case study on diarrhoea in child ppt

DIARRHEA IN CHILDREN

Sep 04, 2014

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DIARRHEA IN CHILDREN. Maria Naval C. Rivas Department of Pediatrics The Medical City. SOURCES. Nelson’s Textbook of Pediatrics 18 th edition World Health Organization: A Manual for Physicians and Other Senior Health Workers, 2005. DEFINITION.

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DIARRHEA IN CHILDREN Maria Naval C. Rivas Department of Pediatrics The Medical City

SOURCES • Nelson’s Textbook of Pediatrics 18th edition • World Health Organization: A Manual for Physicians and Other Senior Health Workers, 2005

DEFINITION • passage of unusually loose or watery stools • at least 3 times in a 24 hour period • Acute diarrhea: < 2 weeks • Chronic diarrhea: > 2 weeks

EPIDEMIOLOGY • 2nd leading cause of morbidity • 1,135 cases per 100,000 population • 6th leading cause of mortality • 5.3 deaths per 100,000 population • 1000M episodes of diarrhea/year in children <5y • 5M deaths in <5y • 80% deaths in 1st 2y of life (1/3 of all deaths) Sources: Carlos M.D., C. & Saniel M.D., M. Etiology and Epidemiology of Diarrhea. Research Institute for Tropical Medicine : Philippine Health Statistics, 2000

APPROACH TO A CHILD WITH ACUTE DIARRHEA Main Objectives 1. assess degree of dehydration and provide fluid and electrolyte replacement 2. prevent spread of enteropathogen 3. in select episodes, determine etiologic agent and provide specific therapy if indicated

APPROACH TO A CHILD WITH ACUTE DIARRHEA Pertinent Data oral intake frequency of stools volume of stools presence of blood or mucus in stool general appearance & activity of child frequency of urination

APPROACH TO A CHILD WITH ACUTE DIARRHEA others: day care attendance recent travel to a diarrhea endemic area use of antibiotics exposure to contacts with similar symptoms intake of seafood, uncooked meat, unpasteurized milk, unwashed vegetables, contaminated water systemic sx: fever, vomiting, seizure

APPROACH TO A CHILD WITH ACUTE DIARRHEA Degree of Dehydration MILD DEHYDRATION (3-5%) - normal or increased pulse, decreased urine output, thirsty, normal physical examination MODERATE DEHYDRATION (7-10%) - tachycardia, little or no urine output, irritable/ lethargic, dry mucous membranes, mild tenting of skin, delayed capillary refill, cool and pale

APPROACH TO A CHILD WITH ACUTE DIARRHEA Degree of Dehydration SEVERE DEHYDRATION (10-15%) - rapid and weak pulse, decreased blood pressure, no urine output, very sunken eyes and fontanel, no tears, dry mucous membranes tenting of the skin, very delayed capillary refill, cold and mottled

ASSESSMENT OF DIARRHEA PATIENTS FOR DEHYDRATION

APPROACH TO A CHILD WITH ACUTE DIARRHEA Treatment Plan A - home therapy to prevent dehydration and malnutrition • Give the child more fluids than usual • ORS solution • salted drinks (e.g. salted water, salted yoghurt drink) • vegetable or chicken soup with salt • Give supplemental zinc (10-20mg) for 10-14 days • Continue to feed the child

APPROACH TO A CHILD WITH ACUTE DIARRHEA • Take child back to health worker if there are signs of dehydration or other problems • starts to pass many stools • repeated vomiting • becomes very thirsty • eating or drinking poorly • develops a fever • has blood in the stool • child does not get better in 3 days

APPROACH TO A CHILD WITH ACUTE DIARRHEA Treatment Plan B • oral rehydration therapy with ORS in a health facility • monitoring progress of oral rehydration • supplemental zinc (10-20mg) for 10-14 days • food should not be given during initial 4-hour rehydration period • breastmilk may be given continuously

Treatment Plan B: Approximate amount of ORS to give in the initial 4 hours

APPROACH TO A CHILD WITH ACUTE DIARRHEA Reduced osmalarity ORS mmol/liter Sodium 75 Chloride 65 Glucose 75 Potassium 20 Citrate 10 TOTAL OSMOLARITY 245

APPROACH TO A CHILD WITH ACUTE DIARRHEA Treatment Plan C • rapid intravenous rehydration • may give oral ORS if child can already drink - usually after 1-4 hours • monitoring progress of IV hydration • if IV therapy not available, give ORS by NGT at 20cc/kg/hr x 6 hrs. • manage electrolyte disturbance

IV Treatment of Children & Adults with Severe Dehydration

IV Treatment of Children & Adults with Severe Dehydration 1. Restore intravascular volume • normal saline: 20ml/kg over 20 mins • repeat until intravascular volume is restored 2. Calculate 24-hr water needs • calculate maintenance water • 0-10kg 100ml/kg • 11-20kg 1000ml + 50ml/kg for each kg > 10kg • > 20kg 1500ml + 20ml/kg for each kg > 20kg • calculate deficit water • Percent dehydration x weight

IV Treatment of Children & Adults with Severe Dehydration 3. Calculate 24-hour electrolyte needs • calculate maintenance sodium and potassium • calculate deficit sodium and potassium • Na deficit = water deficit x 80 mEq/L • K deficit = water deficit x 30 mEq/L 4. Select an appropriate fluid • nornal saline or Ringer lactate 5. Replace any ongoing losses as they occur

APPROACH TO A CHILD WITH ACUTE DIARRHEA Electrolyte Disturbances • Hypernatremic Dehydration (serum Na > 150 mmol/L) - due to drinks with excessive sugar or salt - e.g. soft drinks, commercial fruit drinks, concentrated infant formula - s/sx: extreme thirst convulsions

APPROACH TO A CHILD WITH ACUTE DIARRHEA Electrolyte Disturbances • Hyponatremic Dehydration (serum Na < 130 mmol/L) - due to drinking mostly water or drinks with little salt - common in Shigellosis and in severe malnutrition with edema - s/sx: lethargy

APPROACH TO A CHILD WITH ACUTE DIARRHEA Electrolyte Disturbances • Hypokalemia (serum K+ < 3 mmol/L) - s/sx: muscle weakness, paralytic ileus, cardiac arrhythmia, impaired kidney function

CLINICAL TYPES OF DIARRHEA • Acute Watery Diarrhea • Acute Bloody Diarrhea • Persistent Diarrhea

ACUTE WATERY DIARRHEA Viruses Rotavirus Astrovirus Adenovirus Calcivirus ( e.g. Norwalk agent )

ACUTE WATERY DIARRHEA Pathogenesis - destroy villus tip cells in the SI • imbalance in ratio of intestinal absorption and secretion • malabsorption of complex carbohydrates, sp. lactose - gastric mucosa is not affected - greatly enhances intestinal permeability to macromolecules increase risk of food allergies

ACUTE WATERY DIARRHEA Pathogenesis - increased vulnerability of infants • decreased intestinal reserve function • lack of specific immunity • decreased non-specific host defense mechanisms (e.g. gastric acid, mucus)

ACUTE WATERY DIARRHEA Rotavirus - most common viral cause; RNA virus - > 125 M of cases / yr in < 5 y/o - 600,000 deaths per year - most severe in ages 3mos – 24mos - transmission: fecal-oral route days before and after the clinical illness

Rotavirus in the Philippines - based on 2005 data of PPS - most common viral cause - 3,700 deaths from total of 14,500 deaths related to childhood diarrhea - most severe in ages 3mos – 24mos - 65% of diarrhea-related hospital admissions

Clinical Manifestations incubation: < 48 hours mild to moderate vomiting & fever onset of frequent, watery diarrhea Complications: dehydration, severe and prolonged symptoms in malnourished and immunocompromised children

Diagnosis - clinical and epidemiological features - enzyme immunoassays : 90% specificity/ sensitivity - stool exam : free of blood and leukocytes Treatment - rehydration - probiotics (Lactobacillus species) , zinc - no role for antiviral nor antibacterial drugs - no role for antiemetics nor antidiarrheal drugs

Prognosis - after initial infection, 38% protection against subsequent infection 77% against diarrhea 87% against severe diarrhea Prevention - good hygiene and isolation - breastfeeding - vaccine: > 80% protection against severe disease

Differential Diagnosis 1. Astrovirus – RNA virus - milder with less significant dehydration 2. Norwalk virus – RNA virus - short incubation period (<12 hrs) - vomiting and nausea tend to predominate - clinical picture resembles “food poisoning” by S. aureus

Differential Diagnosis 3. Adenovirus – DNA virus - 5-9% of diarrhea in children - mainly a respiratory virus that grows well in the epithelium of SI - diarrhea is watery but of longer duration ( 10-14 days )

Differential Diagnosis 3. Adenovirus - may be assoc with conjunctivitis, myocarditis, hemorrhagic cystitis, intussusception, encephalomyelitis - transmission: respiratory fecal-oral routes - diagnosis: virus detection by culture or PCR increase in antibody titers

ACUTE WATERY DIARRHEA Enterotoxigenic Escherichia coli (ETEC) - major cause of infantile diarrhea - important etiologic agent of traveler’s diarrhea - 20-30% of diarrhea worldwide and in the Philippines

Pathogenesis - colonization of SI and subsequent elaboration of enterotoxins - enterotoxins: heat-labile (LT) heat- stable (ST) - require a large inoculum of organisms to induce disease - mode of transmission: food or water-borne

