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InternalMed_Harrison. CHAPTER 18 Pain: Pathophysiology and Management Anticholinergic Orthostatic Cardiac Ave. Dose, Generic Name 5-HT NE Sedative Potency Potency Hypotension Arrhythmia mg/d Range, mg/d Oxcarbazepine 300 bid Pregabalin 150–600 aAntidepressants, anticonvulsants, and antiarrhythmics have not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of pain. 1800 mg/d is FDA approved for postherpetic neuralgia. Abbreviations: 5-HT, serotonin; NE, norepinephrine. acute hypovolemia, should be monitored closely. NSAIDs can also increase blood pressure in some individuals. Long-term treatment with NSAIDs requires regular blood pressure monitoring and treatment if necessary. Although toxic to the liver when taken in high doses, acetaminophen rarely produces gastric irritation and does not interfere with platelet function.


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InternalMed_Harrison. The introduction of parenteral forms of NSAIDs, ketorolac and diclofenac, extends the usefulness of this class of compounds in the management of acute severe pain. Both agents are sufficiently potent and rapid in onset to supplant opioids for many patients with acute severe headache and musculoskeletal pain. bGabapentin in doses up to


InternalMed_Harrison

InternalMed_Harrison. There are two major classes of COX: COX-1 is constitutively expressed, and COX-2 is induced in the inflammatory state. COX-2– selective drugs have similar analgesic potency and produce less gastric irritation than the nonselective COX inhibitors. The use of COX-2–selective drugs does not appear to lower the risk of nephrotoxicity compared to nonselective NSAIDs. On the other hand, COX-2–selective drugs offer a significant benefit in the management of acute postoperative pain because they do not affect blood coagulation. Nonselective COX inhibitors are usually contraindicated postoperatively because they impair platelet-mediated blood clotting and are thus associated with increased bleeding at the operative site. COX-2 inhibitors, including celecoxib (Celebrex), are associated with increased cardiovascular risk. It appears that this is a class effect of NSAIDs, excluding aspirin. These drugs are contraindicated in patients in the immediate period after coronary artery bypass surgery


InternalMed_Harrison

InternalMed_Harrison. cardiovascular risk. It appears that this is a class effect of NSAIDs, excluding aspirin. These drugs are contraindicated in patients in the immediate period after coronary artery bypass surgery and should be used with caution in elderly patients and those with a history of or significant risk factors for cardiovascular disease.


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InternalMed_Harrison. Opioids are the most potent pain-relieving drugs currently available. Of all analgesics, they have the broadest range of efficacy and provide the most reliable and effective method for rapid pain relief. Although side effects are common, most are reversible: nausea, vomiting, pruritus, and constipation are the most frequent and bothersome side effects. Respiratory depression is uncommon at standard analgesic doses, but can be life-threatening. Opioid-related side effects can be reversed rapidly with the narcotic antagonist naloxone. Many physicians, nurses, and patients have a certain trepidation about using opioids that is based on an exaggerated fear of addiction. In fact, there is a vanishingly small chance of patients becoming addicted to narcotics as a result of their appropriate medical use. The physician should not hesitate to use opioid analgesics in patients with acute severe pain. Table 18-1 lists the most commonly used opioid analgesics.


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InternalMed_Harrison. Opioids produce analgesia by actions in the CNS. They activate pain-inhibitory neurons and directly inhibit pain-transmission neurons. Most of the commercially available opioid analgesics act at the same opioid receptor (μ-receptor), differing mainly in potency, speed of onset, duration of action, and optimal route of administration. Some side effects are due to accumulation of nonopioid metabolites that are unique to individual drugs. One striking example of this is normeperidine, a metabolite of meperidine. At higher doses of meperidine, typically greater than 1 g/d, accumulation of normeperidine can produce hyperexcitability and seizures that are not reversible with naloxone. Normeperidine accumulation is increased in patients with renal failure.


InternalMed_Harrison

InternalMed_Harrison. The most rapid pain relief is obtained by intravenous administration of opioids; relief with oral administration is significantly slower. Because of the potential for respiratory depression, patients with any form of respiratory compromise must be kept under close observation following opioid administration; an oxygen-saturation monitor may be useful, but only in a setting where the monitor is under constant surveillance. Opioid-induced respiratory depression is typically accompanied by sedation and a reduction in respiratory rate. A fall in oxygen saturation represents a critical level of respiratory depression and the need for immediate intervention to prevent life-threatening hypoxemia. Ventilatory assistance should be maintained until the opioid-induced respiratory depression has resolved. The opioid antagonist naloxone should be readily available whenever opioids are used at high doses or in patients with compromised pulmonary function. Opioid effects are dose-related, and there


InternalMed_Harrison

InternalMed_Harrison. The opioid antagonist naloxone should be readily available whenever opioids are used at high doses or in patients with compromised pulmonary function. Opioid effects are dose-related, and there is great variability among patients in the doses that relieve pain and produce side effects. Synergistic respiratory depression is common when opioids are administered with other CNS depressants, most commonly the benzodiazepines. Because of this, initiation of therapy requires titration to optimal dose and interval. The most important principle is to provide adequate pain relief. This requires determining whether the drug has adequately relieved the pain and frequent reassessment to determine the optimal interval for dosing. The most common error made by physicians in managing severe pain with opioids is to prescribe an inadequate dose. Because many patients are reluctant to complain, this practice leads to needless suffering. In the absence of sedation at the expected time of peak effect, a


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InternalMed_Harrison. is to prescribe an inadequate dose. Because many patients are reluctant to complain, this practice leads to needless suffering. In the absence of sedation at the expected time of peak effect, a physician should not hesitate to repeat the initial dose to achieve satisfactory pain relief.


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InternalMed_Harrison. An innovative approach to the problem of achieving adequate pain relief is the use of patient-controlled analgesia (PCA). PCA uses a microprocessor-controlled infusion device that can deliver a baseline continuous dose of an opioid drug as well as preprogrammed PART 2 Cardinal Manifestations and Presentation of Diseases additional doses whenever the patient pushes a button. The patient can then titrate the dose to the optimal level. This approach is used most extensively for the management of postoperative pain, but there is no reason why it should not be used for any hospitalized patient with persistent severe pain. PCA is also used for short-term home care of patients with intractable pain, such as that caused by metastatic cancer.


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InternalMed_Harrison. It is important to understand that the PCA device delivers small, repeated doses to maintain pain relief; in patients with severe pain, the pain must first be brought under control with a loading dose before transitioning to the PCA device. The bolus dose of the drug (typically 1 mg of morphine, 0.2 mg of hydromorphone, or 10 μg of fentanyl) can then be delivered repeatedly as needed. To prevent overdosing, PCA devices are programmed with a lockout period after each demand dose is delivered (5–10 min) and a limit on the total dose delivered per hour. Although some have advocated the use of a simultaneous continuous or basal infusion of the PCA drug, this increases the risk of respiratory depression and has not been shown to increase the overall efficacy of the technique.


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InternalMed_Harrison. The availability of new routes of administration has extended the usefulness of opioid analgesics. Most important is the availability of spinal administration. Opioids can be infused through a spinal catheter placed either intrathecally or epidurally. By applying opioids directly to the spinal or epidural space adjacent to the spinal cord, regional analgesia can be obtained using relatively low total doses. Indeed, the dose required to produce effective localized analgesia when using morphine intrathecally (0.1–0.3 mg) is a fraction of that required to produce similar analgesia when administered intravenously (5–10 mg). In this way, side effects such as sedation, nausea, and respiratory depression can be minimized. This approach has been used extensively during labor and delivery and for postoperative pain relief following surgical procedures. Continuous intrathecal delivery via implanted spinal drug-delivery systems is now commonly used, particularly for the treatment of


InternalMed_Harrison

InternalMed_Harrison. and for postoperative pain relief following surgical procedures. Continuous intrathecal delivery via implanted spinal drug-delivery systems is now commonly used, particularly for the treatment of cancer-related pain that would require sedating doses for adequate pain control if given systemically. Opioids can also be given intranasally (butorphanol), rectally, and transdermally (fentanyl and buprenorphine), or through the oral mucosa (fentanyl), thus avoiding the discomfort of frequent injections in patients who cannot be given oral medication. The fentanyl and buprenorphine transdermal patches have the advantage of providing fairly steady plasma levels, which maximizes patient comfort.


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InternalMed_Harrison. Recent additions to the armamentarium for treating opioid-induced side effects are the peripherally acting opioid antagonists alvimopan (Entereg) and methylnaltrexone (Rellistor). Alvimopan is available as an orally administered agent that is restricted to the intestinal lumen by limited absorption; methylnaltrexone is available in a subcutaneously administered form that has virtually no penetration into the CNS. Both agents act by binding to peripheral μ-receptors, thereby inhibiting or reversing the effects of opioids at these peripheral sites. The action of both agents is restricted to receptor sites outside of the CNS; thus, these drugs can reverse the adverse effects of opioid analgesics that are mediated through their peripheral receptors without reversing their analgesic effects. Alvimopan has proven effective in lowering the duration of persistent ileus following abdominal surgery in patients receiving opioid analgesics for postoperative pain control. Methylnaltrexone has


InternalMed_Harrison

InternalMed_Harrison. Alvimopan has proven effective in lowering the duration of persistent ileus following abdominal surgery in patients receiving opioid analgesics for postoperative pain control. Methylnaltrexone has proven effective for relief of opioid-induced constipation in patients taking opioid analgesics on a chronic basis.


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InternalMed_Harrison. Opioid and COX Inhibitor Combinations When used in combination, opioids and COX inhibitors have additive effects. Because a lower dose of each can be used to achieve the same degree of pain relief and their side effects are nonadditive, such combinations are used to lower the severity of dose-related side effects. However, fixed-ratio combinations of an opioid with acetaminophen carry an important risk. Dose escalation as a result of increased severity of pain or decreased opioid effect as a result of tolerance may lead to ingestion of levels of acetaminophen that are toxic to the liver. Although acetaminophen-related hepatotoxicity is uncommon, it remains a significant cause for liver failure. Thus, many practitioners have moved away from the use of opioid-acetaminophen combination analgesics to avoid the risk of excessive acetaminophen exposure as the dose of the analgesic is escalated.


