GUT CHALLENGES
| GASTROPARESIS MANAGEMENT —Lawrence R. Schiller, MD, Program Director, Gastroenterology Fellowship,
Baylor University Medical Center, Dallas, TX
|
| Background: relatively rare (<10 000 new patients in United States annually)
|
 | Definition: symptomatic reduction in gastric emptying
|
| Symptoms: nausea, vomiting, dyspepsia (indigestion), weight loss, bloating, early satiety, and abdominal pain; any or
all may occur
|
| Causes: idiopathic (≈50% of cases); diabetes (comprises almost all remaining 50%); rarer causes include vagotomy,
Parkinson’s disease, vascular disease, and pseudoobstruction
|
| Idiopathic gastroparesis: possibly related to infection; may involve reprogramming or degeneration of enteric nervous
system; typically, symptoms persist after “garden-variety” gastroenteritis; some cases possibly related to autoimmune
disease (associated with neural degeneration or muscular fibrosis); early symptoms usually severe,
becoming milder over time; watchful waiting often reasonable approach
|
| Diabetic gastroparesis: usually associated with long-standing insulin-dependent diabetes; most patients have coexisting
neuropathy (older studies implicate vagal autonomic neuropathy); hyperglycemia delays gastic emptying;
keeping blood glucose (BG) to <200 mg/dL reduces symptoms; tight control of BG key part of management; hospitalization
and control of BG with glucose-insulin drip often provides adequate reduction in symptoms
|
| Postvagotomy gastroparesis: results mostly from altered proximal gastric accommodation due to surgery; impaired
antral peristalsis occurs with truncal vagotomy; planned vagotomy (seldom done) usually associated with drainage
procedure; incidental vagotomy—usually result of reflux surgery or bariatric procedures; due to inadvertent pressure-related
injury to vagus nerve; patients often complain of nausea; must be treated with drainage procedure; first
try paralyzing pylorus with botulinum toxin to see if symptoms improve (identifies best candidates for pyloroplasty)
|
| Gastric physiology: think of stomach as 2 organs in one
|
| Proximal stomach: reservoir; expands with food ingestion; contracts so increased intragastric pressure propels liquids
through
|
| Distal stomach: where peristalsis begins; grinds small particles and regulates gastric emptying of solids; particles
must be <1 mm to exit stomach; gastric smooth muscle contracts in response to cyclic electrical activity (gastric
peristalsis myogenic property of gastric smooth muscle; acts through direct electrical stimulation of interstitial
cells of Cajal, rather than neural activation, although nerves enhance amplitude of contraction)
|
| Regulators of gastric emptying: extrinsic and intrinsic nerves and postprandial hormone release; vagus and sympathetic
nerves mediate gastric sensations (eg, nausea, early satiety)
|
| Evaluation: history key; physical examination less important
|
| Diagnostic tests: endoscopy—to check for outflow obstruction; radiography—also checks for outflow obstruction
and looks further down gut; gastric emptying tests—often performed incorrectly, leading to inappropriate gastroenterology
referrals; electrogastrography—newer technique; use growing
|
| History: assess symptoms and their impact on patient; consider various gastrointestinal (GI) disorders, especially ones
associated with outlet obstruction (eg, peptic disease); look for systemic disease, including metabolic disorders (eg,
diabetes, hypothyroidism) or central nervous system (CNS) disorders; review patient’s medications (anticholinergic
agents or calcium channel blockers may affect gastric emptying); explore diet modification to determine what patient
can and cannot tolerate, and what may be exacerbating symptoms (eg, high-fat, high-fiber diet)
|
| Physical examination: assessment of nutritional status most important; check for succussion splash several hours
after patient eats; look for evidence of neuropathy or systemic disease; patients with significant gastroparesis often
have evidence of malnutrition, but patient may “eat around” gastroparesis and be obese
|
| Saline load test: developed in 1950s; instill 750 mL saline into stomach, wait 45 min, then siphon out remainder
with nasogastric tube; recovery of excessive volume evidence of slow emptying
|
| Radiopaque markers: never widely used
|
| Scintigraphy: current gold standard, although performance standards developed only recently; in new international
