Noncardiac Chest Pain Educational Objectives Faculty Disclosure

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Noncardiac Chest Pain Educational Objectives Faculty Disclosure Powered By Docstoc
					Volume 24, Issue 03                                                                                                February 7, 2010

                                          SOURCES OF GASTROINTESTINAL PAIN
Noncardiac Chest Pain                                                 pH and impedance probes; indicated in patient on PPI with
                                                                      persistent CP; if test positive and shows reflux with acid,
Evan S. Dellon, MD, MPH, Assistant Professor of Medi-                 means reflux acid-mediated; if reflux seen but no acid, reflux
cine, Division of Gastroenterology and Hepatology, Uni-               nonacid; if pH impedance negative, symptoms not due to re-
versity of North Carolina School of Medicine, Chapel Hill             flux disease
Noncardiac chest pain (NCCP): definition — recurrent                Esophageal manometry: detects underlying motility disor-
  retrosternal pain or discomfort of noncardiac etiology; com-        ders; performed after excluding reflux disease and if clinical
  mon and nonspecific; multiple causes; typically, history and        suspicion for esophageal dysmotility present; 2 studies —
  physical examination (PE) not helpful                               looked at patients with NCCP and nonreflux CP with esoph-
Causes of NCCP: rule out cardiac causes; gastroesophageal             ageal motility studies; found 25% had abnormal motility
  reflux disease (GERD) most common gastrointestinal (GI)             studies, indicating underlying motility disorder; specific con-
  cause; erosive and nonerosive disease account for 50% of           ditions found included “nutcracker” esophagus, achalasia,
  all cases of NCCP; esophageal dysmotility, 15%-25%; func-           and diffuse esophageal spasm; overall, motility disorders ac-
  tional CP, 30% to 40%                                               count for 20% to 25% of NCCP; barium swallow — several
Upper endoscopy: indicated if alarm symptoms present in his-          simultaneous contractions in esophagus with corkscrew ap-
  tory and PE; alarm symptoms include dysphagia, odynopha-            pearance indicative of diffuse esophageal spasms; differenti-
  gia, anemia, weight loss, GI bleeding, and new onset of             ated from “nutcracker” esophagus (pressure >180 mm Hg)
  symptoms in older patients; also indicated if structural lesion   Functional CP: second most common cause of NCCP; probably
  that would chang management strongly suspected; findings            underdiagnosed formally; Rome III definition (requires all
  limited to structural lesions; low yield in NCCP; study —           three characteristics) — 1) midline CP or discomfort not of
   retrospective look at endoscopies and their indications and        burning quality; 2) absence of evidence that gastroesophageal
  findings; malignancy found in 0.2% of participants with             reflux cause of symptom; 3) absence of histopathology-based
  NCCP; 44% had normal endoscopy; few differences seen                esophageal motility disorders; functional heartburn —
  when findings compared to those of GERD group; esophago-            distinguished from functional CP by quality of discomfort; in
  gastroduodenoscopy (EGD) also low yield for GERD; yield             functional CP, pain, pressure, or aching present; in functional
  slightly increased for esophageal inflammation and hiatal           heartburn, discomfort burning in quality; pathophysiology —
  hernia, but low yield overall in NCCP                               visceral hypersensitivity; studies of esophagus demonstrate in-
Trial of proton pump inhibitor (PPI): rationale that GERD             creased sensitivity of patient to balloon dilation and electrical
  most common cause of NCCP; most of EGD findings related             stimulation of esophagus; altered central nervous system
  to GERD; PPI used diagnostically and therapeutically; good          (CNS) processing of painful stimuli also present; comorbid
  noninvasive first-line option; cost-effective; meta-analyses        psychologic disease possibly present
  showed reasonable pooled sensitivity and specificity for cor-     Management: depends on underlying problem (motility, spasm,
  rect diagnosis of NCCP if response to PPI present (although         or functional CP); reassurance and explanation of diagnosis
  not perfect); effective for treatment, compared to placebo;         crucial (first action); centrally acting medications quite effec-
  before prescribing PPI, exclude cardiac disease and ensure          tive in modulating pain in both conditions, even in spasm; anti-
  that no alarm symptoms present; typically, high-dose PPI            cholinergics and antispasmodics play role as possible first-line
  recommended; immaterial which PPI used, but should use 2            treatment, but data inadequate; muscle relaxants — nitrates; in-
  to 4 wk and 2 mo before assessing response                         dicated for spasm; not much data, with inconsistent results in
pH impedance: typically used in NCCP to evaluate role and             small open-label trials; sublingual nitroglycerin for on-demand
  type of reflux (acid or nonacid); refluxate characterized by        use, and isosorbide dinitrate for longer use; tachyphylaxis pos-