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InternalMed_Harrison. Managing patients with chronic pain is intellectually and emotionally challenging. The patient’s problem is often difficult or impossible to diagnose with certainty; such patients are demanding of the physician’s time and often appear emotionally distraught. The traditional medical approach of seeking an obscure organic pathology is usually unhelpful. On the other hand, psychological evaluation and behaviorally based treatment paradigms are frequently helpful, particularly in the setting of a multidisciplinary pain-management center. Unfortunately, this approach, while effective, remains largely underused in current medical practice.


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InternalMed_Harrison. There are several factors that can cause, perpetuate, or exacerbate chronic pain. First, of course, the patient may simply have a disease that is characteristically painful for which there is presently no cure. Arthritis, cancer, chronic daily headaches, fibromyalgia, and diabetic neuropathy are examples of this. Second, there may be secondary perpetuating factors that are initiated by disease and persist after that disease has resolved. Examples include damaged sensory nerves, sympathetic efferent activity, and painful reflex muscle contraction (spasm). Finally, a variety of psychological conditions can exacerbate or even cause pain.


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InternalMed_Harrison. There are certain areas to which special attention should be paid in a patient’s medical history. Because depression is the most common emotional disturbance in patients with chronic pain, patients should be questioned about their mood, appetite, sleep patterns, and daily activity. A simple standardized questionnaire, such as the Beck Depression Inventory, can be a useful screening device. It is important to remember that major depression is a common, treatable, and potentially fatal illness. Other clues that a significant emotional disturbance is contributing to a patient’s chronic pain complaint include pain that occurs in multiple, unrelated sites; a pattern of recurrent, but separate, pain problems beginning in childhood or adolescence; pain beginning at a time of emotional trauma, such as the loss of a parent or spouse; a history of physical or sexual abuse; and past or present substance abuse.


InternalMed_Harrison

InternalMed_Harrison. On examination, special attention should be paid to whether the patient guards the painful area and whether certain movements or postures are avoided because of pain. Discovering a mechanical component to the pain can be useful both diagnostically and therapeutically. Painful areas should be examined for deep tenderness, noting whether this is localized to muscle, ligamentous structures, or joints. Chronic myofascial pain is very common, and, in these patients, deep palpation may reveal highly localized trigger points that are firm bands or knots in muscle. Relief of the pain following injection of local anesthetic into these trigger points supports the diagnosis. A neuropathic component to the pain is indicated by evidence of nerve damage, such as sensory impairment, exquisitely sensitive skin (allodynia), weakness, and muscle atrophy, or loss of deep tendon reflexes. Evidence suggesting sympathetic nervous system involvement includes the presence of diffuse swelling, changes in skin


InternalMed_Harrison

InternalMed_Harrison. skin (allodynia), weakness, and muscle atrophy, or loss of deep tendon reflexes. Evidence suggesting sympathetic nervous system involvement includes the presence of diffuse swelling, changes in skin color and temperature, and hypersensitive skin and joint tenderness compared with the normal side. Relief of the pain with a sympathetic block supports the diagnosis, but once the condition becomes chronic, the response to sympathetic blockade is of variable magnitude and duration; the role for repeated sympathetic blocks in the overall management of CRPS is not established.


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InternalMed_Harrison. A guiding principle in evaluating patients with chronic pain is to assess both emotional and organic factors before initiating therapy. Addressing these issues together, rather than waiting to address emotional issues after organic causes of pain have been ruled out, improves compliance in part because it assures patients that a psychological evaluation does not mean that the physician is questioning the validity of their complaint. Even when an organic cause for a patient’s pain can be found, it is still wise to look for other factors. For example, a cancer patient with painful bony metastases may have additional pain due to nerve damage and may also be depressed. Optimal therapy requires that each of these factors be looked for and treated.


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InternalMed_Harrison. Once the evaluation process has been completed and the likely causative and exacerbating factors identified, an explicit treatment plan should be developed. An important part of this process is to identify specific and realistic functional goals for therapy, such as getting a good night’s sleep, being able to go shopping, or returning to work. A multidisciplinary approach that uses medications, counseling, physical therapy, nerve blocks, and even surgery may be required to improve the patient’s quality of life. There are also some newer, relatively invasive procedures that can be helpful for some patients with intractable pain. These include image-guided interventions such as epidural injection of glucocorticoids for acute radicular pain and radiofrequency treatment of the facet joints for chronic facet-related back and neck pain. For patients with severe and persistent pain that is unresponsive to more conservative treatment, placement of electrodes within the spinal canal overlying


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InternalMed_Harrison. chronic facet-related back and neck pain. For patients with severe and persistent pain that is unresponsive to more conservative treatment, placement of electrodes within the spinal canal overlying the dorsal columns of the spinal cord (spinal cord stimulation) or implantation of intrathecal drug-delivery systems has shown significant benefit. The criteria for predicting which patients will respond to these procedures continue to evolve. They are generally reserved for patients who have not responded to conventional pharmacologic approaches. Referral to a multidisciplinary pain clinic for a full evaluation should precede any invasive procedure. Such referrals are clearly not necessary for all chronic pain patients. For some, pharmacologic management alone can provide adequate relief.


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InternalMed_Harrison. The tricyclic antidepressants (TCAs), particularly nortriptyline and desipramine (Table 18-1), are useful for the management of chronic pain. Although developed for the treatment of depression, the TCAs have a spectrum of dose-related biologic activities that include analgesia in a variety of chronic clinical conditions. Although the mechanism is unknown, the analgesic effect of TCAs has a more rapid onset and occurs at a lower dose than is typically required for the treatment of depression. Furthermore, patients with chronic pain who are not depressed obtain pain relief with antidepressants. There is evidence that TCAs potentiate opioid analgesia, so they may be useful adjuncts for the treatment of severe persistent pain such as occurs with malignant tumors. Table 18-2 lists some of the painful conditions that respond to TCAs. TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia, for which there are few


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InternalMed_Harrison. painful conditions that respond to TCAs. TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia, for which there are few other therapeutic options.


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InternalMed_Harrison. The TCAs that have been shown to relieve pain have significant side effects (Table 18-1; Chap. 466). Some of these side effects, such as orthostatic hypotension, drowsiness, cardiac conduction delay, memory impairment, constipation, and urinary retention, Rheumatoid arthritisa,b aControlled trials demonstrate analgesia. bControlled studies indicate benefit but not analgesia.


InternalMed_Harrison

InternalMed_Harrison. Rheumatoid arthritisa,b aControlled trials demonstrate analgesia. bControlled studies indicate benefit but not analgesia. CHAPTER 18 Pain: Pathophysiology and Management are particularly problematic in elderly patients, and several are additive to the side effects of opioid analgesics. The selective serotonin reuptake inhibitors such as fluoxetine (Prozac) have fewer and less serious side effects than TCAs, but they are much less effective for relieving pain. It is of interest that venlafaxine (Effexor) and duloxetine (Cymbalta), which are nontricyclic antidepressants that block both serotonin and norepinephrine reuptake, appear to retain most of the pain-relieving effect of TCAs with a side effect profile more like that of the selective serotonin reuptake inhibitors. These drugs may be particularly useful in patients who cannot tolerate the side effects of TCAs.


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InternalMed_Harrison. These drugs are useful primarily for patients with neuropathic pain. Phenytoin (Dilantin) and carbamazepine (Tegretol) were first shown to relieve the pain of trigeminal neuralgia. This pain has a characteristic brief, shooting, electric shock–like quality. In fact, anticonvulsants seem to be particularly helpful for pains that have such a lancinating quality. Newer anticonvulsants, gabapentin (Neurontin) and pregabalin (Lyrica), are effective for a broad range of neuropathic pains. Furthermore, because of their favorable side effect profile, these newer anticonvulsants are often used as first-line agents.


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InternalMed_Harrison. The long-term use of opioids is accepted for patients with pain due to malignant disease. Although opioid use for chronic pain of nonmalignant origin is controversial, it is clear that, for many patients, opioids are the only option that produces meaningful pain relief. This is understandable because opioids are the most potent and have the broadest range of efficacy of any analgesic medications. Although addiction is rare in patients who first use opioids for pain relief, some degree of tolerance and physical dependence is likely with long-term use. Furthermore, animal studies suggest that long-term opioid therapy may worsen pain in some individuals. Therefore, before embarking on opioid therapy, other options should be explored, and the limitations and risks of opioids should be explained to the patient. It is also important to point out that some opioid analgesic medications have mixed agonist-antagonist properties (e.g., butorphanol and buprenorphine). From a practical standpoint,


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InternalMed_Harrison. to the patient. It is also important to point out that some opioid analgesic medications have mixed agonist-antagonist properties (e.g., butorphanol and buprenorphine). From a practical standpoint, this means that they may worsen pain by inducing an abstinence syndrome in patients who are physically dependent on other opioid analgesics.


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InternalMed_Harrison. With long-term outpatient use of orally administered opioids, it is desirable to use long-acting compounds such as levorphanol, methadone, sustained-release morphine, or transdermal fentanyl (Table 18-1). The pharmacokinetic profiles of these drug preparations enable the maintenance of sustained analgesic blood levels, potentially minimizing side effects such as sedation that are associated with high peak plasma levels, and reducing the likelihood of rebound pain associated with a rapid fall in plasma opioid concentration. Although long-acting opioid preparations may provide superior pain relief in patients with a continuous pattern of ongoing pain, others suffer from intermittent severe episodic pain and experience superior pain control and fewer side effects with the periodic use of short-acting opioid analgesics. Constipation is a virtually universal side effect of opioid use and should be treated expectantly. As noted above in the discussion of acute pain treatment, a recent


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InternalMed_Harrison. short-acting opioid analgesics. Constipation is a virtually universal side effect of opioid use and should be treated expectantly. As noted above in the discussion of acute pain treatment, a recent advance for patients is the development of peripherally acting opioid antagonists that can reverse the constipation associated with opioid use without interfering with analgesia.


