Nausea and vomiting are symptoms of a wide variety of underlying conditions that may involve almost any organ system. Accordingly, when faced with a patient with vomiting, the differential is broad and includes gastrointestinal, infectious, central nervous system, drug reaction, and cardiac origins (Table 1). While the most common causes of nausea and vomiting are acute gastroenteritis, febrile systemic illness, and drug effects,⁵ one must also consider certain critical and emergent diagnoses such as Boerhaave syndrome, intracranial bleed or raised intracranial pressure, meningitis, diabetic ketoacidosis, myocardial ischemia, sepsis, gonadal torsion, abdominal inflammatory processes, bowel obstruction, adrenal insufficiency, and toxic ingestions.

Table 1 Differential diagnosis of vomiting

Despite the heterogeneity in potential etiology, a thorough history and physical examination can often focus the approach and narrow the differential diagnosis. The American Gastroenterological Association (AGA) recommends a pragmatic 3-step approach to the management of the patient with nausea and vomiting.⁶ After a complete history and physical examination, the clinician should first correct any complications of vomiting such as hypokalemia, metabolic alkalosis, hypovolemia, ketosis, or vitamin deficiencies. Second, the underlying cause should be sought with the intention of initiating targeted therapy. The third step is the initiation of treatment strategies to suppress the symptoms. Although there are no clinical guidelines in the initial workup of the patient with vomiting, pregnancy testing should be considered in women of reproductive age. Serum electrolytes, complete blood count, liver function tests, lipase, urinalysis, and electrocardiogram may also be considered depending on the clinical situation.

Vomiting in the pediatric patient is an extremely common complaint in children presenting to the ED.²⁸ While most patients have a self-limiting disease process, vomiting may also be the presenting symptom for severe life-threatening conditions, and a thorough history and physical examination are therefore required to guide management. Clinicians have historically been cautious to prescribe antiemetics for children, a practice reinforced by the American Academy of Pediatrics’ (AAP) recommendation to use oral rehydration as first-line therapy for both mildly and moderately dehydrated children with gastroenteritis.²⁹ In a recent study, 73 children ranging in age from 8 weeks to 3 years with moderate dehydration from viral gastroenteritis were randomized to either oral rehydration therapy (ORT) or intravenous fluids. While nearly 50% of both groups were successfully rehydrated at 4 hours, subjects receiving ORT had shorter ED stays and were hospitalized less often. Based on their findings, the investigators opined that ORT was the preferred treatment option.³⁰

Despite these recommendations, a survey found 36% of pediatricians believed vomiting was a contraindication to ORT.³¹ The FDA’s 2006 black box warning on promethazine for pediatric patients younger than 2 years may have contributed to the hesitancy to use antiemetics and subsequently avoid ORT in children. Nonetheless, the past decade has also seen an increase in 5-HT₃ antagonists in the pediatric population. A double-blind, placebo-controlled study from 2002 on intravenous ondansetron for gastroenteritis found a reduction in admission rates for pediatric patients presenting with vomiting and an initial serum carbon dioxide level of 15 mEq/L or more.³²

Pharmacologic data demonstrating that orally administered ondansetron tablets are equivalent to its intravenous formulation have led to further investigations exploring whether intravenous access could be avoided. In 2006, investigators enrolled 215 children aged 6 months to 10 years treated in the ED for gastroenteritis-related dehydration. Compared with placebo, subjects who received ondansetron orally were less likely to vomit (14% vs 35%), had greater oral intake (239 mL vs 196 mL), and were less likely to require intravenous fluids (14% vs 31%).³³ Another pediatric study replicated these results, finding subjects who received oral ondansetron had a decreased need for intravenous fluids than those who received a placebo (21.6% vs 54.5%).³⁴ These results reinforce the practice of using oral ondansetron and ORT to treat pediatric patients with mild to moderate dehydration.

The differential diagnosis for diarrhea is broad, with several causes displaying overlapping signs and symptoms. A focused history including the onset, frequency, and character of the diarrhea (eg, presence of blood or mucus) as well as associated symptoms (eg, fever, vomiting), medical history (eg, human immunodeficiency virus [HIV], inflammatory bowel disease), medications, and travel history may aid in narrowing the differential. Nevertheless, there are several clinically noteworthy causes of diarrhea that have exceptional treatment regimens as well as important clinical ramifications to consider.