ACUTE WATERY DIARRHEA Enteropathogenic Escherichia coli (EPEC) - major cause of infant diarrhea and mortality in < 2 years - pathogenesis: “attaching and effacing lesion” • intimate attachment of bacteria to epithelial surface and effacement of host cell microvilli

Clinical Manifestations - explosive, watery, non-bloody, non-mucoid - abdominal pain - nausea and vomiting - +/- fever - self-limited: 3-5 days but occassionally > 1week

Diagnosis - clinical features seldom distinctive - laboratory studies not readily available: • isolation of bacteria from stool cultures • biochemical criteria (fermentation patterns) • tissue culture • identification of specific virulence factors • detection of antibodies

Treatment - rehydration - early refeeding - history of travel from developing country - DOC: Trimethoprim-Sulfamethoxazole Prevention - prolonged breastfeeding - personal hygiene - proper food and water handling - public health measures

ACUTE WATERY DIARRHEA CHOLERA (Vibrio cholerae) - 5-7M cases and > 100,000 deaths/yr. - an EMERGENCY!! - latest epidemic in 1990s in Americas death rate = 12,000 deaths/70,000 cases -V. cholerae is a gram-negative rod with a polar, flagellum - 2 strains: O1 and O139

Pathogenesis colonization of SI by > 10 viable vibrios production of cholera toxin (CT) entry of toxin into intestinal epithelial cells high cAMP level decrease absorption of Na and Cl by villous cells active secretion of Cl by crypt cells 8

Clinical Manifestations - most are asymptomatic - ¼ with mild to moderate disease - 2-5% with severe disease - hallmark: massive loss of fluids and electrolytes - incubation: 6 hours – 5 days - watery diarrhea, vomiting, low-grade fever - severe: profuse, painless, watery diarrhea with rice-water consistency and fishy odor

Diagnosis - primarily clinical - laboratory confirmation during epidemics • culture by thiosulfate-citrate-bile-sucrose(GOLD STANDARD) • appear as large, yellow colonies against bluish-green medium • culture by tellurite-taurocholate-gelatin agar • small, opaque colonies with zone of cloudiness around them

Treatment - fluid and electrolyte replacement - refeeding does not affect purging rates or duration of illness - success of ORT shown in Peru epidemic in 1991 with <1% mortality - antibiotics for moderate or severe disease DOC: tetracycline and doxycycline resistant strains: TMP-SMZ, Erythromycin, Furazolidone

Complications - dehydration: hypoglycemia acute tubular necrosis - hypokalemia: cardiac arrhythmia paralytic ileus - sodium disturbance: lethargy seizures coma

Prevention - prolonged breastfeeding - safe food and water handling - improved vaccine is priority - Cholera vaccine • 50% efficacy, highly reactogenic, does not protect against O139 vibrios • used only for very high-risk persons (e.g. achlorhydria) with high probability of exposure • not recommended for < 6 mos old

ACUTE WATERY DIARRHEA Staphylococcus aureus - most common cause of food poisoning - ingestion of pre-formed enterotoxins sudden, severe vomiting watery diarrhea - treatment: supportive - prevention: • eat/refrigerate prepared food immediately • exclude those with Staphylococcal skin infections from food handling or preparations 2-7 hours

ACUTE WATERY DIARRHEA GIARDIASIS (Giardia lamblia) - frequently identified during outbreaks assoc with drinking water - high prevalence during childhood - role of child-care centers - transmission: water and food borne low infectious dose extended periods of cyst shedding resistant to chlorination and UV light irradiation

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A Case Report of Severe Dehydration and Complications in a 10 Month Old Baby Girl Presenting with Acute Diarrhoea in a Resource-Limited Hospital Setting

Article sidebar, main article content.

Introduction : Diarrhoea continues to pose a significant threat to child health, often resulting in severe complications such as hypovolemic shock, electrolyte imbalances, and metabolic acidosis, which can lead to morbidity and mortality. This case study aims to illustrate the management of diarrhoea in a resource-constrained hospital setting.

A 10 Month old Baby Girl presented with symptoms including frequent watery stools (10 times/day), vomiting (3 times/day), and fever. The child exhibited signs of dehydration, weakness, refusal to drink, rapid and labored breathing, and loss of consciousness. Physical examination revealed a high heart rate (165 beats per minute), impalpable peripheral pulse, elevated respiratory rate (44 breaths per minute), normal oxygen saturation (98%), and slight hypothermia (36.7°C). Additionally, the child displayed clinical signs of dehydration such as sunken eyes, reduced tear production, diminished bowel sounds, delayed skin turgor, and prolonged capillary refill time.

Laboratory investigations showed leukocytosis (23,600/μl), hyponatremia (127 mmol/l), and hypokalemia (2.66 mmol/l). Treatment commenced with rapid fluid resuscitation using Ringer lactate at 20 ml/kg BW over 20 minutes, followed by 30 ml/kg BW over the next 30 minutes, and finally 70 ml/kg BW over 2 hours and 30 minutes. Subsequently, the patient received D5% 500 cc with sodium bicarbonate and KCL 7.4% within 24 hours. Oxygen therapy, antibiotics, probiotics, and zinc supplementation were also administered.

Article Details

Diarrhea in Children

• Pathophysiology |
• Evaluation |
• Treatment |
• Key Points |

Diarrhea is frequent loose or watery bowel movements that deviate from a child’s normal pattern.

Diarrhea may be accompanied by anorexia, vomiting, acute weight loss, abdominal pain, fever, or passage of blood. If diarrhea is severe or prolonged, dehydration is likely. Even in the absence of dehydration, chronic diarrhea usually results in weight loss or failure to gain weight.

Diarrhea is a very common pediatric concern, and diarrhea and dehydration cause about 1.5 to 2.5 million deaths/year worldwide. It accounts for about 9% of hospitalizations in the US among children < 5 years of age.

Diarrhea in adults is discussed elsewhere.

Pathophysiology of Diarrhea in Children

Mechanisms of diarrhea may include the following:

Inflammatory

Malabsorptive

Osmotic diarrhea results from the presence of nonabsorbable solutes in the gastrointestinal tract, as with lactose intolerance . Fasting for 2 to 3 days stops osmotic diarrhea.

Secretory diarrhea results from substances (eg, bacterial toxins) that increase secretion of chloride ions and water into the intestinal lumen. Secretory diarrhea does not stop with fasting.

Inflammatory diarrhea is associated with conditions that cause inflammation or ulceration of the intestinal mucosa (eg, Crohn disease , ulcerative colitis ). The resultant outpouring of plasma, serum proteins, blood, and mucus increases fecal bulk and fluid content.

Malabsorption may result from osmotic or secretory mechanisms or conditions that lead to less surface area in the bowel. Conditions such as pancreatic insufficiency and short bowel syndrome and conditions that speed up transit time cause diarrhea due to decreased absorption.

Etiology of Diarrhea in Children

The causes and significance of diarrhea ( see Table: Some Causes of Diarrhea ) differ depending on whether it is acute ( < 2 weeks) or chronic ( > 2 weeks). Most cases of diarrhea are acute.

Acute diarrhea usually is caused by

Gastroenteritis

Antibiotic use

Food allergies

Food poisoning

Most gastroenteritis is caused by a virus; however, any enteric pathogen can cause acute diarrhea.

Chronic diarrhea usually is caused by

Dietary factors

Celiac disease

Inflammatory bowel disease

Chronic diarrhea can also be caused by anatomic disorders and disorders that interfere with absorption or digestion.

Some Causes of Diarrhea

Evaluation of Diarrhea in Children

History of present illness

Review of systems should seek symptoms of both complications and causes of diarrhea. Symptoms of complications include weight loss and decreased frequency of urination and fluid intake (dehydration). Symptoms of causes include urticarial rash associated with food intake (food allergy); nasal polyps, sinusitis, and poor growth (cystic fibrosis); and arthritis, skin lesions, and anal fissures (inflammatory bowel disease).

Past medical history should assess known causative disorders (eg, immunocompromise, cystic fibrosis, celiac disease, inflammatory bowel disease) in the patient and family members.

Physical examination

Vital signs should be reviewed for indications of dehydration (eg, tachycardia, hypotension) and fever.

General assessment includes checking for signs of lethargy or distress. Growth parameters should be noted.

Because the abdominal examination may elicit discomfort, it is advisable to begin the examination with the head. Examination should focus on the mucous membranes to assess whether they are moist or dry. Nasal polyps; psoriasiform dermatitis around the eyes, nose, and mouth; and oral ulcerations should be noted.

Examination of the extremities focuses on skin turgor, capillary refill time, and the presence of petechiae, purpura, other skin lesions (eg, erythema nodosum, pyoderma gangrenosum), rashes, and erythematous, swollen joints.

Abdominal examination focuses on distention, tenderness, and quality of bowel sounds (eg, high-pitched, normal, absent). Examination of the genitals focuses on presence of rashes and signs of anal fissures or ulcerative lesions.

The following findings are of particular concern:

Tachycardia, hypotension, and lethargy (significant dehydration )

Bloody stools

Bilious vomiting

Extreme abdominal tenderness and/or distention

Petechiae and/or pallor

Interpretation of findings

Antibiotic-related, postinfectious, and anatomic-related causes of diarrhea are typically clear from the history. Determination of the time frame helps establish whether diarrhea is acute or chronic. Establishing the level of acuity is also important. Most cases of acute diarrhea have a viral etiology, are low acuity, and cause fever and nonbloody diarrhea. However, bacterial diarrhea can lead to serious consequences; manifestations include fever, bloody diarrhea, and possibly a petechial or purpuric rash.