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InternalMed_Harrison. Soon after the introduction of a controlled-release oxycodone formulation (OxyContin) in the late 1990s, a dramatic rise in emergency department visits and deaths associated with oxycodone ingestion appeared, focusing public attention on misuse of prescription pain medications. The magnitude of prescription opioid abuse has grown over the last decade, leading the Centers for Disease Control and Prevention to classify prescription opioid analgesic abuse as an epidemic. This appears to be due in large part to individuals using a prescription drug nonmedically, most often an opioid analgesic. PART 2 Cardinal Manifestations and Presentation of Diseases guiDELinES foR SELECTing AnD MoniToRing PATiEnTS RECEiving CHRoniC oPioiD THERAPy (CoT) foR THE TREATMEnT of CHRoniC, nonCAnCER PAin • Conduct a history, physical examination, and appropriate testing, including an assessment of risk of substance abuse, misuse, or addiction.


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InternalMed_Harrison. • Consider a trial of COT if pain is moderate or severe, pain is having an adverse impact on function or quality of life, and potential therapeutic benefits outweigh potential harms. • A benefit-to-harm evaluation, including a history, physical examination, and appropriate diagnostic testing, should be performed and documented before and on an ongoing basis during COT. Informed Consent and Use of Management Plans • Informed consent should be obtained. A continuing discussion with the patient regarding COT should include goals, expectations, potential risks, and alternatives to COT. • Consider using a written COT management plan to document patient and clinician responsibilities and expectations and assist in patient education. • Initial treatment with opioids should be considered as a therapeutic trial to determine whether COT is appropriate.


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InternalMed_Harrison. • Initial treatment with opioids should be considered as a therapeutic trial to determine whether COT is appropriate. • Opioid selection, initial dosing, and titration should be individualized according to the patient’s health status, previous exposure to opioids, attainment of therapeutic goals, and predicted or observed harms. patients on COT periodically and as warranted by changing circumstances. Monitoring should include documentation of pain intensity and level of functioning, assessments of progress toward achieving therapeutic goals, presence of adverse events, and adherence to prescribed therapies. patients on COT who are at high risk or who have engaged in aberrant drug-related behaviors, clinicians should periodically obtain urine drug screens or other information to confirm adherence to the COT plan of care.


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InternalMed_Harrison. • In patients on COT not at high risk and not known to have engaged in aberrant drug-related behaviors, clinicians should consider periodically obtaining urine drug screens or other information to confirm adherence to the COT plan of care. Source: Adapted with permission from R Chou et al: J Pain 10:113, 2009.


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InternalMed_Harrison. Source: Adapted with permission from R Chou et al: J Pain 10:113, 2009. Drug-induced deaths have rapidly risen and are now the second leading cause of death in Americans, just behind motor vehicle fatalities. In 2011, the Office of National Drug Control Policy established a multifaceted approach to address prescription drug abuse, including Prescription Drug Monitoring Programs that allow practitioners to determine if patients are receiving prescriptions from multiple providers and use of law enforcement to eliminate improper prescribing practices. This increased scrutiny leaves many practitioners hesitant to prescribe opioid analgesics, other than for brief periods to control pain associated with illness or injury. For now, the choice to begin chronic opioid therapy for a given patient is left to the individual practitioner. Pragmatic guidelines for properly selecting and monitoring patients receiving chronic opioid therapy are shown in Table 18-3.


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InternalMed_Harrison. It is important to individualize treatment for patients with neuropathic pain. Several general principles should guide therapy: the first is to move quickly to provide relief, and the second is to minimize drug side effects. For example, in patients with postherpetic neuralgia and significant cutaneous hypersensitivity, topical lidocaine (Lidoderm patches) can provide immediate relief without side effects. Anticonvulsants (gabapentin or pregabalin; see above) or antidepressants (nortriptyline, desipramine, duloxetine, or venlafaxine) can be used as first-line drugs for patients with neuropathic pain. Systemically administered antiarrhythmic drugs such as lidocaine and mexiletine are less likely to be effective; although intravenous infusion of lidocaine can provide analgesia for patients with different types of neuropathic pain, the relief is usually transient, typically lasting just hours after the cessation of the infusion.


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InternalMed_Harrison. The oral lidocaine congener mexiletine is poorly tolerated, producing frequent gastrointestinal adverse effects. There is no consensus on which class of drug should be used as a first-line treatment for any chronically painful condition. However, because relatively high doses of anticonvulsants are required for pain relief, sedation is very common. Sedation is also a problem with TCAs but is much less of a problem with serotonin/norepinephrine reuptake inhibitors (SNRIs; e.g., venlafaxine and duloxetine). Thus, in the elderly or in patients whose daily activities require high-level mental activity, these drugs should be considered the first line. In contrast, opioid medications should be used as a secondor third-line drug class. Although highly effective for many painful conditions, opioids are sedating, and their effect tends to lessen over time, leading to dose escalation and, occasionally, a worsening of pain due to physical dependence. Drugs of different classes can be used in


InternalMed_Harrison

InternalMed_Harrison. are sedating, and their effect tends to lessen over time, leading to dose escalation and, occasionally, a worsening of pain due to physical dependence. Drugs of different classes can be used in combination to optimize pain control.


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InternalMed_Harrison. It is worth emphasizing that many patients, especially those with chronic pain, seek medical attention primarily because they are suffering and because only physicians can provide the medications required for pain relief. A primary responsibility of all physicians is to minimize the physical and emotional discomfort of their patients. Familiarity with pain mechanisms and analgesic medications is an important step toward accomplishing this aim.


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InternalMed_Harrison. Chest Discomfort David A. Morrow Chest discomfort is among the most common reasons for which patients present for medical attention at either an emergency depart-ment (ED) or an outpatient clinic. The evaluation of nontraumatic chest discomfort is inherently challenging owing to the broad variety 19 of possible causes, a minority of which are life-threatening conditions that should not be missed. It is helpful to frame the initial diagnostic assessment and triage of patients with acute chest discomfort around three categories: (1) myocardial ischemia; (2) other cardiopulmonary causes (pericardial disease, aortic emergencies, and pulmonary conditions); and (3) non-cardiopulmonary causes. Although rapid identification of high-risk conditions is a priority of the initial assessment, strategies that incorporate routine liberal use of testing carry the potential for adverse effects of unnecessary investigations.


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InternalMed_Harrison. Chest discomfort is the third most common reason for visits to the ED in the United States, resulting in 6 to 7 million emergency visits each year. More than 60% of patients with this presentation are hospitalized for further testing, and the rest undergo additional investigation in the ED. Fewer than 25% of evaluated patients are eventually diagnosed with acute coronary syndrome (ACS), with rates of 5–15% in most series of unselected populations. In the remainder, the most common diagnoses are gastrointestinal causes (Fig. 19-1), and fewer than 10% are other life-threatening cardiopulmonary conditions. In a large proportion of patients with transient acute chest discomfort, ACS or another acute cardiopulmonary cause is excluded but the cause is not determined. Therefore, the resources and time devoted to the evaluation of chest discomfort in the absence of a severe cause are substantial. Nevertheless, a disconcerting 2–6% of patients with chest discomfort of presumed non-ischemic


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InternalMed_Harrison. and time devoted to the evaluation of chest discomfort in the absence of a severe cause are substantial. Nevertheless, a disconcerting 2–6% of patients with chest discomfort of presumed non-ischemic etiology who are discharged from the ED are later deemed to have had a missed myocardial infarction (MI). Patients with a missed diagnosis of MI have a 30-day risk of death that is double that of their counterparts who are hospitalized.


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InternalMed_Harrison. The natural histories of ACS, acute pericardial diseases, pulmonary embolism, and aortic emergencies are discussed in Chaps. 288, 294 and 295, 300, and 301, respectively. In a study of more than 350,000 patients with unspecified presumed non-cardiopulmonary chest discomfort, the mortality rate 1 year after discharge was <2% and did not differ significantly from age-adjusted mortality in the general population. The estimated rate of major cardiovascular events through 30 days in patients with acute chest pain who had been stratified as low risk was 2.5% in a large population-based study that excluded patients with ST-segment elevation or definite noncardiac chest pain. The major etiologies of chest discomfort are discussed in this section and summarized in Table 19-1. Additional elements of the history, physical examination, and diagnostic testing that aid in distinguishing these causes are discussed in a later section (see “Approach to the Patient”).


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InternalMed_Harrison. Myocardial ischemia causing chest discomfort, termed angina pectoris, is a primary clinical concern in patients presenting with chest symptoms. Myocardial ischemia is precipitated by an imbalance between myocardial oxygen requirements and myocardial oxygen supply, resulting in insufficient delivery of oxygen to meet the heart’s metabolic demands. Myocardial oxygen consumption may be elevated by increases in heart rate, ventricular wall stress, and myocardial contractility, whereas myocardial oxygen supply is determined by coronary Gastrointestinal 42% Ischemic heart disease 31% Chest wall syndrome 28% Pericarditis 4% Pleuritis 2% Pulmonary embolism 2% Lung cancer 1.5% Aortic aneurysm 1% Aortic stenosis 1% Herpes zoster 1% FIguRE 19-1 Distribution of final discharge diagnoses in patients with nontraumatic acute chest pain. (Figure prepared from data in P Fruergaard et al: Eur Heart J 17:1028, 1996.) PART 2 Cardinal Manifestations and Presentation of Diseases


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InternalMed_Harrison. PART 2 Cardinal Manifestations and Presentation of Diseases Gastrointenstinal Esophageal reflux 10–60 min Burning Substernal, epigastric Worsened by postprandial recumbency; relieved by antacids Esophageal spasm 2–30 min Pressure, tightness, Retrosternal Can closely mimic angina burning Peptic ulcer Prolonged; 60–90 min Burning Epigastric, substernal Relieved with food or antacids after meals Gallbladder disease Prolonged Aching or colicky Epigastric, right upper May follow meal quadrant; sometimes to the back Neuromuscular Costochondritis Variable Aching Sternal Sometimes swollen, tender, warm over joint; may be reproduced by localized pressure on examination Trauma or strain Usually constant Aching Localized to area of Reproduced by movement or strain palpation Herpes zoster Usually prolonged Sharp or burning Dermatomal distribution Vesicular rash in area of discomfort


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InternalMed_Harrison. Herpes zoster Usually prolonged Sharp or burning Dermatomal distribution Vesicular rash in area of discomfort Psychological Emotional and psy-Variable; may be fleeting Variable; often mani-Variable; may be Situational factors may precipitate chiatric conditions or prolonged fests as tightness and retrosternal symptoms; history of panic attacks, dyspnea with feeling of blood flow and coronary arterial oxygen content. When myocardial ischemia is sufficiently severe and prolonged in duration (as little as 20 min), irreversible cellular injury occurs, resulting in MI.


