessary.

Special Considerations:

• Red flags for ophthalmic pain necessitating consultation include:
  Table Graphic Jump Location

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  New visual acuity defect Relative afferent pupillary defect Extraocular muscle abnormality Conjunctival chemosis, injection, or redness Iris irregularity or nonreactive pupil Recent intraocular surgery (within three months) Fundus abnormality (eg, retinal hemorrhages, optic disc edema, or optic atrophy) Iris irregularity or nonreactive pupil

  Color vision defect Visual field loss Ocular misalignment Diplopia Proptosis Corneal opacity Hyphema or hypopyon Recent ocular trauma Lid retraction or ptosis

Stroke Pain: Central Stroke Pain

Treatment goals:

• Central stroke pain is disabling sequelae of stroke in 8%–14% of patients.

Treatment modalities:

• First-line drugs include tricyclic antidepressants and neuropathic agents including pregabalin and gabapentin. Second-line drugs would include selective serotonin–norepinephrine reuptake inhibitors, lamotrigine, opioids, and drug combinations.

Special considerations:

• Diagnosis is made by exclusion of other likely causes of pain in the presence of a history consistent with stroke and pain in a distinct neuroanatomically plausible distribution supported by clinical neurologic examination. This diagnosis is strengthened by indication of a concordant vascular lesion using imaging study.

Neuropathic Pain

Treatment goals:

• Diagnosis of the cause of the neuropathy (ie diabetes mellitus, HIV, chemotherapy-induced peripheral neuropathy) should guide the management to prevent worsening of the neuropathy.

Treatment modalities:

• Oral and transdermal therapies are the primary modalities; spinal cord stimulation can be beneficial for some patients that are refractory to these therapies. First-line medications include tricyclic antidepressants, selective serotonergic and noradrenergic reuptake inhibitors, calcium channel alpha 2-delta ligands (pregabalin and gabapentin), and topical lidocaine. Opioid analgesics and tramadol are considered second-line agents that can be used as first-line treatments in certain patients. Third-line agents include other anticonvulsants, antidepressants, mexiletine, N-Methyl-d-aspartate (NMDA) receptors, and topical capsaicin (Table 96-3).
  Table Graphic Jump Location

  Table 96-3 Neuropathic Pain Medication Guidelines

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  Table 96-3 Neuropathic Pain Medication Guidelines

  Drug	Start Dose	Maximum Dose	Documented Effect	Side Effects
  Gabapentin	300 mg/day	3600 mg/day	PHN, PDN, mixed neuropathic pain	Sedation, dizziness, edema
  Pregabalin	25 mg/day	600 mg/day	PHN, PDN, mixed neuropathic pain, central pain	Sedation, dizziness edema
  Tricyclic antidepressants	25 mg/day (NB: plasma level)	75–150 mg/day (NB: plasma level)	PHN, PDN, central pain, mixed neuropathic pain	Cardiac, anticholinergic, sedation
  Specific serotonergic and noradrenergic reuptake inhibitors			Painful neuropathy	Sedation
  Venlafaxine	37.5 mg/day	25–375 mg/day
  Duloxetine	600 mg/day
  Carbamazepine (oxcarbazepine)	300 mg/day (NB: plasma level)	1200–1800 mg (1/3 higher dose for oxcarbazepine) (NB: plasma level)	Trigeminal neuralgia	Sedation, dizziness, ataxia
  Tramadol	50 mg/day	400 mg/day	Painful neuropathies	Sedation, dizziness, obstipation
  Lamotrigine	25 mg/day* (NB: plasma level)	400–600 mg/day (NB: plasma level)	Trigeminal neuralgia, poststroke central pain	Sedation, tremor, rash
  Opioids	5–10 mg/day, titrate substitute with long-acting opioids	Variable	PHN, PDN, postamputation pain	Sedation, dizziness, tolerance, drug abuse
  Lidocaine patch			PHN, traumatic nerve injury	Allergic reaction
  Capsaicin cream	4x/day for 8wks		PHN, PDN, HIV

  PDN, peripheral diabetic neuropathy; PHN, postherpetic neuralgia.

  *To be titrated slowly.

  Reproduced, with permission, from Jensen, TS et al. Pharmacology and treatment of neuropathic pains. Current Opinion in Neurology. 2009;22:467–474.

Special considerations:

• Herpes zoster vaccination should be considered in appropriate patient populations as one of the only preventative measures for neuropathic pain. Interventional therapies can include spinal cord stimulation.

Phantom Limb Pain

Treatment goals:

• Phantom limb pain occurs in 50%–80% of both traumatic and operative amputees. The prevailing theory is based on central changes with some peripheral and psychological components involved in the development. Cortical reorganization seems to be the primary mechanism with peripheral sensitization, but the developmental mechanism is still unknown. Pain and sensory alterations at the site of amputation predominate in the initial postoperative and posttraumatic period. Phantom limb sensations and pain generally develop within one month of the amputation with a second peak of development approximately 12 months postamputation. Preoperative analgesia has been evaluated as a possibility to improve outcomes, but neither regional anesthetic techniques nor oral regimens have been found to decrease incidence of the development of phantom limb pain.