Symptoms associated with chronic diarrhea can vary and those of different conditions can overlap. For example, Crohn disease and celiac disease can cause oral ulcerations, a number of conditions can cause rashes, and any condition can lead to a poor growth pattern. If the cause is unclear, further tests are done based on clinical findings ( see Table: Some Causes of Diarrhea ).

Testing is unnecessary in most cases of acute self-limited diarrhea. However, if the evaluation suggests an etiology other than viral gastroenteritis, testing should be directed by the suspected etiology ( see Table: Some Causes of Diarrhea ).

Treatment of Diarrhea in Children

Specific causes of diarrhea are treated (eg, gluten-free diet for children with celiac disease).

General treatment focuses on hydration, which can usually be done orally. IV hydration is rarely essential. (CAUTION: Antidiarrheal drugs

Rehydration

Oral rehydration solution (ORS) should contain complex carbohydrate or 2% glucose and 50 to 90 mEq/L (50 to 90 mmol/L) sodium. Sports drinks, sodas, juices, and similar drinks do not meet these criteria and should not be used. They generally have too little sodium and too much carbohydrate to take advantage of sodium/glucose cotransport, and the osmotic effect of the excess carbohydrate may result in additional fluid loss.

ORS is recommended by the World Health Organization and is widely available in the US without a prescription. Premixed solutions are also available at most pharmacies and supermarkets.

If the child is also vomiting, small, frequent amounts are used, starting with 5 mL every 5 minutes and increasing gradually as tolerated ( see Oral Rehydration ). If the child is not vomiting, the initial amount is not restricted. In either case, generally 50 mL/kg is given over 4 hours for mild dehydration, and 100 mL/kg is given over 4 hours for moderate dehydration. For each diarrheal stool, an additional 10 mL/kg (up to 240 mL) is given. After 4 hours, the patient is reassessed. If signs of dehydration persist, the same volume is repeated.

Diet and nutrition

Children with an acute diarrheal illness should eat an age-appropriate diet as soon as they have been rehydrated and are not vomiting. Infants may resume breast milk or formula.

For chronic nonspecific diarrhea of childhood (toddler's diarrhea), dietary fat and fiber should be increased, and fluid intake (especially fruit juices) should be decreased.

For other causes of chronic diarrhea, adequate nutrition must be maintained, particularly of fat-soluble vitamins.

Diarrhea is a common pediatric concern.

Gastroenteritis is the most common cause.

Testing is rarely necessary in children with acute diarrheal illnesses.

Dehydration is likely if diarrhea is severe or prolonged.

Oral rehydration is effective in most cases.

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Evaluating the Patient With Diarrhea: A Case-Based Approach

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The evaluation of the patient with diarrhea can be complex and the treatment challenging. In this article, the definition of diarrhea and the pathophysiologic mechanisms that lead to diarrhea are reviewed. A simplified 5-step approach to the patient with diarrhea is provided and applied in a case-oriented manner applicable to everyday clinical practice. On completion of this article, you should be able to (1) define diarrhea, (2) outline various pathophysiologic mechanisms of diarrhea, and (3) describe a simplified 5-step approach to facilitate the evaluation of diarrhea.

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Learning Objectives: Educational objectives. On completion of this article, you should be able to (1) define diarrhea; (2) outline various pathophysiologic mechanisms of diarrhea; and (3) describe a simplified 5-step approach to facilitate the evaluation of diarrhea.

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Diarrhea can be defined by increased stool frequency, liquidity, or volume. Health care professionals typically think of diarrhea as an increase in stool frequency 1 ; however, for most individuals, the essential characteristic of diarrhea is the passage of loose stools. 2 Diarrhea is objectively defined as passing a stool weight or volume greater than 200 g or 200 mL per 24 hours. 3 Diarrhea is common, with most episodes being short-lived. However, in the course of a year, approximately 5% of the US population experiences chronic diarrhea as defined by liquid stools lasting longer than 4 weeks. 4 Therefore, diarrhea is a major cause of morbidity. It is important to recognize that diarrhea is a symptom or sign, not a disease, and can be caused by numerous conditions. Given the multitude of possible causes, the evaluation and treatment of the patient with diarrhea can be challenging. An understanding of the basic mechanisms of diarrhea can help facilitate diagnosis and management.

Pathophysiology

The fundamental process causing all diarrheal diseases is incomplete absorption of water from intestinal luminal contents. Water itself is not actively transported across the intestinal mucosa but moves across secondary to osmotic forces generated by the transport of solutes, such as electrolytes and nutrients. Normally, absorption and secretion take place simultaneously, but absorption is quantitatively greater. Either a decrease in absorption or an increase in secretion leads to additional water within the lumen and diarrhea. Excess stool water then causes decreased stool consistency.

Thus, diarrhea is a condition of altered intestinal water and electrolyte transport. The pathophysiologic mechanisms of diarrhea include osmotic, secretory, inflammatory, and altered motility. Osmotic diarrhea involves an unabsorbed substance that draws water from the plasma into the intestinal lumen along osmotic gradients. Secretory diarrhea results from disordered electrolyte transport and, despite the term, is more commonly caused by decreased absorption rather than net secretion. Inflammatory diseases cause diarrhea with exudative, secretory, or osmotic components. Altered motility of the intestine or colon may alter fluid absorption by increasing or decreasing the exposure of luminal content to intestinal absorptive surface. However, from a pathophysiologic perspective, no single cause of diarrhea is truly unifactorial.

A Simplified 5-Step Approach

The initial approach to the patient with diarrhea is to obtain a detailed history and perform a physical examination. An understanding of the epidemiological settings in which diarrhea occurs (eg, community acquired, hospital acquired, or travel related) will also help direct diagnosis and treatment. Often, after history and physical examination, the cause of diarrhea is not obvious. In this situation, a simple 5-step evaluation ( Table 1 ) can facilitate the workup of the patient with diarrhea.

Simplified 5-Step Approach to Diarrhea

Does the Patient Really Have Diarrhea? Beware of Fecal Incontinence and Impaction

The first step in the clinical appraisal of the patient with diarrhea is to identify what the patient means by diarrhea . Fecal incontinence is often reported as diarrhea because of embarrassment associated with this condition rather than because the patient has any real difficulty distinguishing diarrhea from incontinence. 5 This possibility should be addressed by direct questioning and assessment of anal squeeze on digital examination. Incontinence is defined as the involuntary release of rectal contents. Continence requires intact anorectal structure and neuromuscular function. Although many incontinent patients have loose stools, their predominant problem is anal sphincter dysfunction and not dysregulated intestinal fluid or electrolyte absorption. If fecal incontinence is frequent, especially if it occurs in the absence of rectal urgency or loose stools, the patient should be evaluated for incontinence and not diarrhea.

Another condition that is often misinterpreted as diarrhea is fecal impaction. Patients with chronic constipation may develop fecal impaction from the inability to expel a large fecal mass through the anus. Rectal distention causes relaxation of the internal anal sphincter, and there is induction of secretions proximal to the obstructing stool. An overflow diarrhea results from liquid stool passing around the impaction and may be reported as diarrhea. A careful rectal examination will allow identification and treatment of this condition. 6

Rule Out Medications as a Cause of Diarrhea (Drug-Induced Diarrhea)

The second simple step is to consider medications as a potential cause of the diarrhea. Medications serve an important role in maintaining health and well-being. However, many medications are associated with adverse effects, particularly diarrhea. Drug-induced diarrhea is common because nearly all medications may cause diarrhea. 7 The key to diagnosing drug-induced diarrhea is to establish the temporal relationship between starting use of the drug and onset of diarrhea. The medications that most frequently cause diarrhea include antacids and nutritional supplements that contain magnesium, antibiotics, proton pump inhibitors, selective serotonin reuptake inhibitors, and nonsteroidal anti-inflammatory drugs.

The pathophysiology of drug-induced diarrhea is complex and varied. Drugs can cause diarrhea by several different mechanisms. 8 Specific mechanisms of drug-induced diarrhea may include activation of specific receptors and transporters, alteration in colonic bacterial flora, changes in mesenteric blood flow, provocation of intestinal inflammation, and apoptotic enteropathy. 9,10 Caffeine is an agent that may cause increased intestinal fluid secretion by elevating intracellular cyclic adenosine monophosphate levels. 11 Antibiotics alter colonic bacterial flora that may then decrease colonic bacterial fermentation of malabsorbed carbohydrates or lead to Clostridium difficile infection. Mesenteric vasoconstricting agents may decrease mesenteric blood flow and cause malabsorption. Nonsteroidal anti-inflammatory drugs or mycophenolate mofetil are agents that may incite intestinal inflammation, causing diarrhea. Lastly, diarrhea is common immediately after chemotherapy because these agents may cause intestinal or colonic crypt damage, thus impairing water absorption 12 and resulting in an apoptotic enterocolopathy.

To identify drug-induced diarrhea, it is imperative that the physician take a complete medication history and inquire about over-the-counter medications and supplements (eg, vitamin C and magnesium). Treatment involves withdrawal of the offending drug.