                                                    Educational Objectives
  The goal of this program is to improve the management of          this educational activity promotes quality in health care and
  noncardiac chest pain (NCCP), functional dyspepsia, and nar-      not a proprietary business or commercial interest. For this pro-
  cotic bowel syndrome (NBS). After hearing and assimilating        gram, the following has been disclosed: Dr. Drossman is a
  this program, the clinician will be better able to:               consultant for Takeda, Sucampo, and Prometheus and has re-
      1. Utilize the most appropriate test to determine the cause   ceived a research grant from Wyeth Pharmaceuticals. Drs.
          of NCCP.                                                  Dellon, Mertz, and the planning committee reported nothing to
      2. Describe the pharmacologic and nonpharmacologic            disclose. Drs. Dellon, Mertz, and Drossman present informa-
          treatment of NCCP.                                        tion that is related to off-label or investigational use of a ther-
      3. Discuss the pathophysiology of functional dyspepsia.       apy, product, or device.
      4. Recognize the typical clinical presentation of NBS.                            Acknowledgements
      5. Discuss the importance of the physician-patient rela-
          tionship in the narcotic withdrawal protocol.             Dr. Dellon was recorded at Update in Gastroenterology and
                                                                    Hepatology: Applying Sound Principles in Daily Practice,
                      Faculty Disclosure                            held April 17-19, 2009, in Chapel Hill, NC, and sponsored by
                                                                    the University of North Carolina School of Medicine, Chapel
  In adherence to ACCME Standards for Commercial Support,           Hill. Drs. Mertz and Drossman were recorded at Gastroenter-
  Audio-Digest requires all faculty and members of the planning     ology and Hepatology Update 2009, held September 11-12,
  committee to disclose relevant financial relationships within     2009, in Nashville, TN, and sponsored by the Vanderbilt Di-
  the past 12 months that might create any personal conflicts of    gestive Disease Center.
  interest. Any identified conflicts were resolved to ensure that
                                       AUDIO-DIGEST GASTROENTEROLOGY 24:03