Treatment modalities:

• Treatment of phantom limb pain may require a multimodal therapeutic regimen. First-line therapies include Transcutaneous electrical nerve stimulation and biofeedback. Medication options include anticonvulsants (gabapentin), opioids, and NSAIDs. Other treatment modalities that have not been investigated fully but have benefitted some patients include: acupuncture, mirror-box therapy, NMDA, and calcitonin receptor agonists.

Special considerations:

• Psychological components, including coping mechanisms, appear to be a component in the development of phantom limb pain. Patients should be evaluated for the need to adjust prosthesis, stump neuroma, referred pain, and care of the residual limb.

Chronic Abdominal Pain/Distention

Treatment goals:

• Minimizing opioids and maintaining motility. Evaluating patients for a correctable pathology is the primary step. This may involve evaluation by the gastroenterology or gynecology service.

Treatment modalities:

• NSAIDs, adjuvant medications, treatment of primary pathology, and interventional strategies.

Special Considerations:

• Opioid-induced constipation is a common side effect that limits the efficacy of this drug class for patients with abdominal pathology. Opioid use also can promote the development of narcotic bowel syndrome (NBS), which is the aggravation of chronic abdominal pain by opioid usage. Exposing patients to opioids for nonmalignant pain puts them at higher risk for developing aberrant drug-related behaviors and illicit drug use. Narcotic bowel syndrome can actually be the etiology of an acute abdominal pain exacerbation, as a diagnosis of exclusion with evaluation that is negative for pathology, moderate opioid usage greater than two weeks, and clinical history. Treatment of this NBS involves several factors including recognition of the syndrome, developing a relationship with the patient to facilitate this process, graded withdrawal of the narcotic according to a specified withdrawal program, and the institution of medications to reduce withdrawal effects.
• Methylnaltrexone is a newer agent that can be used to counteract opioid-induced constipation with minimal central effects and lack of withdrawal potential. These patients should be screened for ileus or other obstructive causes of constipation prior to administration.
• Epidural analgesia can be used for treatment and management of chronic abdominal pain of multifactorial origin. The management is similar to that of postoperative abdominal pain as above.
• Chronic pancreatitis may develop as part of an increased neural density and hypertrophy resulting in a neuropathic pain state, similar to the state that develops in pancreatic adenocarcinoma. Chronic pancreatitis treatment can use the neuropathic pain treatment paradigm as above. The limitation of this therapy is that the NMDA antagonists and tricyclic antidepressants can result in decreased gastrointestinal motility. Lifestyle modifications and analgesics are the mainstay of outpatient treatment. The addition of pancrease can be started under the guidance of gastroenterology and patients may have a reduction in pain associated with this. Tramadol can also be a useful alternative to stronger opioids with regard to pain control and GI motility side effects.
• Oral medications are the mainstay of treatment for this, but some providers will perform celiac plexus blocks/neurolysis. However, these are not permanent procedures with nerve regrowth within three to six months. This is not an entirely benign procedure with complication risks including paralysis. Spinal cord stimulation may prove to be a treatment strategy for refractory severe abdominal visceral pain.

Cancer Pain

Treatment goals:

• Maximizing function and quality of life.

Treatment modalities:

• Oral medication including NSAIDs, opioids, and neuropathic agents, nerve blocks and neurolysis, spinal cord stimulators, and intrathecal therapy.

Special considerations:

• Cancer pain is globally undertreated, with significant impact on quality of life. The World Health Organization developed its “ladder” for treatment of malignant pain (Table 96-4). A major barrier to this is usage, but when implemented, significant proportions receive pain relief.
• Elderly patients dealing with malignant pain are particularly vulnerable to subtherapeutic treatment. In patients with comorbidities, interventional therapies can prove beneficial. These can include somatic/sympathetic blockades, intrathecal therapy, and spinal cord stimulation. Sympathetic blockade/neurolysis can be beneficial for certain pain states; one of the most commonly utilized is the celiac plexus block/neurolysis for pancreatic cancer. This procedure is primarily used for malignant pain due to associated risks, but a large component of efficacy is dependent on the location of the tumor. Neuraxial medication administration (epidural/intrathecal) has been found to be beneficial for both pain control and minimization of side effects. This is usually reserved for pain that is refractory to the WHO paradigm or limited by the side effect profile. This conservative practice of waiting until the cancer pain patient fails other therapies may extend the patients discomfort unnecessarily.

The evaluation and treatment of pain begins with an unbiased assessment of the patient's symptoms, individualized treatment plans that reflect the patient's comorbidities and types of pain, and a reassessment of treatment changes at appropriate intervals so that patients do not suffer needlessly. Hospitalists can improve patient care as they address pain issues across specialties on comanagement and medical services by frequently assessing and effectively communicating with patients as well as being readily available as problems arise. Appropriately converting different opioids and addressing pain issues will not only promote patient safety but patient satisfaction as well.