Distinguish Acute From Chronic Diarrhea

If a drug-induced cause of diarrhea seems unlikely, then the third step that can help direct evaluation is the duration of the diarrhea. The duration of diarrhea may be an important clue to the cause. Diarrhea is acute if it lasts fewer than 2 weeks and chronic if it lasts more than 4 weeks. The approach to acute diarrhea is straightforward because it is most commonly caused by infection and is self-limited. Often, no evaluation or treatment is required. However, stool testing and other studies are often indicated in the presence of certain clinical or epidemiological features, including age older than 65 years, immune compromise, volume depletion, hematochezia or blood-tinged stool, fever, severe abdominal pain, recent antibiotic use, known or suspected inflammatory bowel disease, community infectious disease outbreaks, and employment as a food handler. In contrast to acute diarrhea, chronic diarrhea typically warrants a diagnostic evaluation, is less likely to resolve on its own, and presents a broad differential diagnosis.

Categorize the Diarrhea as Inflammatory, Fatty, or Watery

If the patient has chronic diarrhea, then the fourth step is to categorize the diarrhea into inflammatory, fatty, or watery type on the basis of presentation and simple stool tests ( Figure ). Grouping patients with chronic diarrhea into one of these categories is most easily accomplished noninvasively at the front end of the evaluation by stool testing, a strategic initial step that will narrow the differential diagnosis and rationally direct the investigation.

Categorization of diarrhea. CT = computed tomography; EUS = endoscopic ultrasonography; SIBO = small intestinal bacterial overgrowth.

Inflammatory diarrhea is characterized by frequent, small-volume, bloody stools and may be accompanied by tenesmus, fever, or severe abdominal pain. Inflammatory diarrhea is suspected with the demonstration of leukocytes or leukocyte proteins (eg, calprotectin or lactoferrin) on stool examination. Other laboratory studies that may indicate an inflammatory diarrhea include elevated C-reactive protein level or sedimentation rate and low serum albumin level. Inflammatory diarrhea fundamentally indicates disrupted and inflamed mucosa, such as that caused by idiopathic inflammatory bowel disease (Crohn disease or ulcerative colitis), ischemic colitis, and infectious processes, such as C difficile , cytomegalovirus, tuberculosis, or Entamoeba histolytica . Radiation colitis and neoplasia are uncommon causes of inflammatory diarrhea. When history or stool analysis suggests chronic inflammatory diarrhea, flexible sigmoidoscopy or colonoscopy should be the initial study to look for structural changes.

Fatty stools are suggested by a history of weight loss, greasy or bulky stools that are difficult to flush, and oil in the toilet bowl that requires a brush to remove. 13 A common misconception is that floating stools are indicative of steatorrhea. Floating stools indicate gas production by colonic bacteria, not steatorrhea. 14 The basic mechanisms of chronic fatty diarrhea are malabsorption and maldigestion. Fat malabsorption results from inadequate mucosal transport, and fat maldigestion results from defective hydrolysis of triglycerides. Malabsorption is caused by mucosal diseases, most commonly celiac disease, whereas the maldigestion results from pancreatic exocrine insufficiency (eg, chronic pancreatitis) or inadequate duodenal bile acid concentration (eg, small intestinal bacterial overgrowth [SIBO] or cirrhosis). A simple test to screen for excess fecal fat is a Sudan stain, which will detect most cases of clinically significant steatorrhea. However, the criterion standard for steatorrhea is a quantitative measurement on a timed stool collection while patients consume a 100-g fat diet, and steatorrhea is defined as more than 7 g of fat per 24 hours. When fatty diarrhea is identified, the initial goal is to distinguish malabsorption from maldigestion. The evaluation focuses on looking for a structural problem involving the small intestine or pancreas. Endoscopy with small bowel biopsies allows evaluation of the small intestinal mucosa for celiac disease. Small bowel aspiration can be performed to look for SIBO, which causes steatorrhea by deconjugation of bile acids with resultant low duodenal bile acid concentrations. In addition, hydrogen breath tests may be used to diagnose SIBO. The diagnosis of SIBO requires consideration of a predisposing factor, such as intestinal stasis, achlorhydria, pancreatic insufficiency, or immune deficiency. If small bowel disease is excluded, computed tomography or endoscopic ultrasonography may be useful to identify morphological changes of chronic pancreatitis. If no intestinal abnormalities are found and there is no evidence of chronic pancreatitis, abnormal pancreatic exocrine function should be considered. An empiric trial of pancreatic enzyme supplementation may be used to assess for the presence of pancreatic exocrine insufficiency. If such a trial is conducted, high doses of enzymes should be prescribed, and some objective measurement, such as fecal fat excretion or weight gain, should be monitored to assess response. 10

Watery diarrhea can be further classified as osmotic or secretory in origin. Osmotic diarrhea is due to the ingestion of poorly absorbed ions or sugars. Secretory diarrhea is due to disruption of epithelial electrolyte transport. Two ways to distinguish an osmotic from a secretory process is by response to fasting and calculating the fecal osmotic gap. An essential characteristic of osmotic diarrhea is that stool volume decreases with fasting, whereas secretory diarrhea typically continues unabated with fasting. Another way to clinically differentiate osmotic diarrhea from secretory diarrhea is by calculating the fecal osmotic gap. The fecal osmotic gap is calculated by adding the stool sodium and potassium concentration, multiplying by 2, and subtracting this amount from 290 mmol/L. Measured stool osmolality should not be used because it largely reflects bacterial metabolism in vitro, not intraluminal osmolality. A fecal osmotic gap greater than 50 mmol/L suggests an osmotic cause for diarrhea, whereas a gap less than 50 mmol/L supports a secretory origin.

If a diagnosis of osmotic diarrhea is made, the differential diagnosis is limited and the evaluation is relatively straightforward. Osmotic diarrhea is usually due to ingestion of poorly absorbed cations (eg, magnesium) or anions (eg, phosphate, or sulfate), which are often contained in laxatives and antacids, or to carbohydrate malabsorption from ingestion of poorly absorbed sugars or sugar alcohols (eg, sorbitol or xylitol). Lactose intolerance is by far the most common type of carbohydrate malabsorption, with prevalence rates up to 100% in Africa, Asia, and Latin America. 15 Measuring a stool pH can help distinguish between osmotic diarrhea due to poorly absorbed ions and that due to poorly absorbed sugars. 16,17

Carbohydrate malabsorption will result in a stool pH less than 6 because as carbohydrates reach the colon they are fermented by bacteria, releasing short-chain fatty acids and making the stool water acidic. 15,16 Numerous disease processes can produce secretory diarrhea; the major causes are listed in Table 2 . The basic pathophysiologic mechanism involves either net secretion of ions (chloride or bicarbonate) or inhibition of net sodium absorption. 18 The most common cause of secretory diarrhea is infectious 18 ; however, infection is an uncommon cause of chronic secretory diarrhea. Therefore, noninfectious causes of secretory diarrhea should be sought. Of the many causes of secretory diarrhea, peptide-secreting endocrine tumors (eg, carcinoid or gastrinoma) deserve mention. Endocrine neoplasms are a rare cause of chronic diarrhea and account for less than 1% of patients who present with chronic diarrhea. 6 Therefore, the pretest probability of detecting a peptide-secreting tumor in an individual with chronic diarrhea is low, and there is a high probability of false-positive screening test results. 19 Hence, testing for peptide-secreting tumors should only be pursued if there is more direct evidence of one of these conditions. For example, an enlarged nodular liver, skin flushing, and wheezing would support small intestinal carcinoid metastatic to liver. Because diarrhea associated with endocrine neoplasms can cause significant morbidity and mortality, it is important for physicians to recognize the diarrheal syndromes associated with endocrine neoplasms ( Table 3 ). Once the type of diarrhea is categorized and the differential diagnosis minimized, directed testing can usually lead to a diagnosis.

Major Causes of Secretory Diarrhea

Endocrine Neoplasms Associated With Diarrhea

Consider Factitious Diarrhea

Factitious diarrhea is an intentionally self-inflicted disorder. The most frequent cause of factitious diarrhea is surreptitious laxative ingestion. Physicians usually assume that patients are being truthful, but up to 15% of patients who undergo an evaluation for chronic diarrhea may be surreptitiously ingesting laxatives. 20 The key to diagnosing factitious diarrhea is suspecting it. A factitious origin should be considered for persons in whom diarrhea remains undiagnosed after thorough evaluation.

Individuals with factitious diarrhea are most commonly women of higher socioeconomic status and often employed in the medical field. There is frequently a history of multiple medical consultations or hospitalizations in an effort to establish the cause of diarrhea. Evaluation of the patient with suspected factitious diarrhea consists of measuring stool osmolality, performing endoscopy, and analyzing stool water or urine for laxatives.

Measurement of stool osmolality can be useful in detecting factitious diarrhea caused by the addition of water or dilute urine to the stool. 21-23 Because stool osmolality can never be less than that of plasma, a low osmolality (<290 mOsm/kg) can only result by adding a hypotonic solution, such as water or urine, to stool. In addition, a very high stool osmolality (>600 mOsm/kg) may be a clue to stool diluted with hypertonic solutions, such as tomato juice or blood. 24 A stool osmolality of less than 600 mOsm/kg often indicates prolonged storage and carbohydrate fermentation. Therefore, a measured stool osmolality of less than 290 mOsm/kg or greater than 600 mOsm/kg is a potential clue to factitious diarrhea.