  sible; with nitrates, trading CP for severe splitting headache;        that only patients with functional dyspepsia (FD) had low
  calcium channel blockers — inconsistent results seen in small          pain, fullness, and discomfort thresholds, compared to con-
  trials; nifedipine or diltiazem used in low doses in tid dosing or     trols; Belgian study showed duodenal hypersensitivity to
  extended-release preparations; balance side effects with treat-        acid infusion; in FD, stomach stiffer and unable to relax (ac-
  ment effects; concern about hypotension, orthostasis, dizziness,       commodate) as much after meal; delayed gastric
  and lightheadedness, as well as peripheral edema and bradycar-         emptying — found in 25% of those with FD; study found
  dia; botulinum toxin type A (Botox) — blocks release of acetyl-        that patients with delayed gastric emptying more likely to
  choline at presynaptic terminals, leading to muscle paralysis;         have postprandial fullness and vomiting; hypersensitivity to
  effective in achalasia (relaxes lower esophageal sphincter) and        distention (seen in 40% of subjects) correlates with pain,
  esophageal spasm; limited data; not permanent (lasts 3-6 mo);          belching, and weight loss; impaired accommodation —
  patient followed long-term may require repeated therapy or             correlates with early satiety and weight loss; postdysenteric
  other form of treatment; centrally acting agents — target patho-       FD — follow-up of Escherichia coli 0157:H7 outbreak
  physiology of increased pain sensation at peripheral and central       found that longer duration of diarrhea, female sex, preexpo-
  level; inadequate data; trial and error                                sure IBS, and preexposure psychologic stressors predicted
General principles of treatment: start with low dose and ti-             occurrence of FD 8 yr later (similar to IBS)
  trate as tolerated or until desired effect achieved; may not see     Anxiety in FD: survey of >2500 community dwellers in Sweden
  effects until several weeks after starting medication; impor-          found that anxiety particularly associated with FD (2.6%
  tant to educate patient and set expectations for them                  higher chance for anxious patient to have FD); postprandial
Tricyclic antidepressants (TCAs): most data for treating                 distress, not epigastric pain, particularly associated (odds ratio
  esophageal conditions; thought to modulate pain via norepi-            of 4.35); depression not associated with FD; nonsteroidal anti-
  nephrine and serotonergic effects; several receptor effects seen       inflammatory drugs (NSAIDs) also associated with FD; epi-
  (eg, calcium-channel receptors); clinical data suggest starting        gastric pain alone not associated with psychologic symptoms
  medications at dose of 10 to 25 mg, titrating to 75 to 100 mg        Treatment: PPIs effective for acid peptic disorders; prokinet-
  as tolerated; doses typically below dose required for antide-          ics probably effective, but availability limited; not much evi-
  pressant effect; study showed 50% reduction in frequency of            dence for TCAs, but strong rationale seen; some evidence for
  CP episodes with imipramine compared to placebo                        efficacy of psychotherapy; no good evidence for Helico-
Selective serotonin reuptake inhibitors (SSRIs): sertraline              bacter pylori eradication; PPIs — empiric treatment indi-
  dose of 50 to 200 mg effective for severe pain, compared               cated as part of test-and-treat strategy; still indicated even if
  with placebo; citalopram in healthy volunteers found to de-            EGD negative, due to prevalence of reflux; may treat duode-
  crease pain perception                                                 nal hypersensitivity to acid; prokinetics — metoclopramide,
Serotonin-norepinephrine reuptake inhibitors (SNRIs): no                 cisapride (off market), domperidone (available only in Can-
  data on use for NCCP, but role possible based on use in func-          ada), and itopride effective, based on data; effective in subset
  tional abdominal pain and other neuropathic pain-mediated              of patients; worth trial in patient with poor response to other
  conditions                                                             drugs; speaker starts with metoclopramide (antinausea ef-
Others: trazodone — at dose of 100 to 150 mg, showed symptom-            fect); issue with black box warning and risk for tardive dys-
  atic improvement, compared to placebo; benzodiazepines —               kinesia (nil if used only for 1-2 mo); antidepressants —
  little data for use, but effective in short term if anxiety compo-     speaker uses low-dose TCAs (desipramine preferred because
  nent present or developed because of pain related to eating or         of lesser anticholinergic effects, unlike amitriptyline); small
  excessive concern about symptoms; gabapentin — similar to              study by speaker found amitriptyline effective; desipramine
  SNRIs; no clinical data in NCCP; possible role based on pain           effective in patients with functional bowel disorders (mostly
  modulatory effects in other conditions                                 IBS); venlafaxine (Effexor) ineffective; SSRIs worth trial if
Nonpharmacologic treatment: cognitive behavioral therapy                 symptoms severe; anxiolytic-antidepressant combination —
  (CBT) — effective; targeted at patient’s understanding of              study found combination of mood stabilizer and anxiolytic
  condition and learning different techniques to help manage             effective; due to role of anxiety as factor in FD;
  symptoms in acute setting and over time (gaining improve-              antispasmodics — found ineffective in clinical trials; effec-
  ment of symptoms); randomized controlled trial (RCT) of                tive in IBS; possibly useful in FD if given before meals in pa-
  CBT vs usual care found significantly improved pain severity           tients with significant postprandial symptoms; CBT —
  and frequency in CBT arm, with 50% of CBT patients pain-              effective based on longitudinal data (similar data for IBS);
  free at 1 yr; hypnosis — RCT found global improvement in               more effective than education; hypnotherapy — effective;
  symptoms in 80% of patients in hypnosis arm, compared to               diet — no specific elimination diet proven effective; low-fat
  23% in placebo arm                                                     diet prudent and possibly helpful; avoidance of NSAIDs
                                                                         helpful; individualize management
Functional Dyspepsia
Howard Mertz, MD, Clinical Assistant Professor of                      Narcotic Bowel Syndrome
Medicine, Vanderbilt University School of Medicine,                    Douglas A. Drossman, MD, Professor of Medicine and
Nashville, TN                                                          Psychiatry, University of North Carolina School of Medi-
Definition: Rome criteria — 1 symptom for 3 to 6 mo, in-
                                                                       cine, Chapel Hill
  cluding postprandial fullness, early satiety, epigastric pain,       Adverse effects of opioid on bowel: opioid bowel
  or epigastric burning (heartburn excluded); structural disease         dysfunction — slows bowel; includes constipation, nausea,
  (usually found on EGD) excluded                                        vomiting, gastroparesis, bloating, ileus, and sometimes pain;
Pathophysiology: hypersensitivity to distention and nutrients            narcotic bowel syndrome (NBS) — abdominal pain predomi-
  (similar to irritable bowel syndrome [IBS]); motility disorder         nant symptom; progressive and paradoxical increase in pain,
  (delayed gastric emptying and abnormal meal accommoda-                 leading to escalating doses of narcotics to relieve pain; un-
  tion); acid peptic disease, particularly reflux; 3 mechanisms          derrecognized
  overlap; gastric hypersensitivity — University of California         Typical clinical presentation: chronic or recurrent abdominal
  Los Angeles study using balloon dilation of stomach found              pain treated with narcotics; narcotics may relieve pain ini-
                                              AUDIO-DIGEST GASTROENTEROLOGY 24:03