protocol, patient consumes low-volume, low-fat meal (eg, egg substitute and toast) labeled with technetium; nuclear
medicine physician then performs scintigraphy periodically for 4 hr to determine emptying curve; normal
result at 4 hr <10% retention; abnormal result defined as >10% retention at 4 hr and considered indication for
electrical stimulation; however, many community centers do studies at 1, 1.5, and 2 hr to maximize patient
turnover, and extrapolations of gastric emptying time may be inaccurate; take-home message for
gastroenterologists—ask nuclear medicine colleagues to follow international protocol of 4 hr; explain that it
involves only five 5-min imaging intervals per patient (total of 25 min machine time per patient)
|
| Electrogastrography: clinical value questionable, as no treatments yet exist that can change gastric electrical activity
|
Therapy
| Diet modification: stomach empties liquids more easily than solids; avoid hypertonic liquids (duodenum has osmotic
receptors that slow emptying when they detect hypertonicity); many over-the-counter meal supplements hypertonic,
and require dilution to be made isotonic (isotonic products available); patients should avoid sugary sodas
(high osmolality); minimize (but do not completely eliminate) fat, as it slows stomach emptying; fiber-rich foods
may be poorly tolerated unless disrupted first (eg, applesauce instead of whole apple); frequent small feedings usually
tolerated better than large meals
|
| Drugs: antiemetics—older agents reduce nausea by targeting brainstem; newer agents (5-HT3 antagonists) work well
but extremely expensive and affect gut 5-HT3 receptors, so efficacy may be impaired if gut receptors do not work
well; scopolamine skin patches may be better tolerated by some patients (however, anticholinergic properties may
reduce strength of gastric contractions); meclizine, dronabinol, or lorazepam effective in some
|
| Prokinetic drugs: often ineffective; metoclopramide—≈25% of patients develop intolerable side effects (prolonged
use associated with tardive dyskinesia); tegaserod—efficacy against gastroparesis not yet determined; studies suggest
effectiveness in upper GI tract requires larger dose than for constipation, and this may cause diarrhea;
erythromycin—intravenous (IV) administration effective in hospitalized patients; oral administration associated
with tachyphylaxis (for average-sized adult, 100 mg 15 min before meal sufficient for gastroparesis);
bethanechol—cholinergic agonist; good choice for postvagotomy gastric emptying problems; sildenafil—modest
effect on gastric emptying; intrapyloric botulinum toxin—some small studies suggest effectiveness, but transient
|
| Nutritional support: enteral feeding safer and better tolerated than total parenteral nutrition (TPN); jejunal feeding preferable
to gastric; direct jejunostomy preferable to gastrojejunostomy tube; patients with coexisting intestinal pseudo-obstruction
may require TPN (infection main risk)
|
| Surgery: gastrostomy tube to “vent” stomach may help control symptoms; jejunostomy may be performed simultaneously
to provide access for feeding
|
| Gastric electrical stimulation: works in ≈50% of patients; not quick fix; must be employed under compassionate
use protocol; device now in use administers high-frequency low-energy stimulation to stomach; thought to activate
nausea-regulating nerves in stomach (fairly good treatment for nausea, but little effect on stomach emptying); indicated
for chronic intractable nausea and vomiting secondary to gastroparesis of diabetic or idiopathic origin
|
| EVIDENCE-BASED ENTERAL AND PARENTERAL NUTRITION —Stephen A. McClave, MD, Professor of
Medicine, University of Louisville School of Medicine, Louisville, KY
|
| Importance of enteral feeding: 3 types of evidence
|
| Early vs delayed feeding: 15 randomized controlled trials and 2 meta-analyses; nutrition started within 36 hr of admission
to intensive care unit (ICU) cuts infection rate by 50%; reduces hospital length of stay (LOS) by 2 days
and mortality by up to 48%
|
| Enteral vs standard therapy (no nutritional therapy): >12 prospective randomized trials; according to recent meta-
analysis, aggressive enteral feeding starting one day after surgery reduces infection by 28% and LOS by one day,
compared to standard treatment; enteral feeding associated with lower incidence of anastomotic dehiscence
|