Colonoscopy may be helpful in evaluating factitious diarrhea. Pseudo–melanosis coli may be a potential clue found on colonoscopy. Pseudo–melanosis coli is a brownish discoloration of the colonic mucosa caused by the accumulation of lipofuscin pigment in macrophages of the lamina propria. 25 It occurs with the use of anthraquinone laxatives, such as senna, cascara, and rhubarb, and takes on average 9 months to develop. It is benign and reversible, disappearing within 1 year of discontinuing use of anthraquinone laxatives. 26 Before confronting the patient with this finding, it is important to realize that pseudo–melanosis coli is not pathognomonic for anthraquinone laxative use and may be seen in other conditions that cause chronic colonic inflammation. In addition, patients may be unaware that they are ingesting anthraquinone like laxatives because they may be “natural” ingredients in herbal teas and other health supplements. Finally, if measurement of stool osmolality and colonoscopy do not provide potential clues to factitious diarrhea, then stool, urine, and serum can be tested for laxatives.

The following 3 cases illustrate the application of the simplified 5-step approach to the patient with diarrhea.

Applying the 5-Step Approach

A 50-year-old man with type 2 diabetes mellitus presents with a 6-month history of diarrhea. He has up to 10 explosive watery stools a day with occasional fecal incontinence. There is no associated bleeding or pain. He has not lost weight. Complete blood cell count and chemistry analysis results are unremarkable for contributing conditions. Prior testing shows multiple negative stool study results for white blood cells, occult blood, and pathogens. He had a normal flexible sigmoidoscopy with biopsy result. A serologic test result for celiac disease with tissue transglutaminase antibodies was negative.

This patient with diabetes mellitus appears to have chronic diarrhea with fecal incontinence as a complication and not primary contributor to symptoms. When applying the simple 5-step approach to diarrhea further, the next step is to consider a drug-induced cause. Further history in this case revealed that the patient was prescribed metformin 2 weeks before the onset of symptoms. By far the most common cause of diarrhea in those with type 2 diabetes is therapy with metformin. 27 This case illustrates the importance of taking a detailed medication history in the patient with chronic diarrhea. A medication history is particularly salient in the diabetic patient because medications such as metformin and acarbose commonly cause diarrhea. Features of metformin-induced diarrhea include watery stools that are often explosive and associated with fecal incontinence. The resolution of diarrhea after cessation of metformin therapy is indicative of this diagnosis. Other causes of chronic diarrhea to consider in diabetic patients include celiac disease, microscopic colitis, exocrine pancreatic insufficiency, “sugar-free” foods that may contain poorly absorbable sugar alcohols, and bile acid malabsorption.

A 25-year-old Asian woman presents with intermittent diarrhea, abdominal bloating, and excess flatus for the past 5 years. Several times per week she experiences mild cramping abdominal pain that is followed by explosive watery bowel movements with a large amount of flatus. She denies blood in stool, fever, weight loss, anorexia, or fecal incontinence. She has not traveled internationally or taken any antibiotics. She takes no medications and has not been able to associate her symptoms with dietary triggers. Physical examination reveals normal thyroid, no hepatomegaly, and no rashes. Laboratory studies reveal a normal complete blood cell count. Stool studies performed during an episode of diarrhea show a sodium level of 80 mmol/L, a potassium level of 30 mmol/L, and stool pH of 5.

This individual has intermittent diarrhea without fecal incontinence. She takes no medications, making a drug-induced cause unlikely. Symptoms have persisted for more than 4 weeks, making this chronic diarrhea and unlikely to be infectious in origin. The next step in the simplified 5-step approach would be to categorize the diarrhea as inflammatory, fatty, or watery. An inflammatory cause is unlikely given the absence of fever, severe abdominal pain, or blood in stool. She has lost no weight and has no descriptors, such as oil droplets in toilet water or difficult to flush stools, which would raise suspicion for fatty stools. Correct categorization of the stools in this case would be watery diarrhea. The next step when confronted with a chronic, watery diarrhea is to determine whether it is an osmotic or secretory process by calculating the stool osmotic gap. In this case, the patient had a stool osmotic gap (290 − 2[80+30]) of greater than 50 mmol/L, suggesting an osmotic cause of diarrhea. The evaluation of osmotic diarrhea is relatively straightforward because there are only a few causes. The 2 major causes of osmotic diarrhea are ingestion of poorly absorbed ions, such as magnesium, or ingestion of poorly absorbed sugars. Assessing the pH of stool water helps to distinguish these 2 conditions. Carbohydrate malabsorption will result in a stool pH less than 6 because as carbohydrates reach the colon they are fermented by bacteria, releasing short-chain fatty acids and making the stool water acidic. 15,16 Stool analysis in this case revealed a stool pH of 5, which is indicative of colonic fermentation of malabsorbed carbohydrates. Initially, the patient did not associate any of her symptoms with dietary triggers; however, on further questioning there was some correlation of symptoms with ingestion of milk products. Subsequently, her symptoms improved on a lactose-free diet. Intolerance to lactose-containing foods (primarily dairy products) is common, with a particularly high prevalence in Asians. Ingestion of the disaccharide lactose requires digestion by the disaccharidase lactase to its constituent components of glucose and galactose to permit absorption because monosaccharides are the only sugars absorbed across the small intestinal epithelium. Absence of disaccharidases as in lactase deficiency results in an osmotic diarrhea, abdominal pain, and excess flatulence.

An 80-year-old woman with hypertension presents with a 3-year history of nonbloody diarrhea. She reports 3 to 6 moderate-sized bowel movements per day without a nocturnal component. Her appetite is intact, and she has had no fever, weight loss, or blood in the stool. She has occasional fecal incontinence, but these episodes are less common now because she does not eat out and stays home to be close to the bathroom. She has tried eliminating milk products, gluten, and caffeine from her diet without improvement. Physical examination revealed a woman physically younger than her stated age, and rectal examination revealed adequate resting and squeeze anal sphincter tone without stool in the rectum. Laboratory studies revealed a normal complete blood cell count. Colonoscopy revealed pseudo–melanosis coli.

The simple 5-step approach to diarrhea should be applied to this 80-year-old woman: (1) determine whether the patient really has diarrhea; (2) rule out medications as a cause of diarrhea; (3) distinguish acute from chronic diarrhea; (4) categorize the diarrhea as inflammatory, fatty, or watery; and (5) consider factitious diarrhea.

The patient appears to have diarrhea that is complicated by mild fecal incontinence. A drug-induced cause is unlikely based on review of medications. The duration of the diarrhea is greater than 4 weeks, indicating it is chronic. The diarrhea is watery because there are no symptoms or signs of inflammatory diarrhea, and the absence of weight loss makes fatty diarrhea unlikely. Stool electrolytes reveal no fecal osmotic gap, indicating a secretory origin. On the basis of the differential diagnosis of secretory diarrhea and considering the patient's demographic features, a colonoscopy was performed to evaluate for microscopic colitis. The colonoscopy revealed pseudo–melanosis coli, suggestive of anthraquinone laxative use; however, she denied laxative ingestion. On further questioning, the patient admitted to drinking herbal tea on a daily basis. The tea contained sennosides, which are hydroxyanthracene glycosides derived from senna leaves. Her diarrhea resolved when she stopped drinking the herbal tea. This case illustrates 2 important points. First, a complete dietary history is crucial when evaluating the patient with chronic diarrhea. Second, when confronted with chronic, secretory diarrhea, it is helpful to review its differential diagnosis and pursue testing based on clinical suspicion.

Evaluation of the patient with diarrhea can often be complex and time-consuming. Hence, a methodical approach to the patient with diarrhea can facilitate diagnosis and management. One such simplified method is the 5-step approach as outlined and applied in the clinical cases described in this report. This approach helps to limit the differential diagnosis and direct testing. It is meant as a guide for the physician and is not a substitute for a thorough history. With this approach, a large percentage of patients with diarrhea can be evaluated and treated by a primary care physician. More complex scenarios should be referred to a gastroenterologist.

Acknowledgments

The author thanks Dr David A. Ahlquist for his valuable critique of the submitted manuscript.

Supplemental Online Material

Author Interview Video

Pediatric Gastroenteritis Clinical Presentation

• Author: Randy P Prescilla, MD; Chief Editor: Russell W Steele, MD  more...
• Sections Pediatric Gastroenteritis
• Practice Essentials
• Pathophysiology
• Epidemiology
• Physical Examination
• Laboratory Studies
• Imaging Studies
• Other Tests
• Medical Care
• Medication Summary
• Antibiotics
• Antiemetics
• Further Outpatient Care
• Further Inpatient Care
• Deterrence/Prevention

The history and physical examination serve 2 vital functions: (1) differentiating gastroenteritis from other causes of vomiting and diarrhea in children and (2) estimating the degree of dehydration. In some cases, the history and physical examination can also aid in determining the type of pathogen responsible for the gastroenteritis, although only rarely will this affect management.

Determine the duration of diarrhea, the frequency and amount of stools, the time since the last episode of diarrhea, and the quality of stools. Frequent, watery stools are more consistent with viral gastroenteritis, while stools with blood or mucous are indicative of a bacterial pathogen. Similarly, a long duration of diarrhea (>14 days) is more consistent with a parasitic or noninfectious cause of diarrhea.

Determine the duration of vomiting, the amount and quality of vomitus (eg, food contents, blood, bile), and time since the last episode of vomiting. When symptoms of vomiting predominate, one should consider other diseases such as gastroesophageal reflux disease (GERD), diabetic ketoacidosis, pyloric stenosis, acute abdomen, or urinary tract infection.