Clostridium difficile, which affects approximately 3 million patients yearly in the United States with a mortality rate of 1% to 2.5%,⁴² is caused by a disruption of normal intestinal flora,⁴³ and is responsible for 15% to 20% of antibiotic-related cases of diarrhea.⁴⁴ Severe C difficile infection may result in life-threatening complications such as toxic megacolon, intestinal perforation, sepsis, or death. Furthermore, diarrhea caused by C difficile may present with severe abdominal pain, high fever, and more than 10 watery stools per day; however, as it is common among elderly patients many or all of these signs and symptoms may be absent. One study found 15% of patients with diarrhea hospitalized at an academic center tested positive for C difficile,⁴⁵ while during times of outbreak more than 50% of patients in an affected ward may become colonized.⁴⁶ Of interest, although C difficile historically has not been thought of as a pediatric illness, recent evidence suggests the contrary. A pediatric ED-based study found that of specimens that underwent complete testing, 12.4% tested positive for C difficile toxin,⁴⁷ and nearly 3% of children tested positive for C difficile toxin in another similar study from France.⁴⁸ Recently a new disease pattern, community-onset C difficile–associated diarrhea, has emerged, and may occur without exposure to the typical risk factors including antibiotic usage.⁴⁹

Several agents have been implicated in the increased incidence of C difficile, including usage of antibiotics and proton pump inhibitors (PPIs). In one recent study, C difficile diarrhea among hospital inpatients was associated with the use of PPIs (9.3% of patients receiving PPIs vs 4.4% who did not receive PPIs) and receipt of 3 or more antibiotics.⁵⁰ Removing the inciting antibiotic treats up to 25% of cases of C difficile diarrhea.⁵¹ Antibiotic treatment regimens have traditionally used oral metronidazole (Flagyl) or vancomycin (Vancocin) for 14 days; however, for recurrent C difficile infection some experts recommend oral tapered-pulsed vancomycin (125 mg once a day for 1 week, 125 mg 3 times a day for 1 week, 125 mg every day for 1 week, 125 mg every other day for 2 weeks, 125 mg every third day for 2 weeks).⁵²

Traveler’s diarrhea, which affects 20% to 50% of individuals traveling from developed to developing countries and 4% to 9% of individuals traveling from developing to developed countries, is typically caused by enterotoxigenic Escherichia coli (ETEC) and enteroaggregative E coli, which bind to the intestinal mucosa to cause diarrhea typically without fever.⁵³ Incubation periods for ETEC last between 10 hours and 3 days followed by 3 to 5 days of illness.⁵⁴ ETEC produces a noninvasive toxin that causes severe watery diarrhea, abdominal cramps, nausea, and (infrequently) fever.⁵⁵ Shigella species and Salmonella species are other important bacterial pathogens. Campylobacter jejuni, a bacteria that poses additional hazards because it has been implicated with acute cases of myocarditis, has emerged as another important cause of traveler’s diarrhea.⁵⁶ Electrolyte disturbances for patients with traveler’s diarrhea are rare, and therefore laboratory work is usually unnecessary.⁵⁷ Treatment of traveler’s diarrhea is centered on antibiotic therapy, such as ciprofloxacin (Cipro), trimethoprim-sulfamethoxazole (Bactrim; resistance common), azithromycin (Zithromax), and rifaximin (Xifaxan).⁵⁸ If the patient with suspected traveler’s diarrhea has more than 2 unformed stools per day, bloody stools, or fever (>37.8°C), treatment with antibiotics is advised.⁵⁹ A short, single-day course of ciprofloxacin, 500 mg twice a day, is usually successful at stopping the illness within 24 hours,⁶⁰ although other sources recommend a 3-day course of ciprofloxacin or rifaximin.⁶¹ Prophylactic administration of antibiotics for those traveling to developing countries is not typically recommended. However, in one placebo-controlled trial performed on United States travelers in Mexico, subjects who took rifaximin prophylactically had significantly reduced rates of diarrhea (53.70% for those taking placebo vs 14.74% for those taking rifaximin).⁶² Nonetheless, C difficile and Helicobacter pylori must also be on the differential among the traveler afflicted with diarrhea. Noninfectious origins need to be considered if there is no response to antimicrobials or antiparasitics and there is a protracted course. Nonbacterial causes include enteric viruses, viral hepatitis, influenza, giardia, Cryptosporidium, Cyclospora, Entamoeba, Strongyloides, and other less common parasites.