| Cumulative caloric balance: ≥5 studies; incidence of complications correlates with size of caloric deficit created during
first week of hospitalization by delay in inserting tube
|
| Role of gut in critical care: formerly viewed as passive organ; now known that not using gut during critical illness
associated with increased permeability; bacteria engage immune system, leading gut to become proinflammatory
organ; gut must be added to multiple organ failure syndrome (“if the gut goes down, it’s going to pull other organs
with it”); early establishment of enteral feeding in ICU can set tone for systemic immune system and attenuate oxidative
stress, with subsequent decreased risk for complications; after 3 to 4 days, ability to influence immune
changes declines
|
| Mechanisms: failure to use gut increases permeability; gut bacteria engage epithelial cells, leading to epithelial cell
death (apoptosis); occurs within hours, depending on disease severity; consequences of increased permeability
include increased risk for infection and organ failure; relation to lungs—cytokines released from mobilization of
macrophages or neutrophils travel through lymphatic channels to pulmonary capillaries (in animal studies, preserving
gut integrity lowers risk for adult respiratory distress syndrome [ARDS])
|
| Innate gut immune response: another consequence of gut disuse; bacteria or reduced blood flow and ischemia reperfusion
activate macrophages; primed neutrophils then go to other organs and may become activated by another
insult, eg, hypotension or hypoxemia; neutrophils can then enter lung via alveoli and wreak damage through oxidative
burst
|
| Acquired immune response: develops within 3 to 5 days; involves proliferation of dendritic macrophages in response to
bacterial overgrowth resulting from gut disuse; macrophages now release interleukin (IL)-12, which migrates down
lamina propria, where it encounters immature CD4 lymphocytes; in response to IL-12, CD4 cells proliferate according
to proinflammatory T-helper cell (TH )1 pathway, spilling over into systemic circulation; if patient fed, macrophages
release IL-4, causing lymphocytes to proceed down TH 2 pathway, which opposes TH 1 and elicits release of other, beneficial
cytokines that reduce inflammation; thus, end result of feeding is to mitigate immune response
|
| Promoting enteral feeding: at speaker’s institution, physicians usually prescribe only 65% of goal calories; patients
receive 80% of prescribed calories due to delivery problems; few patients achieve caloric goal within 3 days
(should be within 24-48 hr); feeding stops for 20% of infusion time, resulting in patients receiving only ≈50% of
goal calories, “barely in the ballpark of what’s needed to maintain gut integrity”
|
| What gastroenterologists can do: become proficient at deep jejunal access (1-2 loops below ligament of Treitz), and
learn how to secure it; assess gut tolerance firsthand; troubleshoot; manage complications quickly to prevent
worsening; facilitate delivery of enteral nutrition; support hospital’s nutrition team; some hospitals now training
dietitians in bedside postpyloric tube placement
|
| Tolerance: to determine which patients in ICU tolerating enteral feeding, evaluate stomach, small bowel, and colon;
nasgoastric tube output should be <1200 mL; gastroenterologist can help ICU staff select tube and level of GI tract
for tube placement; determine whether small bowel should be intubated and stomach decompressed simultaneously;
naloxone (Narcan) through feeding tube—2 amps in 10 mL saline q6h eliminates effects of opioid narcotics
on bowel (promotes contractility) without decreasing CNS effects of analgesia; minimize periods of ileus;
create, rather than wait for, bowel sounds; feeding ileus safe as long as tube in small bowel and patient not on pressor
agents; study—looked at naloxone vs placebo in patients on ventilator on fentanyl anesthesia; found use of
naloxone increased amount of enteral fluid patient absorbed, reduced overall gastric residual volume, and reduced incidence
of pneumonia from 56% to 34%; concluded that naloxone promotes tolerance; percutaneous endoscopic
gastrostomy (PEG) tubes—anticipate intolerance when placing; locate them down toward umbilicus, on patient’s
right side; shorter more perpendicular route than traditional and places tube in antrum; maintenance of gut
integrity—dose-dependent; requires at least 55% to 65% of caloric requirements (goal calories); trickle feeds of 10