Determine if there is an increase or decrease in the frequency of urination as measured by the number of wet diapers, time since last urination, color and concentration of urine, and presence of dysuria. Urine output may be difficult to determine with frequent watery stools.

Abdominal pain

Determine the location, quality, radiation, severity, and timing of pain, based on a report from the parents and/or child. In general, pain that precedes vomiting and diarrhea is more likely to be due to abdominal pathology other than gastroenteritis.

Signs of infection

Determine the presence of fever, chills, myalgias, rash, rhinorrhea, sore throat, cough, known immunocompromised status. These may indicate evidence of systemic infection or sepsis.

Appearance and behavior

Elements include weight loss, quality of feeding, amount and frequency of feeding, level of thirst, level of alertness, increased malaise, lethargy, or irritability, quality of crying, and presence or absence of tears with crying.

A history of recent antibiotic use increases the likelihood of Clostridium difficile infection.

History of travel to endemic areas may make prompt consideration of organisms that are relatively rare in the United States, such as parasitic diseases or cholera.

Elements of the physical examination are as follows:

General - Weight, ill appearance, level of alertness, lethargy, irritability

HEENT (head, ears, eyes, nose, and throat) - Presence or absence of tears, dry or moist mucous membranes, and whether the eyes appear sunken

Cardiovascular - Heart rate and quality of pulses

Respiratory - Rate and quality of respirations (deep, acidotic breathing suggests severe dehydration).

Abdomen - Abdominal tenderness, guarding and rebound, and bowel sounds; abdominal tenderness on examination, with or without guarding, should prompt consideration of diseases other than gastroenteritis

Back - Flank/costovertebral angle tenderness increase the likelihood of pyelonephritis

Rectal - Quality and color of stool, presence of gross blood or mucous

Extremities - Capillary refill time, warm or cool extremities

Skin - Abdominal rash may indicate typhoid fever (infection with  Salmonella typhi ), while jaundice might make viral or toxic hepatitis more likely; slow return of abdominal skin pinch suggests decreased skin turgor and dehydration, while a doughy feel to the skin may indicate hypernatremia

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Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev . 2012. 6:CD005436. [QxMD MEDLINE Link] .

Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med . 2006 Jan 5. 354(1):11-22. [QxMD MEDLINE Link] .

Linhares AC, Velazquez FR, Perez-Schael I, Saez-Llorens X, Abate H, Espinoza F. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study. Lancet . 2008 Apr 5. 371(9619):1181-9. [QxMD MEDLINE Link] .

Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten M, Louw C. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med . 2010 Jan 28. 362(4):289-98. [QxMD MEDLINE Link] .

Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM. Effect of rotavirus vaccination on death from childhood diarrhea in Mexico. N Engl J Med . 2010 Jan 28. 362(4):299-305. [QxMD MEDLINE Link] .

Phavichitr N, Catto-Smith A. Acute gastroenteritis in children : what role for antibacterials?. Paediatr Drugs . 2003. 5(5):279-90. [QxMD MEDLINE Link] .

Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev . 2011. (9):CD005506. [QxMD MEDLINE Link] .

Freedman SB, Hall M, Shah SS, Kharbanda AB, Aronson PL, Florin TA, et al. Impact of increasing ondansetron use on clinical outcomes in children with gastroenteritis. JAMA Pediatr . 2014 Apr. 168(4):321-9. [QxMD MEDLINE Link] .

Freedman SB, Adler M, Seshadri R, Powell EC. Oral ondansetron for gastroenteritis in a pediatric emergency department. N Engl J Med . 2006 Apr 20. 354(16):1698-705. [QxMD MEDLINE Link] .

Borowitz SM. Are antiemetics helpful in young children suffering from acute viral gastroenteritis?. Arch Dis Child . 2005 Jun. 90(6):646-8. [QxMD MEDLINE Link] .

• Table 1. Assessment of Dehydration [ 2 ]
• Table 2: Assessment of Dehydration [ 23 ]

Contributor Information and Disclosures

Randy P Prescilla, MD Instructor in Anesthesia, Harvard Medical School; Assistant in Perioperative Anesthesia, Children's Hospital Boston Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha , American Academy of Pediatrics , American Society for Microbiology , Infectious Diseases Society of America , Pediatric Infectious Diseases Society , Phi Beta Kappa Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics, Novavax, Regeneron, Diassess, Actelion<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur.

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics , American Association of Immunologists , American Pediatric Society , American Society for Microbiology , Infectious Diseases Society of America , Louisiana State Medical Society , Pediatric Infectious Diseases Society , Society for Pediatric Research , Southern Medical Association Disclosure: Nothing to disclose.

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Case-based learning: acute diarrhoea

SCIENCE PHOTO LIBRARY

After reading this article, you should be able to:

• Understand the various causes of acute diarrhoea
• Elicit the necessary information to guide management
• Effectively manage patients presenting with acute diarrhoea
• Know when to refer patients for medical review

Diarrhoea is defined as the passage of three or more loose stools in 24 hours, or defecation more frequent than what is normal for an individual ​[1]​ . Diarrhoea can be classified as:

• Acute — symptoms lasting less than 14 days;
• Persistent — symptoms lasting more than 14 days; or 
• Chronic — symptoms of more than 4 weeks duration ​[1]​ .

This article discusses the diagnosis and management of acute diarrhoea and when pharmacists should refer patients for a further medical opinion.

Acute diarrhoea has a considerable impact on UK morbidity. Approximately 50% of acute diarrhoea patients report absence from work or school and around 25% of the UK population is affected by infectious diarrhoea annually ​[2,3]​ . During the winter months, gastroenteritis also carries a significant financial burden, costing the NHS an estimated £7m to £10m per year owing to resultant hospital bed closures and staff sickness ​[4]​ . 

Taking an accurate history is essential when assessing patients with diarrhoeal symptoms. The assessment should determine the onset, duration, frequency and severity of symptoms, the presence of any red flags and attempt to determine the underlying cause. It is also important to assess patients for complications, such as dehydration ​[4]​ .

Children or adults presenting at a pharmacy with faecal urgency, abdominal cramps, abdominal pain, frequent passing of loose, watery faeces, nausea and/or vomiting need to be assessed carefully ​[4]​ . Immediate referral is required if the patient presents with any ‘Red flag’ symptoms and signs of significant disease, which are summarised in Box 1 . Although most episodes of diarrhoea tend to be short lived, self limiting and benign, identifying cases that represent potentially serious illness can be a challenge ​[4]​ .

Box 1: Red flag symptoms ​[5–8]​

Patients presenting with ‘one or more’ of the following symptoms should be referred:

• Feeling generally unwell with fever and vomiting — risk of severe dehydration; 
• Age <6 months with symptoms >24 hours duration — refer immediately and provide oral rehydration salts immediately; 
• Infants with sunken fontanelle;
• Age >6 months with symptoms >48 hours duration;
• Vomiting or unable to tolerate oral rehydration;
• Pre-existing medical conditions worsened by diarrhoea (e.g. diabetes, congestive heart failure);
• Immunocompromised or on immunosuppressive medications;
• Abdominal pain; 
• Blood or mucus in stool;
• Bleeding from rectum;
• Evidence of dehydration (e.g. skin turgor) or shock (e.g. tachycardia, systolic blood pressure <90mmHg, weakness, confusion, oliguria or anuria, marked peripheral vasoconstriction);
• Unintentional weight loss;
• Ongoing diarrhoea after recent completion of an antibiotic course;
• Nocturnal symptoms; 
• Abdominal or rectal mass.

Pharmacists should use their clinical judgement when deciding on the urgency of the referral and whether it is necessary to refer to the GP or urgent care.

The majority (90%) of acute diarrhoea cases are associated with bacterial or viral infection ​[5]​ . Norovirus and  Campylobacter  are the most common diarrhoea-causing agents in the community ​[5]​ . Travellers’ diarrhoea can be caused by bacteria and parasites such as  Escherichia coli, Campylobacter, Shigella and Salmonella ​[9]​ .  

Other causes of acute diarrhoea include food allergies (products containing sorbitol), alcohol, excess stress, recent pelvic irradiation, medication side effects   (e.g. non-steroidal anti-inflammatory drugs [NSAIDs] or antibiotics) and acute flares of chronic inflammation, such as Crohn’s disease or ulcerative colitis, which affect water reabsorption in the colon resulting in loose and/or watery stools ​[7]​ .

There are many causes of acute diarrhoea in babies, most commonly viral gastroenteritis; however, the cause may be extra-intestinal (such as  mening i tis , chest infection,  ear infection  or a urinary tract infection) ​[5]​ .

Eliciting an accurate history of symptoms is the most effective way of diagnosing acute diarrhoea and will guide the choice of management. Box 2 summarises the questions pharmacists should ask to guide patient assessment.

Box 2: Questions to ask during a consultation with a patient experiencing diarrhoea 

“When  did it start?” 

Onset of symptoms:

• Within one to two days of ingesting food suggests contaminated food ( Staphylococcus aureus, Salmonella or E. coli ,  Bacillus cereus  toxin or norovirus) ​[10,11]​

“What  does it look like?”

Amount, consistency and frequency ​[12]​ :

• Higher volume and/or frequency of watery stools;
• Blood, mucus and/or pus in stools suggest severe inflammation and/or infectious cause;
• Mucus and pus indicate a chronic inflammatory cause or infective pathogen. 

“How  do you feel?”

