Lecture 21 Acute Diarrhea Moshenko

DEFINITION OF DIARRHEA:

• Relatively common disorder seen in practice

• ↑ frequency, fluidity, volume of fecal discharge

• ≥ 3 bowel movements/day

EPIDEMIOLOGY: rate of occurrence and severity differs in

developed & developing countries

DEVELOPED COUNTRIES:

Epidemi-ology

• No exact profile available

• Average of 1.4 episodes/year per person

Impact • Not usually fatal, but accounts for 6000 deaths/year in the US

• Results in considerable morbidity & substantial health care costs

Primary cause

• Infectious sources (bacteria, viruses, parasites)

DEVELOPING COUNTRIES:

Epidemi-ology

• Major problem

• Average 3 episodes/year in children < 3 yrs of age

Impact • In 2008: 1.3-1.9 million deaths/year in children < 5 years of age

• Death rates continually decreasing due to extensive distribution and use of oral rehydration solutions, increased breastfeeding, improved nutrition, better hygiene and sanitation

Primary cause

• Infectious sources (differing frequency profiles from developed countries)

• Poor nutrition status, poor sanitation & contaminated water/food supplies

PATHOPHYSIOLOGY:

NORMAL CONDITIONS (ADULTS):

• ~ 9L enters GIT daily from diet,

saliva, gastric juice, bile, pancreatic

juice & small intestine secretions

• Fluid reabsorbed prior to reaching

colon (500 mL left), then another

350 mL reabsorbed in colon

o Stool weighs 100-200 g (of

which 60-85% is water)

• Net water loss 50-100 mL/d in feces

NATURAL DEFENSE MECHANISMS IN GIT:

• Gastric acidity: prevents viable

pathogens from entering intestine

from stomach

• Peristaltic activity: propels pathogens

and their toxins along GIT

• GIT mucus: forms a protective barrier

• Mucosal tissue integrity

• Intestinal immunity: acquired with

repeated exposure to pathogens

DIARRHEA:

• Diarrhea occurs when absorptive capacity of small intestine is exceeded, and excess

fluid enters colon exceeding its absorptive capacity

• Diarrhea results from imbalance b/w fluid & electrolyte absorption/secretion in GIT

o These processes are regulated by solute movement (ions, AAs, monosacchs)

▪ Na is principal ion absorbed (active transport)

▪ Cl is principal ion secreted (active transport)

o Solute movement controlled by:

▪ Active & passive mechanisms/processes

• Active transport requires glucose (energy dependent)

▪ Hormonal control

o Water moves passively across gut wall following movement of various solutes

(Na+, K+, etc) to balance osmotic gradients

▪ Na is principal ion absorbed (active transport)

▪ Cl is principal ion secreted (active transport)

• With diarrhea, many ions are lost goal is to replace ions + water losses

ETIOLOGIC AGENTS/CAUSES: no specific etiology agent can be

determined/identified in 70-75% of cases

Dietary sources

• Green apples

• Excessive caffeine intake

• Spicy foods

• Sorbitol, mannitol, fructose (sweeteners)

Infection • Bacteria o Invasive = direct damage to GI mucosa

(Shigella, Salmonella) o Non-invasive = produce entero-toxins

which interfere with active ion transport mechanisms (ETEC, V. cholera)

• Viruses (norovirus, rotavirus, adenovirus, calicilviruses)

• Parasites (Giarda lamblia, Entamoeba histolytica,

Cryptosporidia) Drugs • Magnesium containing antacids

• Antibiotics (irritation, bacterial overgrowth, C. difficile, pseudomembranous colitis)

• Overuse of stimulant laxatives

• Anti-arrhythmics (digoxin, quinidine)

• Acid-reducing agents (H2RAs, PPIs)

• Narcotic/opioid withdrawal

• Anti-neoplastics

• Antiretrovirals

• Beta blockers

• Propranolol

• NSAIDs

• Alcohol

• Metoclopramide

• Domperidone

• Colchicine

• Furosemide

• Levothyroxine

• Metformin

• Misoprostol

• SSRIs

• Theophylline

Psych • Stress, anxiety = mild cases

Other • Malabsorption (ex// lactose intolerance)