to 20 mL/hr inadequate
|
| Immune-modulating formulas: in recent meta-analysis of 26 prospective randomized trials, incidence of infections
50% to 75% lower with immune-modulating compared to standard formulas; organ failure reduced 80%;
patients’ time on ventilator, in ICU, and in hospital reduced 1.5 to 3.5 days
|
| Prevent aspiration: reassess monitors; continue using glucose oxidase; increase residual volumes of patients on
ventilators; make sure feeding not stopped if volume high; up to 80% of patients show evidence of aspiration
at some point on ventilator, but pneumonia not inevitable (contributing factors include illness severity, comorbidities,
and volume of aspirate); to reduce risk for pneumonia and other nosocomial infections, clean patient’s
oropharynx twice daily with mouthwash (decreases risk for pneumonia up to 70%); remember that monitors
usually impede enteral feeding process; residual volume can be as high as 400 mL without increasing risk for
aspiration; placing tube in jejunum reduces risk for aspiration, but not necessarily for pneumonia
|
| Targeted physician education to promote enteral feeding: order formula or full liquids, rather than clear liquids; use
volume-based feeding; minimize time off feeding (feed through computed tomography if possible); commence
feeding first day after surgery; resume feeding early after diagnostic procedures; if patient goes on ventilator,
place tube and start feeding
|
Suggested Reading
Aring AM et al: Evaluation and prevention of diabetic neuropathy. Am Fam Physician 71:2123, 2005; Chapman MJ
et al: Gastrointestinal motility and prokinetics in the critically ill. Curr Opin Crit Care 13:187, 2007; Cynober L:
About immune-enhancing diets in critically ill patients. Crit Care Med 35:329, 2007; Galligan JJ, Vanner S: Basic and
clinical pharmacology of new motility promoting agents. Neurogastroenterol Motil 17:643, 2005; Jalilian E et al: Implantable
neural electrical stimulator for external control of gastrointestinal motility. Med Eng Phys 29:238, 2007; Jones
MP: Management of diabetic gastroparesis. Nutr Clin Pract 19:145, 2004; Koretz Rl et al: Does enteral nutrition affect
clinical outcome? A systematic review of the randomized trials. Am J Gastroenterol 102:412, 2007; Lobrano A et al:
Postinfectious gastroparesis related to autonomic failure: a case report. Neurogastroenterol Motil 18:162, 2006; Ochoa
JB, Caba D: Advances in surgical nutrition. Surg Clin North Am 86:1483, 2006; Parkman HP et al: American Gastroenterological
Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 127:1592,
2004; Pasha SF et al: Autoimmune gastrointestinal dysmotility treated successfully with pyridostigmine. Gastroenterology
131:1592, 2006; Syed AA et al: Current perspectives on the management of gastroparesis. J Postgrad Med 51:54,
2005; Tougas G et al: Standardization of a simplified scintigraphic methodology for the assessment of gastric emptying
in a multicenter setting. Am J Gastroenterol 95:78, 2000; Vittal H, Pasricha PF: Botulinum toxin for gastrointestinal
disorders: therapy and mechanisms. Neurotox Res 9:49, 2006; Wittek M, Williams MJ: New developments in treatment
for gastroparesis. Lippincotts Case Manag 10:313, 2005.
Educational Objectives
| The goal of this program is to improve the management of gastroparesis and update procedures and goals for adequate
enteral nutrition in severely ill patients. After hearing and assimilating this program, clinicians will be better
able to:
|
| 1. Name the primary regulators of gastric emptying.
|
| 2. Discuss the relative importance of history, physical examination, and diagnostic testing in the evaluation of
gastroparesis.
|
| 3. Explain why most prokinetic drugs are not recommended for the management of gastroparesis.
|
| 4. Describe the consequences of disrupted gut integrity.
|
| 5. Promote more aggressive parenteral nutrition at their institutions.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the following has been disclosed: Dr. McClave is a consultant
or speaker for Nestle, Ross, Novartis, Microvasive, Coram, and Nutrishare.
Acknowledgements
Drs. Schiller and McClave were recorded at the 31st Annual Texas Program, held September 15-17, 2006, in San Antonio,
and sponsored by the Texas Society for Gastroenterology and the American College of Gastroenterology. The
Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
|