Associated symptoms:

• Pain, bloating, nausea, vomiting, fever, tenesmus;
• Thirsty but no appetite;
• What does the patient look like? Ill or well, nutritional status, fever?

“Where  have you been recently?”

Travel, diet and lifestyle ​[6,9]​ :

• Recent travel or consumption of foods, such as meat, eggs, dairy or seafood, are suggestive of infection. Ask about any recent picnics or barbecues as well as water intake;
• Exposure to pets or cattle suggests infectious cause;
• Individuals who work in day care centres, hospitals or nursing homes suggests infection;
• Social history, such as sexual practice, alcohol use or drug use;
• Family history of cancer, irritable bowel disease (prevalence 0.5–1.0%), coeliac disease (prevalence of 0.5–1.0%) or irritable bowel syndrome (prevalence 10.0–13.0%).

Patients who are systemically unwell — such as those recently admitted to hospital and/or taking antibiotics, who have blood or pus in their stool, or who are immunocompromised — must be referred for further investigation involving routine microbiology of stool samples ​[3]​ .

Testing for  Clostridium difficile  infection is also warranted for patients who have recently completed a course of antibiotics, are on a proton pump inhibitor, have been recently discharged from hospital, or have recently returned from foreign travel ​[7]​ . Additional testing for ova, cysts and parasites, including amoebae,  Giardia or Cryptosporidium,  is also recommended following travel abroad,   particularly if diarrhoea is persistent (≥14 days) or the person has travelled to an at-risk area, such as Africa, Latin America, the Middle East and most parts of Asia ​[3,9]​ .  Box 3 summarises the diet and personal hygiene measures travellers should follow to reduce their risk of developing travellers’ diarrhoea.

Patient advice

It is important that pharmacists provide patients and carers with the following advice to help manage symptoms ​[13]​ .

• Stay at home and get plenty of rest;
• Drink lots of fluids, such as water or squash — take small sips if you feel sick;
• Eat when you feel able to — you do not need to eat or avoid any specific foods;
• Take  paracetamol  if you’re in discomfort — check the leaflet before giving it to a child.
• Carry on breast or bottle feeding your baby — if they’re being sick, try giving small feeds more often than usual;
• Give babies on formula or solid foods small sips of water between feeds;
• Have fruit juice or fizzy drinks — they can make diarrhoea worse;
• Make baby formula weaker — prepare formula at its usual strength;
• Give children aged under 12 years medicine to stop diarrhoea;
• Give aspirin to children aged under 16 years.

If the patient works with older people or young children, they may pose a risk of passing on the infection. Provide infection prevention and control advice as summarised below ​[13]​ :

• Wash your hands  with soap and water frequently;
• Wash any clothing or bedding that has faeces or vomit on it separately on a hot wash;
• Clean toilet seats, flush handles, taps, surfaces and door handles every day.
• Prepare food for other people, if possible;
• Share towels, flannels, cutlery or utensils;
• Use a swimming pool until two weeks after the symptoms stop.

Return to work should be delayed until 48 hours after symptoms resolve and if symptoms do not improve or resolve within 1 week of onset, the patient should ring NHS 111 or visit their GP for further investigation of the cause ​[13]​ .

There is a high risk of dehydration associated with acute diarrhoea, particularly in young children, frail people and older people ​[5,7,14]​ . It is important to assess the level of dehydration ( see Box 1 ) and determine whether referral is needed or if the patient can be safely managed with over-the-counter treatments, such as oral rehydration therapy (ORT). In severe dehydration (e.g. caused by dysentery and cholera), patients may require referral for intravenous hydration ​[5,7,14]​ .  

Oral rehydration therapy

Fluid and electrolyte depletion caused by diarrhoea is often prevented or reversed by ORT. Dehydration is the most common complication of acute diarrhoea and correction of hydration is best done with an orally administered low-osmolarity (i.e. hypotonic) alkaline rehydration solution containing glucose and sodium (240–250 mOsm/L) ​[5]​ . 

Each oral rehydration sachet (ORS) should be reconstituted with 200ml of water (freshly boiled and cooled water for children aged under 1 year) and may be kept at room temperature for up to 1 hour or in the fridge for up to 24 hours before discarding ​[5]​ . Frequent, small sips of refrigerated solutions may be more palatable and less likely to be regurgitated than giving a large volume quickly. When supplying ORS for children it may be helpful to provide an oral syringe for ease of administration. An alternative is to give the solution on a teaspoon or medicine spoon, or in a feeding bottle with a low flow teat. Administration of ORT to a healthy child is unlikely to cause any harm. Please see Table 1 for ORT recommendations.

Pharmacological treatment

Antidiarrhoeal agents are mostly opioid based and should only be used for short-term, rapid control of symptoms (such as travellers’ diarrhoea), but should be avoided if infection suspected ( see Case 1 ) ​[9]​ . Their use is limited by their actions on the central nervous system (CNS), which include CNS depression and the risk of dependence. Long-term use can also cause serious complications, such as toxic megacolon.   

Loperamide is the antidiarrhoeal of choice for travellers, but should be avoided if blood or mucus is present in stools ​[9]​ . The recommended dosage is 4mg initially, followed by 2mg after each loose stool, up to 12mg a day for a maximum of 2 days if supplied over the counter or up to 16mg a day if prescribed ​[9]​ . In patients with short bowel syndrome, higher doses of orodispersible tablets should be prescribed owing to rapid intestinal transit times and minimal absorption ​[16]​ . The Medicines and Healthcare products Regulatory Agency reports serious cardiac adverse reactions at high doses and recommends caution ​[17]​ . Notable side effects include drowsiness, headache, constipation, nausea and flatulence. 

Codeine increases the risk of colonic perforation if used in acute infective diarrhoea and should not be recommended ​[18,19]​ . However, in stoma patients with shorter transit time and reduced absorption, codeine is given at doses of 15–30mg up to every 4 hours, titrated to response ​[19]​ . Pharmacists should monitor patients for the usual opioid side effects, such as drowsiness and constipation ​[19]​ .

Antimotility agents

Antimotility drugs should not be used in patients with a high fever or blood and/or mucus present in their stool (dysentery), or in confirmed  E. coli  (VTEC) or  Shigellosis  infections ​[20]​ .

Co-phenotrope (atropine 25 micrograms and diphenoxylate 2.5mg) is licensed as an adjunct to rehydration in acute diarrhoea but effectiveness is debatable. The recommended dosage is four tablets initially followed by two tablets every six hours until diarrhoea is controlled ​[20]​ . 

Racecadotril, an enkephalinase inhibitor, is licensed as an adjunct to rehydration. It is currently not available in the UK for adults and the Scottish Medicines Consortium advised against the use in children owing to insufficient evidence ​[21]​ .

Antibiotics

Antibiotics are not recommended in view of the infection being most likely viral, but are occasionally used for prophylaxis of travellers’ diarrhoea (e.g. ciprofloxacin) ​[22]​ .

Advice for continuing care

In most cases, acute diarrhoea symptoms resolve within five to seven days ​[7,13]​ .

Individuals should not return to work until 48 hours after their symptoms have resolved ​[13]​ . If symptoms do not improve or resolve after a week, the patient should be referred for further investigation ​[13]​ . 

It is essential to maintain good hydration with ORT ​[13]​  and antidiarrhoeals must be stopped immediately if symptoms of ileus, constipation or abdominal distension are present ​[23]​ .

Box 3: Diet and personal hygiene measures to prevent travellers’ diarrhoea ​[9]​

Foods and beverages to be avoided while travelling: 

• Raw or undercooked meats, fish and seafood;
• Unpasteurised milk, cheese, ice cream and other dairy products;
• Tap water and ice cubes;
• Cold sauces and toppings;
• Ground-grown leafy greens, vegetables and fruit;
• Cooked foods that have stood at room temperature in warm environments;
• Food from street vendors, unless freshly prepared and served piping hot.

Hygiene measures:

• Render water potable by either bringing it to a boil or treating it with chlorine or iodine preparations and filtering with a filter of 1μm or less;
• Wash hands before and after eating.

Case studies

Case 1: Adult patient with acute diarrhoea

A woman aged 39 years presents to her local pharmacy requesting loperamide and co-codamol.

Consultation

The woman reports up to 10 episodes of watery diarrhoea in the past 24 hours. There are no obvious signs of blood or mucus in her stool. She has no appetite, is thirsty and has occasional cramping but no other pain .  She has two children at the local school and works as a community carer for older people. She needs to go back to work owing to staff shortages.

Assessment 

Viral or bacterial infection is the most likely cause with some signs of dehydration, thirst and dizziness. Cramping mainly on emptying her bowels and no pain making a flare of chronic diarrhoea less likely. No possible underlying causes identified,   such as any recent surgery, faecal incontinence or overflow diarrhoea resulting from constipation. She is not immunocompromised and has no history of chronic bowel disease. The patient is exhibiting no red flag symptoms, therefore referral to her GP is not required. 

Recommend ORS as the mainstay of management and explain that acute diarrhoea usually resolves within five to seven days ​[15]​ . An antidiarrhoeal should be used with caution as acute diarrhoea is a defence mechanism and there is a risk of toxic megacolon. Antibiotics are not indicated without microbiological tests. Advise   her to drink water and isotonic sports drinks (e.g. Lucozade) to provide potassium but to avoid hypertonic sugary or fizzy drinks, fruit juices and milk, which can worsen symptoms owing to damage to the intestinal lining caused by infecting organisms ​[13,24,25]​ . Recommend the consumption of easily digestible foods with high water content, such as soup or broth containing sodium. Provide infection prevention and control advice. Return to work should be delayed until 48 hours after symptoms resolve, and if symptoms do not improve or resolve within seven days of onset, she should visit her GP for further investigation of the cause ​[13]​ .