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InternalMed_Harrison. Ischemic heart disease is most commonly caused by atheromatous plaque that obstructs one or more of the epicardial coronary arteries. Stable ischemic heart disease (Chap. 293) usually results from the gradual atherosclerotic narrowing of the coronary arteries. Stable angina is characterized by ischemic episodes that are typically precipitated by a superimposed increase in oxygen demand during physical exertion and relieved upon resting. Ischemic heart disease becomes unstable most commonly when rupture or erosion of one or more atherosclerotic lesions triggers coronary thrombosis (Chap. 291e). Unstable ischemic heart disease is classified clinically by the presence or absence of detectable myocardial injury and the presence or absence of ST-segment elevation on the patient’s electrocardiogram (ECG). When acute coronary atherothrombosis occurs, the intracoronary thrombus may be partially obstructive, generally leading to myocardial ischemia in the absence of ST-segment elevation.


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InternalMed_Harrison. (ECG). When acute coronary atherothrombosis occurs, the intracoronary thrombus may be partially obstructive, generally leading to myocardial ischemia in the absence of ST-segment elevation. Marked by ischemic symptoms at rest, with minimal activity, or in an accelerating pattern, unstable ischemic heart disease is classified as unstable angina when there is no detectable myocardial injury and as non–ST elevation MI (NSTEMI) when there is evidence of myocardial necrosis (Chap. 294). When the coronary thrombus is acutely and completely occlusive, transmural myocardial ischemia usually ensues, with ST-segment elevation on the ECG and myocardial necrosis leading to a diagnosis of ST elevation MI (STEMI, see Chap. 295).


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InternalMed_Harrison. Clinicians should be aware that unstable ischemic symptoms may also occur predominantly because of increased myocardial oxygen demand (e.g., during intense psychological stress or fever) or because of decreased oxygen delivery due to anemia, hypoxia, or hypotension. However, the term acute coronary syndrome, which encompasses unstable angina, NSTEMI, and STEMI, is in general reserved for ischemia precipitated by acute coronary atherothrombosis. In order to guide therapeutic strategies, a standardized system for classification of MI has been expanded to discriminate MI resulting from acute coronary thrombosis (type 1) from MI occurring secondary to other imbalances of myocardial oxygen supply and demand (type 2; see Chap. 294).


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InternalMed_Harrison. Other contributors to stable and unstable ischemic heart disease, such as endothelial dysfunction, microvascular disease, and vasospasm, may exist alone or in combination with coronary atherosclerosis and may be the dominant cause of myocardial ischemia in some patients. Moreover, non-atherosclerotic processes, including congenital abnormalities of the coronary vessels, myocardial bridging, coronary arteritis, and radiation-induced coronary disease, can lead to coronary obstruction. In addition, conditions associated with extreme myocardial oxygen demand and impaired endocardial blood flow, such as aortic valve disease (Chap. 301), hypertrophic cardiomyopathy, or idiopathic dilated cardiomyopathy (Chap. 287), can precipitate myocardial ischemia in patients with or without underlying obstructive atherosclerosis.


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InternalMed_Harrison. Characteristics of Ischemic Chest Discomfort The clinical characteristics of angina pectoris, often referred to simply as “angina,” are highly similar whether the ischemic discomfort is a manifestation of stable ischemic heart disease, unstable angina, or MI; the exceptions are differences in the pattern and duration of symptoms associated with these syndromes (Table 19-1). Heberden initially described angina as a sense of “strangling and anxiety.” Chest discomfort characteristic of myocardial ischemia is typically described as aching, heavy, squeezing, crushing, or constricting. However, in a substantial minority of patients, the quality of discomfort is extremely vague and may be described as a mild tightness, or merely an uncomfortable feeling, that sometimes is experienced as numbness or a burning sensation. The site of the discomfort is usually retrosternal, but radiation is common and generally occurs down the ulnar surface of the left arm; the right arm, both arms, neck, jaw,


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InternalMed_Harrison. or a burning sensation. The site of the discomfort is usually retrosternal, but radiation is common and generally occurs down the ulnar surface of the left arm; the right arm, both arms, neck, jaw, or shoulders may also be involved. These and other characteristics of ischemic chest discomfort pertinent to discrimination from other causes of chest pain are discussed later in this chapter (see “Approach to the Patient”).


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InternalMed_Harrison. Stable angina usually begins gradually and reaches its maximal intensity over a period of minutes before dissipating within several minutes with rest or with nitroglycerin. The discomfort typically occurs predictably at a characteristic level of exertion or psychological stress. By definition, unstable angina is manifest by self-limited anginal chest discomfort that is exertional but occurs at increased frequency with progressively lower intensity of physical activity or even at rest. Chest discomfort associated with MI is typically more severe, is prolonged (usually lasting ≥30 min), and is not relieved by rest.


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InternalMed_Harrison. Mechanisms of Cardiac Pain The neural pathways involved in ischemic cardiac pain are poorly understood. Ischemic episodes are thought to excite local chemosensitive and mechanoreceptive receptors that, in turn, stimulate release of adenosine, bradykinin, and other substances that activate the sensory ends of sympathetic and vagal afferent fibers. The afferent fibers traverse the nerves that connect to the upper five thoracic sympathetic ganglia and upper five distal thoracic roots of the spinal cord. From there, impulses are transmitted to the thalamus. Within the spinal cord, cardiac sympathetic afferent impulses may converge with impulses from somatic thoracic structures, and this convergence may be the basis for referred cardiac pain. In addition, cardiac vagal afferent fibers synapse in the nucleus tractus solitarius of the medulla and then descend to the upper cervical spinothalamic tract, and this route may contribute to anginal pain experienced in the neck and jaw.


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InternalMed_Harrison. OTHER CARDIOPuLMONARY CAuSES Pericardial and Other Myocardial Diseases (See also Chap. 288)


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InternalMed_Harrison. Inflammation of the pericardium due to infectious or noninfectious causes can be responsible for acute or chronic chest discomfort. The visceral surface and most of the parietal surface of the pericardium are insensitive to pain. Therefore, the pain of pericarditis is thought to arise principally from associated pleural inflammation and is more common with infectious causes of pericarditis, which typically involve the pleura. Because of this pleural association, the discomfort of pericarditis is usually pleuritic pain that is exacerbated by breathing, coughing, or changes in position. Moreover, owing to the overlapping sensory supply of the central diaphragm via the phrenic nerve with somatic sensory fibers originating in the third to fifth cervical segments, the pain of pleural pericarditis is often referred to the shoulder and neck. Involvement of the pleural surface of the lateral diaphragm can lead to pain in the upper abdomen.


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InternalMed_Harrison. Acute inflammatory and other non-ischemic myocardial diseases can also produce chest discomfort. The symptoms of Takotsubo (stress-related) cardiomyopathy often start abruptly with chest pain and shortness of breath. This form of cardiomyopathy, in its most recognizable form, is triggered by an emotionally or physically stressful event and may mimic acute MI because of its commonly associated ECG abnormalities, including ST-segment elevation, and elevated biomarkers of myocardial injury. Observational studies support a predilection for women >50 years of age. The symptoms of acute myocarditis are highly varied. Chest discomfort may either originate with inflammatory injury of the myocardium or be due to severe increases in wall stress related to poor ventricular performance.


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InternalMed_Harrison. Diseases of the Aorta (See also Chap. 301) Acute aortic dissection (Fig. 19-1) is a less common cause of chest discomfort but is important because of the catastrophic natural history of certain subsets of cases when recognized late or left untreated. Acute aortic syndromes encompass a spectrum of acute aortic diseases related to disruption of the media of the aortic wall. Aortic dissection involves a tear in the aortic intima, resulting in separation of the media and creation of a separate “false” lumen. A penetrating ulcer has been described as ulceration of an aortic atheromatous plaque that extends through the intima and into the aortic media, with the potential to initiate an intramedial dissection or rupture into the adventitia. Intramural hematoma is an aortic wall hematoma with no demonstrable intimal flap, no radiologically apparent intimal tear, and no false lumen. Intramural hematoma can occur due to either rupture of the vasa vasorum or, less commonly, a penetrating ulcer.


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InternalMed_Harrison. Each of these subtypes of acute aortic syndrome typically presents with chest discomfort that is often severe, sudden in onset, and sometimes described as “tearing” in quality. Acute aortic syndromes involving the ascending aorta tend to cause pain in the midline of the anterior chest, whereas descending aortic syndromes most often present with pain in the back. Therefore, dissections that begin in the ascending aorta and extend to the descending aorta tend to cause pain in the front of the chest that extends toward the back, between the shoulder blades. Proximal aortic dissections that involve the ascending aorta (type A in the Stanford nomenclature) are at high risk for major complications that may influence the clinical presentation, including (1) compromise of the aortic ostia of the coronary arteries, resulting in MI; (2) disruption of the aortic valve, causing acute aortic insufficiency; and (3) rupture of the hematoma into the pericardial space, leading to pericardial


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InternalMed_Harrison. of the coronary arteries, resulting in MI; (2) disruption of the aortic valve, causing acute aortic insufficiency; and (3) rupture of the hematoma into the pericardial space, leading to pericardial tamponade.


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InternalMed_Harrison. Knowledge of the epidemiology of acute aortic syndromes can be helpful in maintaining awareness of this relatively uncommon group of disorders (estimated annual incidence, 3 cases per 100,000 population). Nontraumatic aortic dissections are very rare in the absence of hypertension or conditions associated with deterioration of the elastic or muscular components of the aortic media, including pregnancy, bicuspid aortic disease, or inherited connective tissue diseases, such as Marfan and Ehlers-Danlos syndromes. Although aortic aneurysms are most often asymptomatic, thoracic aortic aneurysms can cause chest pain and other symptoms by compressing adjacent structures. This pain tends to be steady, deep, and occasionally severe. Aortitis, whether of noninfectious or infectious etiology, in the absence of aortic dissection is a rare cause of chest or back discomfort.


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InternalMed_Harrison. Pulmonary Conditions Pulmonary and pulmonary-vascular conditions that cause chest discomfort usually do so in conjunction with dyspnea and often produce symptoms that have a pleuritic nature.