• IBD (ulcerative colitis)

• Hyperthyroidism, diabetes, cirrhosis

• Carcinoma of intestinal tract

• Pyloric dumping syndrome following GI Sx

CLINICAL PRESENTATION AND HISTORY:

• Abrupt onset of frequent loose, watery stools, flatulence, malaise, abdominal pain/cramps

• Depending on etiology, vomiting, fever & muscle aches may be present as well

• Generally resolves within 72h, but may persist for up to 5-7 days (usually at ↓ frequency)

PATIENT ASSESSMENT (SCHOLAR):

Who? • Child, elder, debilitated, pregnant, chronic disease states = high-risk o ↑ risk dehydration, acid-base imbalances, morbidity & mortality

Sx (frequency & intensity)

• Fever? Blood/mucus in stool? Severe abdominal pain/cramping? N/V? Tenesmus? Weight loss? Signs of dehydration (thirst, tachycardia, decreased urination etc)?

Characteristic • Consistency (watery, runny, solid, etc)?

• Frequency of bowel movements (any changes)?

• Volume/quantity produced?

History • What has been done so far?

• Has this happened in the past?

Onset • When did it start? How long/duration? Abrupt/gradual onset?

• Any history of travel to high risk countries (recent, past months)?

• Flu? Any other people at home/work who are ill?

Aggravating factors

• What triggers it?

• Eaten anything differently (spicy food, milk products, coffee, alcohol)?

• New diet? Food poisoning? New medications/supplements/NHPs?

• Family history IBD, etc?

Remitting • What treatments have been tried?What helps?

REFERRAL:

Children (<3 years) Older children (>3 years) & adults

• Young (< 6 m) or weight < 18 lb (8.2 kg)

• Chronic or concurrent conditions

• Premature birth

• Fever ≥ 38.4o if < 3m, ≥ 39oC if 3-36 m

• Blood visible in stool

• High output diarrhea

• Persistent vomiting • S/S of dehydration (listlessness, dry mouth, ↓

tearing, sunken eyes, dry diaper, poor skin turgor, tachycardia, irritability, poor responsiveness, lightheadeddness, dizziness)

• Not drinking enough for rehydration

• Elderly individual

• Chronic or concurrent conditions

• Fever ≥ 39oC

• Blood in stool

• Presence of severe abdominal pain

• High output diarrhea; duration > 48 hrs

• Persistent vomiting

• Individual not drinking adequate (dry

mouth, ↓ tearing, excessive thirst, poor skin turgor, oliguria, orthostatic hypotension (light-headedness, dizziness), irritability, apathy, lethargy

• Not drinking enough for rehydration

Lecture 21 Acute Diarrhea Moshenko

PREVENTION:

Nursing homes, day care centers, etc • Isolation procedures to prevent spread of infectious agents

• Good hygiene

Food/dietary sources • Hidden dietary sources (ex// sorbitol in dietetic foods)?

• Milk allergy (lactase deficiency)?

• Food poisoning? Proper preparation & storage to reduce bacterial/viral contamination

Secondary to another illness • Identify and treat primary condition

Traveller’s diarrhea • Food and water precautions

• Prophylaxis in certain cases

SUPPORTIVE THERAPY/MEASURES = most important approach

• Goal: to control secondary effects of fluid and electrolyte loss and acid-base imbalance

o Consists of rapid rehydration (fluids & electrolytes) and re-feeding (introduction of solids)

o Oral rehydration therapy (ORT) now very common versus IV therapy (oral is as effective as IV therapy in mild-moderate cases of dehydration)

• Rationale:

o Fluids & electrolytes to replace losses

o Foods as energy sources for repair/regeneration of villous cells damaged or killed by pathogens/toxins

ADULTS: decrease activity until patient feels better or diarrhea resolves

1. First 24 hours (or until diarrhea and/or vomiting lessens or stops)

• 2-3 L of clear fluids per day (broth-based soups, fruit juices (not fruit drinks = high glucose)), sports drinks in reasonable amounts); gelatin

• Oral rehydration fluids (ex// Gastrolyte, etc)