Case 2: Paediatric patient

A woman comes into the pharmacy on a Saturday afternoon asking for advice on diarrhoea management for her son who is six months old. The mother states she has kept him home from nursery as he hasn’t quite been himself and is a bit clingier than usual. He is requesting breast feeds more frequently and urine in his nappy is dark yellow in colour.

The mother says the baby has had watery diarrhoea for around 36 hours. He has no other medical conditions, is not receiving medication and she has not taken any actions so far. The baby has not vomited and has no fever, but looks quite pale with cold hands and has a slightly sunken fontanelle.

The child is already at a high risk of dehydration owing to his age and is displaying signs of clinical dehydration, such as dark urine, pallor, cold hands and a sunken fontanelle. Other red flag symptoms, such as the duration of diarrhoea, warrant referral ​[5]​ .

Advice 

The mother should be signposted to the local out-of-hours GP or hospital emergency department for assessment, but she should be supplied with and advised on the use of ORS so that treatment can commence immediately in case of clinical delay.

Reassure her that diarrhoea is usually self-limiting and manageable at home with ORS and can last five to seven days, but that it should stop within two weeks ​[5]​ . Provide infection prevention and control advice, delay return to nursery until 48 hours after symptoms resolve and advise to keep away from swimming pools for two weeks. Advise not to make formula weaker or give fruit juice as it can make diarrhoea worse ​[13]​ .

Case 3: Travellers’ diarrhoea

A 25-year-old male patient presents at the pharmacy with complaints of diarrhoea (approximately 5 times per day), abdominal pain and nausea for the past 3 to 4 days. He also complains of dry mouth, abdominal cramping and overall malaise. He states that he recently travelled to India on an adventure trip and has returned the day before. 

The patient did not receive any vaccinations or medications prior to travel and has not received antibiotics in the past five years. He reports no blood in the stool. He was on the return journey when the symptoms started so has not sought any professional advice.

Travellers’ diarrhoea is, for most people, a short-lived, self-limiting illness with recovery in a few days [6]. If the patient complains of blood in the stool and intermittent fevers and dehydration, he should seek medical advice as soon as possible ​[9]​ . 

ORS is the treatment of choice for mild travellers’ diarrhoea ​[9]​ . As a rough guide, advise to drink at least 200ml after each watery stool. This extra fluid should be taken in addition to what the patient would normally drink ​[9]​ . If the patient is vomiting, advise to wait five to ten minutes and then start drinking again but more slowly. Advise them to take a sip every two to three minutes but make sure that the total intake is as described above ​[26,27]​ .

It used to be advised to avoid eating for a while; however, it is now advised to eat small, light meals if possible, such as plain bread or rice. Continue with fluids and avoid fatty, spicy or ‘heavy’ food ​[9]​ .

Loperamide or bismuth preparations can be considered for short-term treatment (two days). Advise the person not to use loperamide or bismuth subsalicylate if they have blood or mucus in the stool and/or high fever or severe abdominal pain, but seek medical advice ​[9]​ .

This article was amended on 1 September 2021 to clarify that the codeine dose is every four hours, not up to 4 per hour, and the maximum daily dose of loperamide is 12mg when supplied over the counter and 16mg when prescribed.

Useful resources

• NHS: Diarrhoea and/or vomiting advice sheet (gastroenteritis) — advice for parents and carers of children
• National Travel Health Network and Centre (NATHAC) : Travel health information aimed at healthcare professionals advising travellers and people travelling overseas from the UK
• NHS: Diarrhoea and vomiting
• www.patient.info: Travellers’ diarrhoea patient information
• www.patient.info: Gastroenteritis in children patient information
• www.patient.info: Food poisoning in children patient information
• Medicines for Children: Oral rehydration salts patient information leaflet
• 1 Diarrhoeal disease fact sheet. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease (accessed Jul 2021).
• 2 Sandmann FG, Jit M, Robotham JV, et al. Burden, duration and costs of hospital bed closures due to acute gastroenteritis in England per winter, 2010/11–2015/16. Journal of Hospital Infection 2017; 97 :79–85. doi: 10.1016/j.jhin.2017.05.015
• 3 Managing Suspected Infectious Diarrhoea: Quick Reference Guide for Primary Care. Public Health England. 2015. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/409768/Managing_Suspected_Infectious_Diarrhoea_7_CMCN29_01_15_KB_FINAL.pdf (accessed Jul 2021).
• 4 Arasaradnam RP, Brown S, Forbes A, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut 2018; 67 :1380–99. doi: 10.1136/gutjnl-2017-315909
• 5 Diarrhoea and vomiting caused by gastroenteritis diagnosis, assessment and management in children younger than 5 years. NICE clinical guideline [CG84]. National Institute for Health and Care Excellence. 2009. https://www.nice.org.uk/guidance/cg84/resources/full-guideline-pdf-243546877 (accessed Jul 2021).
• 6 Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut 2007; 56 :1770–98. doi: 10.1136/gut.2007.119446
• 7 Diarrhoea – adult’s assessment. National Institute for Health and Care Excellence. 2018. https://cks.nice.org.uk/diarrhoea-adults-assessment#!topicSummary (accessed Jul 2021).
• 8 Oral rehydration salts. Information for parents and carers leaflet. Medicines for Children. https://www.medicinesforchildren.org.uk/oral-rehydration-salts (accessed Jul 2021).
• 9 Diarrhoea prevention advice for travellers. Clinical Knowledge Summary. National Institute for Health and Care Excellence. https://cks.nice.org.uk/topics/diarrhoea-prevention-advice-for-travellers/background-information/causes (accessed Jul 2021).
• 10 Food poisoning. NHS Inform. https://www.nhsinform.scot/illnesses-and-conditions/infections-and-poisoning/food-poisoning (accessed Jul 2021).
• 11 BAM Chapter 14: Bacillus cereus. US Food & Drug Administration. https://www.fda.gov/food/laboratory-methods-food/bam-chapter-14-bacillus-cereus (accessed Jul 2021).
• 12 Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clinical Infectious Diseases 2017; 65 :e45–80. doi: 10.1093/cid/cix669
• 13 UK conditions: Diarrhoea and vomiting. NHS. https://www.nhs.uk/conditions/diarrhoea-and-vomiting (accessed Jul 2021).
• 14 Dehydration. NHS. https://www.nhs.uk/conditions/dehydration (accessed Jul 2021).
• 15 Gastroenteritis. NICE clinical knowledge summary. National Institute for Health and Care Excellence. 2019. https://cks.nice.org.uk/gastroenteritis#!topicSummary (accessed Jul 2021).
• 16 Owen S. Can high dose loperamide be used to reduce stoma output? . Specialist Pharmacy Service. 2019. https://www.sps.nhs.uk/wp-content/uploads/2019/04/UKMI_QA_Highdoseloperamide_updateSep-2018_FINAL_partial-update-Mar2019.pdf (accessed Jul 2021).
• 17 Loperamide (Imodium): reports of serious cardiac adverse reactions with high doses of loperamide associated with abuse or misuse. Gov.uk. 2017. https://www.gov.uk/drug-safety-update/loperamide-imodium-reports-of-serious-cardiac-adverse-reactions-with-high-doses-of-loperamide-associated-with-abuse-or-misuse (accessed Jul 2021).
• 18 Codeine phosphate 15mg tablets BP. Summary of product characteristics. Aurobindo Pharma – Milpharm Ltd. . medicines.org. https://www.medicines.org.uk/emc/product/11268 (accessed Jul 2021).
• 19 Pharmaceutical considerations for patients with stomas. Pharmaceutical Journal Published Online First: 2020. doi: 10.1211/pj.2020.20208146
• 20 Co-phenotrope drug monograph. British National Formulary. https://bnf.nice.org.uk/drug/co-phenotrope.html (accessed Jul 2021).
• 21 SMC advice racecadotril 10mg, 30mg granules for oral suspension (Hidrasec Infants®, Hidrasec Children®)SMC No.(818/12). Scottish Medicines Consortium. 2014. https://www.scottishmedicines.org.uk/medicines-advice/racecadotril-hidrasec-resubmission-81812 (accessed Jul 2021).
• 22 Diarrhoea (acute) treatment summary. British National Formulary. https://bnf.nice.org.uk/treatment-summary/diarrhoea-acute.html (accessed Jul 2021).
• 23 Cipla EU L. Loperamide 2mg Capsules. Summary of product characteristics. medicines.org.uk. 2020. https://www.medicines.org.uk/emc/product/10287/smpc (accessed Sep 2021).
• 24 Knott L. Gastroenteritis. Patient. 2017. https://patient.info/digestive-health/diarrhoea/gastroenteritis (accessed Jul 2021).
• 25 Lactose intolerance Causes. NHS. 2019. https://www.nhs.uk/conditions/lactose-intolerance/causes (accessed Jul 2021).
• 26 Hill DR, Ryan ET. Management of travellers’ diarrhoea. BMJ 2008; 337 :a1746–a1746. doi: 10.1136/bmj.a1746
• 27 Traveller’s diarrhoea. Patient. https://patient.info/travel-and-vaccinations/travellers-diarrhoea-leaflet (accessed Jul 2021).

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