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InternalMed_Harrison. PULMONARY EMBOLISM (See also Chap. 300) Pulmonary emboli (annual incidence, ~1 per 1000) can produce dyspnea and chest discomfort that is sudden in onset. Typically pleuritic in pattern, the chest discomfort associated with pulmonary embolism may result from (1) involvement of the pleural surface of the lung adjacent to a resultant pulmonary infarction; (2) distention of the pulmonary artery; or (3) possibly, right ventricular wall stress and/or subendocardial ischemia related to acute pulmonary hypertension. The pain associated with small pulmonary emboli is often lateral and pleuritic and is believed to be related to the first of these three possible mechanisms. In contrast, massive pulmonary emboli may cause severe substernal pain that may mimic an MI and that is plausibly attributed to the second and third of these potential mechanisms. Massive or submassive pulmonary embolism may also be associated with syncope, hypotension, and signs of right heart failure. Other typical


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InternalMed_Harrison. to the second and third of these potential mechanisms. Massive or submassive pulmonary embolism may also be associated with syncope, hypotension, and signs of right heart failure. Other typical characteristics that aid in the recognition of pulmonary embolism are discussed later in this chapter (see “Approach to the Patient”).


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InternalMed_Harrison. PNEUMOTHORAX (See also Chap. 317) Primary spontaneous pneumothorax is a rare cause of chest discomfort, with an estimated annual incidence in the United States of 7 per 100,000 among men and <2 per 100,000 among women. Risk factors include male sex, smoking, family history, and Marfan syndrome. The symptoms are usually sudden in onset, and dyspnea may be mild; thus, presentation to medical attention is sometimes delayed. Secondary spontaneous pneumothorax may occur in patients with underlying lung disorders, such as chronic obstructive pulmonary disease, asthma, or cystic fibrosis, and usually produces symptoms that are more severe. Tension pneumothorax is a medical emergency caused by trapped intrathoracic air that precipitates hemodynamic collapse.


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InternalMed_Harrison. Other Pulmonary Parenchymal, Pleural, or Vascular Disease (See also Chaps. 304, 305, and 316) Most pulmonary diseases that produce chest pain, including pneumonia and malignancy, do so because of involvement of the pleura or surrounding structures. Pleurisy is typically described as a knifelike pain that is worsened by inspiration or coughing. In contrast, chronic pulmonary hypertension can manifest as chest pain that may be very similar to angina in its characteristics, suggesting right ventricular myocardial ischemia in some cases. Reactive airways diseases similarly can cause chest tightness associated with breathlessness rather than pleurisy.


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InternalMed_Harrison. NON-CARDIOPuLMONARY CAuSES gastrointenstinal Conditions (See also Chap. 344) Gastrointestinal disorders are the most common cause of nontraumatic chest discomfort and often produce symptoms that are difficult to discern from more serious causes of chest pain, including myocardial ischemia. Esophageal disorders, in particular, may simulate angina in the character and location of the pain. Gastroesophageal reflux and disorders of esophageal motility are common and should be considered in the differential diagnosis of chest pain (Fig. 19-1 and Table 19-1). Acid reflux often causes a burning discomfort. The pain of esophageal spasm, in contrast, is commonly an intense, squeezing discomfort that is retrosternal in location and, like angina, may be relieved by nitroglycerin or dihydropyridine calcium channel antagonists. Chest pain can also result from injury to the esophagus, such as a Mallory-Weiss tear or even an esophageal rupture (Boerhaave syndrome) caused by severe vomiting. Peptic


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InternalMed_Harrison. calcium channel antagonists. Chest pain can also result from injury to the esophagus, such as a Mallory-Weiss tear or even an esophageal rupture (Boerhaave syndrome) caused by severe vomiting. Peptic ulcer disease is most commonly epigastric in location but can radiate into the chest (Table 19-1).


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InternalMed_Harrison. Hepatobiliary disorders, including cholecystitis and biliary colic, may mimic acute cardiopulmonary diseases. Although the pain arising from these disorders usually localizes to the right upper quadrant of the abdomen, it is variable and may be felt in the epigastrium and radiate to the back and lower chest. This discomfort is sometimes referred to the scapula or may in rare cases be felt in the shoulder, suggesting diaphragmatic irritation. The pain is steady, usually lasts several hours, and subsides spontaneously, without symptoms between attacks. Pain resulting from pancreatitis is typically aching epigastric pain that radiates to the back. Musculoskeletal and Other Causes (See also Chap. 393) Chest discomfort can be produced by any musculoskeletal disorder involving the chest wall or the nerves of the chest wall, neck, or upper limbs. PART 2 Cardinal Manifestations and Presentation of Diseases


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InternalMed_Harrison. PART 2 Cardinal Manifestations and Presentation of Diseases Costochondritis causing tenderness of the costochondral junctions (Tietze’s syndrome) is relatively common. Cervical radiculitis may manifest as a prolonged or constant aching discomfort in the upper chest and limbs. The pain may be exacerbated by motion of the neck. Occasionally, chest pain can be caused by compression of the brachial plexus by the cervical ribs, and tendinitis or bursitis involving the left shoulder may mimic the radiation of angina. Pain in a dermatomal distribution can also be caused by cramping of intercostal muscles or by herpes zoster (Chap. 217). Emotional and Psychiatric Conditions As many as 10% of patients who present to emergency departments with acute chest discomfort have a panic disorder or related condition (Table 19-1). The symptoms may include chest tightness or aching that is associated with a sense of anxiety and difficulty breathing. The symptoms may be prolonged or fleeting.


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APPROACH TO THE PATIENT:

InternalMed_Harrison. APPROACH TO THE PATIENT:


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InternalMed_Harrison. Given the broad set of potential causes and the heterogeneous risk of serious complications in patients who present with acute nontraumatic chest discomfort, the priorities of the initial clinical encounter include assessment of (1) the patient’s clinical stability and (2) the probability that the patient has an underlying cause of the discomfort that may be life-threatening. The high-risk conditions of principal concern are acute cardiopulmonary processes, including ACS, acute aortic syndrome, pulmonary embolism, tension pneumothorax, and pericarditis with tamponade. Among non-cardiopulmonary causes of chest pain, esophageal rupture likely holds the greatest urgency for diagnosis. Patients with these conditions may deteriorate rapidly despite initially appearing well. The remaining population with non-cardiopulmonary conditions has a more favorable prognosis during completion of the diagnostic work-up. A rapid targeted assessment for a serious cardiopulmonary cause is of particular


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InternalMed_Harrison. with non-cardiopulmonary conditions has a more favorable prognosis during completion of the diagnostic work-up. A rapid targeted assessment for a serious cardiopulmonary cause is of particular relevance for patients with acute ongoing pain who have presented for emergency evaluation. Among patients presenting in the outpatient setting with chronic pain or pain that has resolved, a general diagnostic assessment is reasonably undertaken (see “Outpatient Evaluation of Chest Discomfort,” below). A series of questions that can be used to structure the clinical evaluation of patients with chest discomfort is shown in Table 19-2.


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InternalMed_Harrison. 1. Could the chest discomfort be due to an acute, potentially life-threatening condition that warrants urgent evaluation and management? 2. If not, could the discomfort be due to a chronic condition likely to lead to serious complications? 3. If not, could the discomfort be due to an acute condition that warrants specific treatment? 4. If not, could the discomfort be due to another treatable chronic condition? Esophageal reflux Cervical disk disease Esophageal spasm Arthritis of the shoulder or spine Peptic ulcer disease Costochondritis Gallbladder disease Other musculoskeletal disorders Other gastrointestinal conditions Anxiety state Source: Developed by Dr. Thomas H. Lee for the 18th edition of Harrison’s Principles of Internal Medicine.


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InternalMed_Harrison. Source: Developed by Dr. Thomas H. Lee for the 18th edition of Harrison’s Principles of Internal Medicine. The evaluation of nontraumatic chest discomfort relies heavily on the clinical history and physical examination to direct subsequent diagnostic testing. The evaluating clinician should assess the quality, location (including radiation), and pattern (including onset and duration) of the pain as well as any provoking or alleviating factors. The presence of associated symptoms may also be useful in establishing a diagnosis.


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InternalMed_Harrison. Quality of Pain The quality of chest discomfort alone is never sufficient to establish a diagnosis. However, the characteristics of the pain are pivotal in formulating an initial clinical impression and assessing the likelihood of a serious cardiopulmonary process (Table 19-1), including acs in particular (Fig. 19-2). Pressure or tightness is consistent with a typical presentation of myocardial ischemic pain. Nevertheless, the clinician must remember that some patients with ischemic chest symptoms deny any “pain” but rather complain of dyspnea or a vague sense of anxiety. The severity of the discomfort has poor diagnostic accuracy. It is often helpful to ask about the similarity of the discomfort to previous definite ischemic symptoms. It is unusual for angina to be sharp, as in knifelike, stabbing, or pleuritic; however, patients sometimes use the word “sharp” to convey the intensity of discomfort rather than the quality. Pleuritic discomfort is suggestive of a process involving the


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InternalMed_Harrison. stabbing, or pleuritic; however, patients sometimes use the word “sharp” to convey the intensity of discomfort rather than the quality. Pleuritic discomfort is suggestive of a process involving the pleura, including pericarditis, pulmonary embolism, or pulmonary parenchymal processes. Less frequently, the pain of pericarditis or massive pulmonary embolism is a steady severe pressure or aching that can be difficult to discriminate from myocardial ischemia. “Tearing” or “ripping” pain is often described by patients with acute aortic dissection. However, acute aortic emergencies also present commonly with severe, knifelike pain. A burning quality can suggest acid reflux or peptic ulcer disease but may also occur with myocardial ischemia. Esophageal pain, particularly with spasm, can be a severe squeezing discomfort identical to angina.


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InternalMed_Harrison. Location of Discomfort A substernal location with radiation to the neck, jaw, shoulder, or arms is typical of myocardial ischemic discomfort. Some patients present with aching in sites of radiated pain as their only symptoms of ischemia. However, pain that is highly localized—e.g., that which can be demarcated by the tip of one finger—is highly unusual for angina. A retrosternal location should prompt consideration of esophageal pain; however, other gastrointestinal conditions usually present with pain that is most intense in the abdomen or epigastrium, with possible radiation into the chest. Angina may also occur in an epigastric location. However, pain that occurs solely above the mandible or below the epigastrium is rarely angina. Severe pain radiating to the back, particularly between the shoulder blades, should prompt consideration of an acute aortic syndrome. Radiation to the trapezius ridge is characteristic of pericardial pain and does not usually occur with angina.