2. Next 24 hours (or earlier, if frequency ↓ or individual has been rehydrated)

• Introduce foods as tolerated (slowly at first), but ASAP after rehydration (typically shortens course of diarrhea)

o Complex carbs (cooked rice, potatoes, cereals (rice, grain), bread, crackers)

o Cooked fruits & vegetables; lean meats; cooked eggs

o Yogurt (source of lactobacillus = probiotic) – NOTE: some individuals may have temporary lactose intolerance as consequence of diarrhea

• Avoid: fatty foods, high in simple sugars (including tea, soft drinks, excess sports drinks), spicy or other irritating foods (ex// coffee)

3. Progress to normal diet over next 2-3 days (or longer if some degree of diarrhea present)

INFANTS AND CHILDREN:

• Most cases can be handled in same way as adults, IF diarrhea has been present for < 24 hours and there are no signs of dehydration and/or fever

► If signs of dehydration initial rapid oral rehydration over 4-6 hour period, then proceed to maintenance rehydration therapy

► If no dehydration proceed directly to maintenance therapy guidelines

• Refeeding: integral component of optimal oral therapy regimens; best foods for feeding = as listed previously for adults, but age appropriate

► Children who have diarrhea but are not dehydrated continue to feed age-appropriate diets

► Children who require rehydration feed age-appropriate diets as soon as they have been rehydrated

o Unrestricted diets do not worsen course of symptoms of mild diarrhea and can ↓ stool output compared with ORT and IV treatment alone

o Breast-feeding infants can be nursed safely during episodes of diarrhea allows for faster recovery

o Full-strength animal milk or animal milk formula is usually well-tolerated in cases of mild, self-limited diarrhea (in > 80% of children)

o Weaned children: combinations of milk + cereal are appropriate and well-tolerated

o Monitor for signs of milk malabsorption (re: possible, temporary lactase deficiency): foamy stools or ↑ stool frequency once again

GENERAL GUIDELINES FOR CHILD WITH CLINICAL SIGNS OF DEHYDRATION:

1. Initial rehydration: oral rehydration solution with sodium content of 50-90 mEq/L (Pedialyte, Gastrolyte); offered to child ad libitum (small frequent

amounts as spoonfuls or small sips, small volumes in bottles for infants)

MILD DEHYDRATION • Sx: ↑ thirst & oliguria; slightly dry lips; thick saliva

• Txt: 50 mL/kg of oral rehydration solution over 4-8 hr

MOD DEHYDRATION • Sx: marked thirst & oliguria; diminished/absent tears; dry lips & buccal mucosa; ↓ skin turgor; listlessness

• Txt: 100 mL/kg of oral rehydration solution over 4-6 hr

SEVERE DEHYDRATION (typically hospitalized)

• Child with signs of shock must be given IV Ringer’s Lactate or Normal Saline in boluses of 40 mL/kg until normal circulatory status is restored

• ORT should then be initiated

2. Maintenance therapy: use an oral rehydration with a lower sodium content (40-60 mEq/L); give a minimum of 150 mL/kg/day of total fluids

• If solution with high sodium content is used (50-90 mEq/L) then alternate with liquids that have low solute content (water, formula)

• Ongoing stool losses = replace fluids on one-to-one basis with 10 mL/kg of body weight, or 125-250 mL solution for each diarrheal stool

NOTE: oral rehydration solutions (ex// Gastrolyte Powder, Pedialyte Liquid)

• Contain a balance of Na+, K+, Cl-, bicarbonate, citrate, glucose/dextrose

• Often taste quite salty children may therefore not want to drink them willingly

o Start with small amounts frequently at first (every few minutes) as child may adapt to taste

o Freeze solution into “popsicles” (commercially available – ex// Pedialyte Popsicles) will often make ORT solution more acceptable/palatable

Lecture 21 Acute Diarrhea Moshenko

SPECIFIC THERAPY WITH ANTIBIOTICS:

• Used in selected cases – high fever, bloody stools

o Based on identification of pathogen (bacteria C&S)

o Often diarrheal episode has resolved before C&S results are back

• Clinical trials with antibiotics: generally, do not shorten course of diarrhea

o Antibiotics can also cause diarrhea: pseudomembranous colitis, direct irritation (ex// titration, erythromycin)

SYMPTOMATIC THERAPY:

• Non-prescription drugs: common; generally recommended only for acute self-limiting diarrheas

o US FDA study: only 3 compounding/drugs recommended therapeutically effective: attapulgite, loperamide, polycarbophil

o None of these agents/products should be used for > 2 days without medical supervision

▪ Generally not recommended for children < 2 years

▪ Use cautiously in elderly or debilitated patient

▪ Important to emphasize use of ORT and re-feeding

• Goal: to stop/reduce severity of diarrhea by ↓ frequency, or ↑ consistency of bowel movements

• Note: none of these agents/products should be used for > 2 days without medical supervision

OTC Medication MOA Dose Other notes

Attapulgite, Activated Kaopectate: 600 mg/tablet, 300 mg/chewable tablet; 600 mg/15 mL suspension Also Fowlers

• Adsorbent o Attapulgite =

clay-based o Polycarbophil =

modified cellulose

• Absorbs large amounts of water = = ↑ stool consistency

• May also bind bacterial toxins

• Adults: 1200 mg initially, then 1200 -1500 mg after each BM to a max of 8400 mg/day

• Children (6-12 years): ½ adult dose

• Children (3-6 years): ¼ adult dose

• No significant SEs

• Can use in both adults & children

• Do not use more than 2 days without medical supervision

• Less effective than loperamide

• Should be taken 2 hrs apart from other meds Polycarbophil Prodiem Bulk Fiber Therapy

• Adults: 1 g PO QID or PRN (max 6 g/day)

• Children (6-12 years): 0.5 g PO TID or PRN (max 3 g/day)

• Children (3-6 years): 0.5 g PO BID (max 1.5 g/day)

Loperamide Imodium: 2 mg/capsule or caplet; 0.13 mg/mL liquid; Also available as Imodium Quick Dissolve

• Antimotility agent

• Synthetic opioid analog

• Acts on intestinal µ-opioid receptor to decrease ACh release ↓ GIT motility more time for fluid reabsorption

• ↑ consistency, ↓ frequency of stools

• Adults: 4 mg initially, then 2 mg after each loose BM (max 16 mg/day)

• Children (6-8 years): 2 mg PO up to BID (max 4 mg/day)

• Children (8-12 years): 2 mg PO up to TID (max 6 mg/day)

• SE: abdominal cramps/discomfort, drowsiness, dry mouth, skin rash, constipation

• May worsen diarrhea in some cases (toxins: ↑ contact time more tissue damage)

• Do not recommend if patient has fever (>38.5) or bloody stools

• Contraindicated in children < 2 years (some references < 6 yrs): ↑ incidence CNS depression

• Caution in < 12 years old

Diphenoxylate-atropine Lomotil 2.5 mg diphenoxylate and 0.025 mg atropine/tablet

• Adults: 5 mg initially, followed by 2.5 mg after each loose BM to a max of 20 mg/day

• Children > 4 years: 0.3-0.4 mg/kg daily in divided doses

• SE: nausea, drowsiness, dizziness, blurred vision, constipation

• May worsen diarrhea in some cases (toxins: ↑ contact time more tissue damage)

• Do not recommend if pthas fever, bloody stools

• Do not use in children < 4 years; use with extreme caution in children o CNS depression SEs o Atropine: restlessness, excitement, etc

• Should not be used in pregnancy & breastfeeding

Bismuth subsalicylate Pepto-Bismol

• Stimulates absorption of fluid/electrolytes across intestinal wall

• Anti-inflammatory

• Binds bacterial toxins

• Children > 14 years & adults: 525 mg q30-60 min PO PRN (max 4.2 g/day)

• Not as effective as other meds for acute diarrhea

• May interact with tetracycline, doxy, quinolones, anticoagulants, probenecid, methotrexate

• Contraindications: allergy to salicylates, renal insufficiency, gout, GI bleed

• May blacken tongue/stool, tinnitus

• Not recommended for children < 12 yr (Reye’s)

• Do not use in pregnancy

Probiotics Lactobacillus acidophilus with bifidus (Webber, Jamieson) Bifidobacterial saccharomyces boulardii (yeast, Florastor)

• Restores natural microflora in intestine

• Used for both prevention and treatment of diarrhea