  tially, but then tachyphylaxis occurs, requiring higher doses;                   narcotic dose wanes and improvement when narcotics rein-
  pain worsens when narcotic effect wears off; shorter pain-                       stituted (“soar and crash”); progression of frequency, dura-
  free periods result in increasing narcotic doses; increasing                     tion, and intensity of pain episodes; pain not explained by
  doses further alter motility and aggravate pain; occurs in pa-                   any other diagnosis
  tients with functional GI disorders (eg, IBS), organic dis-                    Narcotic withdrawal protocol: physician-patient relationship—
  ease, and in healthy subjects                                                    accept pain as real and give patient sense of hope; elicit patient’s
Prescription of narcotics in health care setting: prescribing                      concerns and expectations and address them; discuss effects of
  shifted from acute severe pain or palliative care of malignan-                   narcotics on pain and GI function; advise patient that he or she
  cies to prolonged use in chronic nonmalignant pain; pain                         will improve and not worsen when off narcotics and that other
  treatment centers shifted to narcotic treatments (“quick fix”)                   pain-control methods will be substituted while narcotics ta-
  over multidisciplinary pain treatment; no scientific evidence                    pered; use illustrations or graphics to present withdrawal pro-
  for long-term benefit of narcotics in nonmalignant pain;                         gram; involve responsible family member; assure that
  greater sensitivity of bowel in functional disorders, leading                    someone available to address patient’s issues; choice of clini-
  to more side effects from narcotics; enabled by third-party                      cal setting shifting to inpatient (faster, easier to handle compli-
  payers due to greater cost-benefit ratio                                         cations, and appropriate if monitoring required); outpatient
Physiology: high-dose opioids activate inhibitory receptors (in-                   detoxification performed in 6 to 8 wk (few days for inpatient);
  hibit pain, producing analgesia; mask excitatory receptors); as                  gauge patient’s willingness to go through program; address
  opioid given long-term and dose increased, tolerance develops                    challenging questions; SSRIs — not as beneficial (more anxio-
  in inhibitory receptors and excitatory receptors sensitized,                     lytic and antidepressant, rather than pain modulators); TCAs —
  paradoxically leading to hyperalgesia; glial cells —inflam-                       watch for side effects; duloxetine — marketed with pain as
  matory cells; found in dorsal horn of central nervous system;                    separate indication; indicated in peripheral neuropathy and fi-
  amplify pathologic pain; cause release of inflammatory cyto-                     bromyalgia; acts via central pain regulatory pathways; benzo-
  kines that enhance neuronal excitability; when used long-                        diazepine, eg, lorazepam (Ativan) and clonidine used to cover
  term, narcotics bind to glia via  receptors, causing release of                 during withdrawal period; tapering — should not taper fre-
  cytokines; opioids — also activate dynorphin release, produc-                    quency; maintain intervals but reduce dose; doses scheduled
  ing pain; long-term use activates glia via toll-like receptors                   (not prn); clonidine — blocks withdrawal effects; -2 adrener-
  (TLRs; “scavenger” receptors involved in inflammation and                        gic agonist; acts centrally to reduce anxiety and peripherally to
  infection); low-dose antagonists (eg, naloxone) block recep-                     reduce pain via bowel compliance; reduces diarrhea; prevents
  tors and enhance opioid analgesia                                                adrenergic effects of withdrawal; poor response seen in socio-
Diagnostic criteria: chronic or frequently recurring abdomi-                       pathic patients with history of drug-seeking behavior, and not
  nal pain treated with acute high-dose or long-term narcotics;                    committed to program
  pain worsens or incompletely resolves with continued or es-
  calating doses of narcotics; marked worsening of pain when