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InternalMed_Harrison. Pattern Myocardial ischemic discomfort usually builds over minutes and is exacerbated by activity and mitigated by rest. In contrast, pain that reaches its peak intensity immediately is more suggestive of aortic dissection, pulmonary embolism, or spontaneous pneumothorax. Pain that is fleeting (lasting only a few seconds) is rarely ischemic in origin. Similarly, pain that is constant in intensity for a prolonged period (many hours to days) is unlikely to represent myocardial ischemia if it occurs in the absence of other clinical consequences, such as abnormalities of the ECG, elevation of cardiac biomarkers, or clinical sequelae (e.g., heart failure or hypotension). Both myocardial ischemia and acid reflux may have their onset in the morning, the latter because of the absence of food to absorb gastric acid.


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InternalMed_Harrison. Provoking and Alleviating Factors Patients with myocardial ischemic pain usually prefer to rest, sit, or stop walking. However, clinicians should be aware of the phenomenon of “warm-up angina” in which some patients experience relief of angina as they continue at the same or even a greater level of exertion without symptoms (Chap. 293). Alterations in the intensity of pain with changes in position or movement of the upper extremities and neck are less likely with myocardial ischemia and suggest a musculoskeletal etiology. The pain of pericarditis, however, often is worse in the supine position and relieved by sitting upright and leaning forward. Gastroesophageal reflux may be exacerbated by alcohol, some foods, or by a reclined position. Relief can occur with sitting.


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InternalMed_Harrison. Radiation to right arm or shoulder Radiation to both arms or shoulders Associated with exertion Radiation to left arm Associated with diaphoresis Associated with nausea or vomiting Worse than previous angina or similar to previous MI Described as pressure Inframammary location Reproducible with palpation Described as sharp Described as positional Described as pleuritic 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 FIguRE 19-2 Association of chest pain characteristics with the probability of acute myocardial infarction (AMI). (Figure prepared from data in CJ Swap, JT Nagurney: JAMA 294:2623, 2005.)


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InternalMed_Harrison. Exacerbation by eating suggests a gastrointestinal etiology such as peptic ulcer disease, cholecystitis, or pancreatitis. Peptic ulcer disease tends to become symptomatic 60–90 min after meals. However, in the setting of severe coronary atherosclerosis, redistribution of blood flow to the splanchnic vasculature after eating can trigger postprandial angina. The discomfort of acid reflux and peptic ulcer disease is usually diminished promptly by acid-reducing therapies. In contrast with its impact in some patients with angina, physical exertion is very unlikely to alter symptoms from gastrointestinal causes of chest pain. Relief of chest discomfort within minutes after administration of nitroglycerin is suggestive of but not sufficiently sensitive or specific for a definitive diagnosis of myocardial ischemia. Esophageal spasm may also be relieved promptly with nitroglycerin. A delay of >10 min before relief is obtained after nitroglycerin suggests that the symptoms either are not caused


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InternalMed_Harrison. ischemia. Esophageal spasm may also be relieved promptly with nitroglycerin. A delay of >10 min before relief is obtained after nitroglycerin suggests that the symptoms either are not caused by ischemia or are caused by severe ischemia, such as during acute MI.


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InternalMed_Harrison. Associated Symptoms Symptoms that accompany myocardial ischemia may include diaphoresis, dyspnea, nausea, fatigue, faintness, and eructations. In addition, these symptoms may exist in isolation as anginal equivalents (i.e., symptoms of myocardial ischemia other than typical angina), particularly in women and the elderly. Dyspnea may occur with multiple conditions considered in the differential diagnosis of chest pain and thus is not discriminative, but the presence of dyspnea is important because it suggests a cardiopulmonary etiology. Sudden onset of significant respiratory distress should lead to consideration of pulmonary embolism and spontaneous pneumothorax. Hemoptysis may occur with pulmonary embolism, or as blood-tinged frothy sputum in severe heart failure but usually points toward a pulmonary parenchymal etiology of chest symptoms. Presentation with syncope or pre-syncope should prompt consideration of hemodynamically significant pulmonary embolism or aortic dissection as


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InternalMed_Harrison. a pulmonary parenchymal etiology of chest symptoms. Presentation with syncope or pre-syncope should prompt consideration of hemodynamically significant pulmonary embolism or aortic dissection as well as ischemic arrhythmias. Although nausea and vomiting suggest a gastrointestinal disorder, these symptoms may occur in the setting of MI (more commonly inferior MI), presumably because of activation of the vagal reflex or stimulation of left ventricular receptors as part of the Bezold-Jarisch reflex.


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InternalMed_Harrison. Past Medical History The past medical history is useful in assessing the patient for risk factors for coronary atherosclerosis (Chap. 291e) and venous thromboembolism (Chap. 300) as well as for conditions that may predispose the patient to specific disorders. For example, a history of connective tissue diseases such as marfan syndrome should heighten the clinician’s suspicion of an acute aortic syndrome or spontaneous pneumothorax. A careful history may elicit clues about depression or prior panic attacks.


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InternalMed_Harrison. In addition to providing an initial assessment of the patient’s clinical stability, the physical examination of patients with chest discomfort can provide direct evidence of specific etiologies of chest pain (e.g., unilateral absence of lung sounds) and can identify potential precipitants of acute cardiopulmonary causes of chest pain (e.g., uncontrolled hypertension), relevant comorbid conditions (e.g., obstructive pulmonary disease), and complications of the presenting syndrome (e.g., heart failure). However, because the findings on physical examination may be normal in patients with unstable ischemic heart disease, an unremarkable physical exam is not definitively reassuring.


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InternalMed_Harrison. general The patient’s general appearance is helpful in establishing an initial impression of the severity of illness. Patients with acute MI or other acute cardiopulmonary disorders often appear anxious, uncomfortable, pale, cyanotic, or diaphoretic. Patients who are massaging or clutching their chests may describe their pain with a clenched fist held against the sternum (Levine’s sign). Occasionally, body habitus is helpful—e.g., in patients with Marfan syndrome or the prototypical young, tall, thin man with spontaneous pneumothorax. PART 2 Cardinal Manifestations and Presentation of Diseases


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InternalMed_Harrison. PART 2 Cardinal Manifestations and Presentation of Diseases Vital Signs Significant tachycardia and hypotension are indicative of important hemodynamic consequences of the underlying cause of chest discomfort and should prompt a rapid survey for the most severe conditions, such as acute MI with cardiogenic shock, massive pulmonary embolism, pericarditis with tamponade, or tension pneumothorax. Acute aortic emergencies usually present with severe hypertension but may be associated with profound hypotension when there is coronary arterial compromise or dissection into the pericardium. Sinus tachycardia is an important manifestation of submassive pulmonary embolism. Tachypnea and hypoxemia point toward a pulmonary cause. The presence of low-grade fever is nonspecific because it may occur with MI and with thromboembolism in addition to infection.


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InternalMed_Harrison. Pulmonary Examination of the lungs may localize a primary pulmonary cause of chest discomfort, as in cases of pneumonia, asthma, or pneumothorax. Left ventricular dysfunction from severe ischemia/infarction as well as acute valvular complications of MI or aortic dissection can lead to pulmonary edema, which is an indicator of high risk.


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InternalMed_Harrison. Cardiac The jugular venous pulse is often normal in patients with acute myocardial ischemia but may reveal characteristic patterns with pericardial tamponade or acute right ventricular dysfunction (Chaps. 267 and 288). Cardiac auscultation may reveal a third or, more commonly, a fourth heart sound, reflecting myocardial systolic or diastolic dysfunction. Murmurs of mitral regurgitation or a harsh murmur of a ventricular-septal defect may indicate mechanical complications of STEMI. A murmur of aortic insufficiency may be a complication of proximal aortic dissection. Other murmurs may reveal underlying cardiac disorders contributory to ischemia (e.g., aortic stenosis or hypertrophic cardiomyopathy). Pericardial friction rubs reflect pericardial inflammation.


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InternalMed_Harrison. Abdominal Localizing tenderness on the abdominal exam is useful in identifying a gastrointestinal cause of the presenting syndrome. Abdominal findings are infrequent with purely acute cardiopulmonary problems, except in the case of underlying chronic cardiopulmonary disease or severe right ventricular dysfunction leading to hepatic congestion. Vascular Pulse deficits may reflect underlying chronic atherosclerosis, which increases the likelihood of coronary artery disease. However, evidence of acute limb ischemia with loss of the pulse and pallor, particularly in the upper extremities, can indicate catastrophic consequences of aortic dissection. Unilateral lower-extremity swelling should raise suspicion about venous thromboembolism.


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InternalMed_Harrison. Musculoskeletal Pain arising from the costochondral and chondrosternal articulations may be associated with localized swelling, redness, or marked localized tenderness. Pain on palpation of these joints is usually well localized and is a useful clinical sign, though deep palpation may elicit pain in the absence of costochondritis. Although palpation of the chest wall often elicits pain in patients with various musculoskeletal conditions, it should be appreciated that chest wall tenderness does not exclude myocardial ischemia. Sensory deficits in the upper extremities may be indicative of cervical disk disease.


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InternalMed_Harrison. Electrocardiography is crucial in the evaluation of nontraumatic chest discomfort. The ECG is pivotal for identifying patients with ongoing ischemia as the principal reason for their presentation as well as secondary cardiac complications of other disorders. Professional society guidelines recommend that an ECG be obtained within 10 min of presentation, with the primary goal of identifying patients with ST-segment elevation diagnostic of MI who are candidates for immediate interventions to restore flow in the occluded coronary artery. ST-segment depression and symmetric T-wave inversions at least 0.2 mV in depth are useful for detecting myocardial ischemia in the absence of STEMI and are also indicative of higher risk of death or recurrent ischemia. Serial performance of ECGs (every 30–60 min) is recommended in the ED evaluation of suspected ACS. In addition, an ECG with right-sided lead placement should be considered in patients with clinically suspected ischemia and a nondiagnostic


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InternalMed_Harrison. min) is recommended in the ED evaluation of suspected ACS. In addition, an ECG with right-sided lead placement should be considered in patients with clinically suspected ischemia and a nondiagnostic standard 12-lead ECG. Despite the value of the resting ECG, its sensitivity for ischemia is poor—as low as 20% in some studies.


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InternalMed_Harrison. Abnormalities of the ST segment and T wave may occur in a variety of conditions, including pulmonary embolism, ventricular hypertrophy, acute and chronic pericarditis, myocarditis, electrolyte imbalance, and metabolic disorders. Notably, hyperventilation associated with panic disorder can also lead to nonspecific ST and T-wave abnormalities. Pulmonary embolism is most often associated with sinus tachycardia but can also lead to rightward shift of the ECG axis, manifesting as an S-wave in lead I, with a Q-wave and T-wave in lead III (Chaps. 268 and 300). In patients with ST-segment elevation, the presence of diffuse lead involvement not corresponding to a specific coronary anatomic distribution and PR-segment depression can aid in distinguishing pericarditis from acute MI.


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InternalMed_Harrison. (See Chap. 308e) Plain radiography of the chest is performed routinely when patients present with acute chest discomfort and selectively when individuals who are being evaluated as outpatients have subacute or chronic pain. The chest radiograph is most useful for identifying pulmonary processes, such as pneumonia or pneumothorax. Findings are often unremarkable in patients with ACS, but pulmonary edema may be evident. Other specific findings include widening of the mediastinum in some patients with aortic dissection, Hampton’s hump or Westermark’s sign in patients with pulmonary embolism (Chaps. 300 and 308e), or pericardial calcification in chronic pericarditis.


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InternalMed_Harrison. Laboratory testing in patients with acute chest pain is focused on the detection of myocardial injury. Such injury can be detected by the presence of circulating proteins released from damaged myocardial cells. Owing to the time necessary for this release, initial biomarkers of injury may be in the normal range, even in patients with STEMI. Because of superior cardiac tissue-specificity compared with creatine kinase MB, cardiac troponin is the preferred biomarker for the diagnosis of MI and should be measured in all patients with suspected ACS at presentation and repeated in 3–6 h. Testing after 6 h is required only when there is uncertainty regarding the onset of pain or when stuttering symptoms have occurred. It is not necessary or advisable to measure troponin in patients without suspicion of ACS unless this test is being used specifically for risk stratification (e.g., in pulmonary embolism or heart failure).


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InternalMed_Harrison. The development of cardiac troponin assays with progressively greater analytical sensitivity has facilitated detection of substantially lower blood concentrations of troponin than was previously possible. This evolution permits earlier detection of myocardial injury, enhances the overall accuracy of a diagnosis of MI, and improves risk stratification in suspected ACS. The greater negative predictive value of a negative troponin result with current-generation assays is an advantage in the evaluation of chest pain in the ED. Rapid rule-out protocols that use serial testing and changes in troponin concentration over as short a period as 1–2 h appear promising and remain under investigation. However, with these advantages has come a trade-off: myocardial injury is detected in a larger proportion of patients who have non-ACS cardiopulmonary conditions than with previous, less sensitive assays. This evolution in testing for myocardial necrosis has rendered other aspects of the clinical


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InternalMed_Harrison. of patients who have non-ACS cardiopulmonary conditions than with previous, less sensitive assays. This evolution in testing for myocardial necrosis has rendered other aspects of the clinical evaluation critical to the practitioner’s determination of the probability that the symptoms represent ACS. In addition, observation of a change in cardiac troponin concentration between serial samples is useful in discriminating acute causes of myocardial injury from chronic elevation due to underlying structural heart disease, end-stage renal disease, or interfering antibodies. The diagnosis of MI is reserved for acute myocardial injury that is marked by a rising and/or falling pattern—with at least one value exceeding the 99th percentile reference limit—and that is caused by ischemia. Other non-ischemic insults, such as myocarditis, may result in myocardial injury but should not be labeled MI.


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InternalMed_Harrison. Other laboratory assessments may include the D-dimer test to aid in exclusion of pulmonary embolism (Chap. 300). Measurement of a B-type natriuretic peptide is useful when considered in conjunction with the clinical history and exam for the diagnosis of heart failure. B-type natriuretic peptides also provide prognostic information regarding patients with ACS and those with pulmonary embolism. Other putative biomarkers of acute myocardial ischemia or ACS, such as myeloperoxidase, have not been adopted in routine use.


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InternalMed_Harrison. Multiple clinical algorithms have been developed to aid in decision-making during the evaluation and disposition of patients with acute nontraumatic chest pain. Such decision-aids have been derived on the basis of their capacity to estimate either of two closely related but not identical probabilities: (1) the probability of a final diagnosis of ACS and (2) the probability of major cardiac events during short-term follow-up. Such decision-aids are used most commonly to identify patients with a low clinical probability of ACS who are candidates either for early provocative testing for ischemia or for discharge from the ED. Goldman and Lee developed one of the first such decision-aids, using only the ECG and risk indicators—hypotension, pulmonary rales, and known ischemic heart disease—to categorize patients into four risk categories ranging from a <1% to a >16% probability of a major cardiovascular complication. The Acute Cardiac Ischemia Time-Insensitive Predictive Instrument


InternalMed_Harrison

InternalMed_Harrison. categorize patients into four risk categories ranging from a <1% to a >16% probability of a major cardiovascular complication. The Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI) combines age, sex, chest pain presence, and ST-segment abnormalities to define a probability of ACS. More recently developed decision-aids are shown in Fig. 19-3. Elements common to each of these tools are (1) symptoms typical for ACS; (2) older age; (3) risk factors for or known atherosclerosis; (4) ischemic ECG abnormalities; and (5) elevated cardiac troponin levels. Although, because of very low specificity, the overall diagnostic performance of such decision-aids is poor (area under the receiver operating curve, 0.55–0.65), they can help identify patients with a very low probability of ACS (e.g., <1%). Nevertheless, no such decision-aid (or single clinical factor) is sufficiently sensitive and well validated to use as a sole tool for clinical decision-making.


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InternalMed_Harrison. Clinicians should differentiate between the algorithms discussed above and risk scores derived for stratification of prognosis (e.g., the TIMI and GRACE risk scores, Chap. 295) in patients who already have an established diagnosis of ACS. The latter risk scores were not designed to be used for diagnostic assessment.


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InternalMed_Harrison. Exercise electrocardiography (“stress testing”) is commonly employed for completion of risk stratification of patients who have undergone an initial evaluation that has not revealed a specific cause of chest discomfort and has identified them as being at low or selectively intermediate risk of ACS. Early exercise testing is safe in patients without high-risk findings after 8–12 h of observation and can assist in refining their prognostic assessment. For example, of low-risk patients who underwent exercise testing in the first 48 h after presentation, those without evidence of ischemia had a 2% rate of cardiac events through 6 months, whereas the rate was 15% among patients with either clear evidence of ischemia or an equivocal result. Patients who are unable to exercise may undergo pharmacological stress testing with either nuclear perfusion imaging or echocardiography. Notably, some experts have deemed the routine use of stress testing for low-risk patients unsupported by direct


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InternalMed_Harrison. stress testing with either nuclear perfusion imaging or echocardiography. Notably, some experts have deemed the routine use of stress testing for low-risk patients unsupported by direct clinical evidence and a potentially unnecessary source of cost.


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InternalMed_Harrison. Professional society guidelines identify ongoing chest pain as a contraindication to stress testing. In selected patients with persistent pain and nondiagnostic ECG and biomarker data, resting PART 2 Cardinal Manifestations and Presentation of Diseases HEART Score History Highly suspicious Moderately suspicious Slightly suspicious 2 1 0 ECG Significant ST-depression Non-specific abnormality Normal 2 1 0 Age 65 y 45–<65 y <45 y 2 1 0 Risk factors 3 risk factors 1–2 risk factors None 2 1 0 Troponin (serial) 3 × 99th percentile 1–<3 × 99th percentile �99th percentile 2 1 0 TOTAL Low-risk: 0–3 Not low risk: 4 North American Chest Pain Rule High Risk Criteria Y/N Typical symptoms for ischemia ECG: acute ischemic changes Age 50 y Known coronary artery disease Troponin (serial) >99th percentile Low-risk: All No Not Low-risk: Any Yes 20.2Captured as low-risk (%) 4.4 Sensitivity 99.1 100 Specificity 25.7 5.6


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InternalMed_Harrison. Sensitivity 99.1 100 Specificity 25.7 5.6 FIguRE 19-3 Examples of decision-aids used in conjunction with serial measurement of cardiac troponin for evaluation of acute chest pain. (Figure prepared from data in SA Mahler et al: Int J Cardiol 168:795, 2013.) myocardial perfusion images can be obtained; the absence of any perfusion abnormality substantially reduces the likelihood of coronary artery disease. In some centers, early myocardial perfusion imaging is performed as part of a routine strategy for evaluating patients at low or intermediate risk of ACS in parallel with other testing. Management of patients with normal perfusion images can be expedited with earlier discharge and outpatient stress testing, if indicated. Those with abnormal rest perfusion imaging, which cannot discriminate between old or new myocardial defects, must undergo additional in-hospital evaluation.


InternalMed_Harrison

InternalMed_Harrison. Other noninvasive imaging studies of the chest can be used selectively to provide additional diagnostic and prognostic information on patients with chest discomfort. Echocardiography Echocardiography is not necessarily routine in patients with chest discomfort. However, in patients with an uncertain diagnosis, particularly those with nondiagnostic ST elevation, ongoing symptoms, or hemodynamic instability, detection of abnormal regional wall motion provides evidence of possible ischemic dysfunction. Echocardiography is diagnostic in patients with mechanical complications of MI or in patients with pericardial tamponade. Transthoracic echocardiography is poorly sensitive for aortic dissection, although an intimal flap may sometimes be detected in the ascending aorta.


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InternalMed_Harrison. CT Angiography (See Chap. 270e) CT angiography is emerging as a modality for the evaluation of patients with acute chest discomfort. Coronary CT angiography is a sensitive technique for detection of obstructive coronary disease, particularly in the proximal third of the major epicardial coronary arteries. CT appears to enhance the speed to disposition of patients with a low-intermediate probability for ACS; its major strength being the negative predictive value of a finding of no significant disease. In addition, contrast-enhanced CT can detect focal areas of myocardial injury in the acute setting as decreased areas of enhancement. At the same time, CT angiography can exclude aortic dissection, pericardial effusion, and pulmonary embolism. Balancing factors in the consideration of the emerging role of coronary CT angiography in low-risk patients are radiation exposure and additional testing prompted by nondiagnostic abnormal results.