                        Suggested Reading                                        diac chest pain" adequate to exclude cardiac disease? Ann Emerg Med
                                                                                 44:565, 2004; Erratum in: Ann Emerg Med. 45:87, 2005; Pearson
Aro P et al: Anxiety is associated with uninvestigated and functional
                                                                                 RL: How effective are antidepressant medications in the treatment of
dyspepsia (Rome III criteria) in a Swedish population-based study.
                                                                                 irritable bowel syndrome and nonulcer dyspepsia? J Fam Pract
Gastroenterology 137:94, 2009; Fischler B et al: Heterogeneity of                49:396, 2000; Sandgren JE et al: Narcotic bowel syndrome treated
symptom pattern, psychosocial factors, and pathophysiological mech-              with clonidine. Resolution of abdominal pain and intestinal pseudo-
anisms in severe functional dyspepsia. Gastroenterology 124:903,                 obstruction. Ann Intern Med 101:331, 1984; Talley NJ et al: Func-
2003; Kusano M et al: Proton pump inhibitors improve acid-related                tional dyspepsia, delayed gastric emptying, and impaired quality of
dyspepsia in gastroesophageal reflux disease patients. Dig Dis Sci               life. Gut 55:933, 2006; Wong WM et al: Attitudes and referral pat-
52:1673, 2007; Longstreth GF: Functional dyspepsia–managing the                  terns of primary care physicians when evaluating subjects with non-
conundrum. N Engl J Med 354:791, 2006; Margo KL: Psychological                   cardiac chest pain--a national survey. Dig Dis Sci 50:656, 2005.
interventions for noncardiac chest pain. Am Fam Physician 72:1701,
2005; Miller CD et al: Is the initial diagnostic impression of "noncar-

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                                          AUDIO-DIGEST GASTROENTEROLOGY 24:03

                                              SOURCES OF GASTROINTESTINAL PAIN
                                     To test online, go to and sign in to online services.
                To submit a test form by mail or fax, complete Pretest section before listening and Posttest section after listening.
   1. Upper endoscopy is indicated in the presence of alarm symptoms on history and physical examination. These symptoms
        1.    Dysphagia
        2.    Odynophagia
        3.    Anemia
        4.    Weight loss
        5.    Gastrointestinal bleeding
             (A) 1,3,5                           (B) 2,4,5                         (C) 1,2,3,4                        (D) 1,2,3,4,5

   2. Proton pump inhibitors are used _______ in the management of noncardiac chest pain (NCCP).
             (A) Diagnostically
             (B) Therapeutically
             (C) Both diagnostically and therapeutically

   3. Which of the following drugs used to treat NCCP has a side effect of severe headache?
             (A) Nitrates                                                  (C) Botulinum toxin type A
             (B) Calcium channel blockers                                  (D) Tricyclic antidepressants (TCAs)

   4. The dose of TCAs used in the treatment of NCCP is _______ than the dose required for their antidepressant effect.
             (A) Higher                                                    (B) Lower

   5. Which of the following conditions is(are) associated with functional dyspepsia?
        1.    Anxiety
        2.    Depression
        3.    Postprandial distress
        4.    Epigastric pain
             (A) 1,3                             (B) 2,4                           (C) 1,2,3                          (D) 4

   6. There is good evidence that Helicobacter pylori eradication is effective in the treatment of functional dyspepsia.
             (A) True                                                      (B) False

   7. The following agents or strategies have been found effective for functional dyspepsia, except:
             (A) Combination of mood stabilizer and anxiolytic             (C) Antispasmodics
             (B) Cognitive behavioral therapy                              (D) Hypnotherapy

   8. Which of the following is the most predominant symptom of narcotic bowel syndrome (NBS)?
             (A) Abdominal pain                                            (C) Constipation
             (B) Bloating                                                  (D) Nausea and vomiting

   9. Long-term administration of opioids leads to development of tolerance in the _______ receptors and sensitization of the
      _______ receptors.
             (A) Inhibitory; excitatory
             (B) Excitatory; inhibitory

  10.   In tapering narcotics, there should be gradual reduction in the _______ rather than the _______.
             (A) Frequency of dosing; amount of drug administered
             (B) Amount of drug administered; frequency of dosing

Answers to Audio-Digest Gastroenterology Volume 24, Issue 02: 1-B, 2-D, 3-C, 4-C, 5-D, 6-A, 7-B, 8-A, 9-B, 10-B

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