InternalMed_Harrison

InternalMed_Harrison. MRI (See Chap. 270e) Cardiac magnetic resonance (CMR) imaging is an evolving, versatile technique for structural and functional evaluation of the heart and the vasculature of the chest. CMR accurately measures ventricular dimensions and function and can be performed as a modality for pharmacologic stress perfusion imaging. Gadolinium-enhanced CMR can provide early detection of MI, defining areas of myocardial necrosis accurately, and can delineate patterns of myocardial disease that are often useful in discriminating ischemic from non-ischemic myocardial injury. Although usually not practical for the urgent evaluation of acute chest discomfort, CMR can be a useful modality for cardiac structural evaluation of patients with elevated cardiac troponin levels in the absence of definite coronary artery disease. CMR coronary angiography is in its early stages. MRI also permits highly accurate assessment for aortic dissection but is infrequently used as the first test because CT and


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InternalMed_Harrison. coronary artery disease. CMR coronary angiography is in its early stages. MRI also permits highly accurate assessment for aortic dissection but is infrequently used as the first test because CT and transesophageal echocardiography are usually more practical.


InternalMed_Harrison

InternalMed_Harrison. Because of the challenges inherent in reliably identifying the small proportion of patients with serious causes of acute chest discomfort while not exposing the larger number of low-risk patients to unnecessary testing and extended ED or hospital evaluations, many medical centers have adopted critical pathways to expedite the assessment and management of patients with nontraumatic chest pain, often in dedicated chest pain units. Such pathways are generally aimed at (1) rapid identification, triage, and treatment of high-risk cardiopulmonary conditions (e.g., STEMI); (2) accurate identification of low-risk patients who can be safely observed in units with less intensive monitoring, undergo early exercise testing, or be discharged home; and (3) through more efficient and systematic accelerated diagnostic protocols, safe reduction in costs associated with overuse of testing and unnecessary hospitalizations. In some studies, provision of pro-tocol-driven care in chest pain units has


InternalMed_Harrison

InternalMed_Harrison. diagnostic protocols, safe reduction in costs associated with overuse of testing and unnecessary hospitalizations. In some studies, provision of pro-tocol-driven care in chest pain units has decreased costs and overall duration of hospital evaluation with no detectable excess of adverse clinical outcomes.


InternalMed_Harrison

InternalMed_Harrison. Chest pain is common in outpatient practice, with a lifetime prevalence of 20–40% in the general population. More than 25% of patients with MI have had a related visit with a primary care physician in the previous month. The diagnostic principles are the same as in the ED. However, the pretest probability of an acute cardiopulmonary cause is significantly lower. Therefore, testing paradigms are less intense, with an emphasis on the history, physical examination, and ECG. Moreover, decision-aids developed for settings with a high prevalence of significant cardiopulmonary disease have lower positive predictive value when applied in the practitioner’s office. However, in general, if the level of clinical suspicion of ACS is sufficiently high to consider troponin testing, the patient should be referred to the ED for evaluation.


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InternalMed_Harrison. Abdominal Pain Danny O. Jacobs, William Silen Correctly interpreting acute abdominal pain can be quite challenging. Few clinical situations require greater judgment, because the most catastrophic of events may be forecast by the subtlest of symptoms and signs. In every instance, the clinician must distinguish those conditions 20 that require urgent intervention from those that do not and can best be managed nonoperatively. A meticulously executed, detailed history and physical examination are critically important for focusing the differential diagnosis, where necessary, and allowing the diagnostic evaluation to proceed expeditiously (Table 20-1). The etiologic classification in Table 20-2, although not complete, provides a useful framework for evaluating patients with abdominal pain.


InternalMed_Harrison

InternalMed_Harrison. The etiologic classification in Table 20-2, although not complete, provides a useful framework for evaluating patients with abdominal pain. The most common causes of abdominal pain on admission are acute appendicitis, nonspecific abdominal pain, pain of urologic origin, and intestinal obstruction. A diagnosis of “acute or surgical abdomen” is not acceptable because of its often misleading and erroneous connotations. Most patients who present with acute abdominal pain will have self-limited disease processes. However, it is important to remember that pain severity does not necessarily correlate with the severity of the underlying condition. The most obvious of “acute abdomens” may SoME KEy CoMPonEnTS of THE PATiEnT’S HiSToRy


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InternalMed_Harrison. SoME KEy CoMPonEnTS of THE PATiEnT’S HiSToRy Age Time and mode of onset of the pain Pain characteristics Duration of symptoms Location of pain and sites of radiation Associated symptoms and their relationship to the pain Nausea, emesis, and anorexia Diarrhea, constipation, or other changes in bowel habits Menstrual history not require operative intervention, and the mildest of abdominal pains 103 may herald an urgently correctable lesion. Any patient with abdominal pain of recent onset requires early and thorough evaluation and accurate diagnosis.


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InternalMed_Harrison. SOME MECHANISMS OF PAIN ORIgINATINg IN THE ABDOMEN Inflammation of the Parietal Peritoneum The pain of parietal peritoneal inflammation is steady and aching in character and is located directly over the inflamed area, its exact reference being possible because it is transmitted by somatic nerves supplying the parietal peritoneum. The intensity of the pain is dependent on the type and amount of material to which the peritoneal surfaces are exposed in a given time period. For example , the sudden release into the peritoneal cavity of a small quantity of sterile acid gastric juice causes much more pain than the same amount of grossly contaminated neutral feces. Enzymatically active pancreatic juice incites more pain and inflammation than does the same amount of sterile bile containing no potent enzymes. Blood is normally only a mild irritant and the response to urine can be bland, so exposure of blood and urine to the peritoneal cavity may go unnoticed unless it is sudden and massive.


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InternalMed_Harrison. enzymes. Blood is normally only a mild irritant and the response to urine can be bland, so exposure of blood and urine to the peritoneal cavity may go unnoticed unless it is sudden and massive. Bacterial contamination, such as may occur with pelvic inflammatory disease or perforated distal intestine, causes low-intensity pain until multiplication causes a significant amount of inflammatory mediators to be released. Patients with perforated upper gastrointestinal ulcers may present entirely differently depending on how quickly gastric juices enter the peritoneal cavity. Thus, the rate at which any inflammatory material irritates the peritoneum is important.


InternalMed_Harrison

InternalMed_Harrison. The pain of peritoneal inflammation is invariably accentuated by pressure or changes in tension of the peritoneum, whether produced by palpation or by movement such as with coughing or sneezing. The patient with peritonitis characteristically lies quietly in bed, preferring to avoid motion, in contrast to the patient with colic, who may be thrashing in discomfort.


InternalMed_Harrison

InternalMed_Harrison. Another characteristic feature of peritoneal irritation is tonic reflex spasm of the abdominal musculature, localized to the involved body segment. Its intensity depends on the integrity of the nervous system, the location of the inflammatory process, and the rate at which it develops. Spasm over a perforated retrocecal appendix or perforation into the lesser peritoneal sac may be minimal or absent because of the protective effect of overlying viscera. Catastrophic abdominal emergencies may be associated with minimal or no detectable pain or muscle spasm in obtunded, seriously ill, debilitated, immunosuppressed, or psychotic patients. A slowly developing process also often greatly attenuates the degree of muscle spasm.


InternalMed_Harrison

InternalMed_Harrison. Obstruction of Hollow Viscera Intraluminal obstruction classically elicits intermittent or colicky abdominal pain that is not as well localized as the pain of parietal peritoneal irritation. However, the absence of cramping discomfort should not be misleading because distention of a hollow viscus may also produce steady pain with only rare paroxysms. Small-bowel obstruction often presents as poorly localized, intermittent periumbilical or supraumbilical pain. As the intestine progressively dilates and loses muscular tone, the colicky nature of the pain may diminish. With superimposed strangulating obstruction, pain may spread to the lower lumbar region if there is traction on the root of the mesentery. The colicky pain of colonic obstruction is of lesser intensity, is commonly located in the infraumbilical area, and may often radiate to the lumbar region.


InternalMed_Harrison

InternalMed_Harrison. Sudden distention of the biliary tree produces a steady rather than colicky type of pain; hence, the term biliary colic is misleading. Acute distention of the gallbladder usually causes pain in the right upper quadrant with radiation to the right posterior region of the thorax or to the tip of the right scapula, but it is also not uncommonly found near the midline. Distention of the common bile duct often causes epigastric pain that may radiate to the upper lumbar region. Considerable variation is common, however, so that differentiation between these may be impossible. The typical subscapular pain or lumbar radiation is frequently absent. Gradual dilatation of the biliary tree, as can occur with carcinoma of the head of the pancreas, may cause no pain Pain Originating in the Abdomen PART 2 Cardinal Manifestations and Presentation of Diseases


InternalMed_Harrison

InternalMed_Harrison. Pain Originating in the Abdomen PART 2 Cardinal Manifestations and Presentation of Diseases Mechanical obstruction of hollow viscera Obstruction of the small or large intestine Obstruction of the biliary tree Obstruction of the ureter Abdominal wall Distortion or traction of mesentery Trauma or infection of muscles Distension of visceral surfaces, e.g., by hemorrhage Hepatic or renal capsules or only a mild aching sensation in the epigastrium or right upper quadrant. The pain of distention of the pancreatic ducts is similar to that described for distention of the common bile duct but, in addition, is very frequently accentuated by recumbency and relieved by the upright position.


InternalMed_Harrison

InternalMed_Harrison. Obstruction of the urinary bladder usually causes dull, low-intensity pain in the suprapubic region. Restlessness without specific complaint of pain may be the only sign of a distended bladder in an obtunded patient. In contrast, acute obstruction of the intravesicular portion of the ureter is characterized by severe suprapubic and flank pain that radiates to the penis, scrotum, or inner aspect of the upper thigh. Obstruction of the ureteropelvic junction manifests as pain near the costovertebral angle, whereas obstruction of the remainder of the ureter is associated with flank pain that often extends into the same side of the abdomen.