Cryptosporidiosis, which typically affects immunocompromised individuals (particularly HIV-infected persons) and may also affect immunocompetent persons (usually children younger than 5 years), causes diarrhea lasting 1 to 2 weeks, and may develop into life-threatening illnesses. Although it appears that nitazoxanide (Alinia) reduces the load of parasites and may be useful in immunocompetent persons, a recent review found there is no evidence for effective agents in the management of cryptosporidiosis.⁶³

The differential diagnosis for the pediatric patient with diarrhea is broad and includes pathogens such as E coli, Campylobacter, Shigella, Salmonella, and viruses. However, in recent years a newer strain of E coli has emerged in the pediatric population: enteroaggregative E coli. In a study of 1327 children younger than 1 year with acute gastroenteritis, enteroaggregative E coli was isolated significantly more often in inpatients (4.7%) and ED patients (10.0%) than from well children (1.4%).⁶⁴ Viral gastroenteritis caused by rotaviruses is another concern in the pediatric population. Among middle- and low-income countries, it is estimated rotaviruses are responsible for 600,000 to 870,000 pediatric deaths per year, resulting in up to 6% of all mortality in children younger than 5 years.⁶⁵ The majority of these deaths were due to dehydration, underscoring the importance of rehydration therapies for children. Implementation of the rotavirus vaccine shows promise. A 2004 review of 64 trials conducted on 21,070 children found the vaccine’s effectiveness at preventing diarrhea caused by rotavirus ranged from 22% to 89%.⁶⁶

Evaluation of hydration status often dictates the treatment of pediatric patients with diarrhea. While acute appendicitis must always remain on the differential diagnosis of the child with diarrhea, digital rectal examinations and nasogastric tubes rarely provide additional actionable information for pediatric patients.⁶⁶ Treatment of the pediatric patient with diarrhea centers on supportive care, with encouragement of fluids for mild to moderate cases, and in severe cases intravenous or nasogastric fluid replacement. Educating parents in the appropriate treatment of their child’s diarrhea is crucial. Whereas 52% of parents treated their child’s diarrhea with appropriate rehydration fluids and solutions, 13% of parents used treatments not recommended in the current Centers for Disease Control (CDC) guidelines, typically using antidiarrheal agents and fluids high in simple sugars.⁶⁷

Developed in 1975, the WHO standard oral rehydration solution consists of a high content of sodium (90 mmol/L) and has been found to be effective in the treatment of dehydration from acute gastroenteritis regardless of the etiology of the diarrhea.⁶⁸ Several newer products with lower sodium levels, including the WHO revised formula (75 mmol/L) and Pedialyte (45 mmol/L), may be better tolerated among pediatric patients. However, these products may not be appropriate for patients suffering from diarrhea caused by cholera, one of the most serious types of diarrheal disease that can cause rapid electrolyte loss. In an analysis of 7 trials of patients with cholera, the investigators found an increased number of patients with hyponatremia treated with hypoosmolar solutions compared with standard oral rehydration solutions, although the outcomes were similar.⁶⁹

Elderly patients afflicted with diarrhea tend to have longer hospital stays (7.4 days in patients older than 75 years versus 4.1 days in those patients 20 to 49 years old) and a higher mortality.⁷⁰ Age greater than 65 years is also considered an independent C difficile risk factor.⁷¹ In one ED-based study of 174 patients with diarrhea, it was found that age greater than 40 years with constant abdominal pain and diarrhea was predictive of a surgical etiology for their symptoms.⁷² Taken together, these factors should prompt the clinician to at times take a more aggressive and perhaps more comprehensive approach in attempting to search for the origin of diarrhea in the elderly patient.

Rehydration and electrolyte replacement remain cornerstones of treatment for patients with diarrhea. To accomplish this, the “BRAT” diet (bananas, rice, apple sauce, and toast) is often recommended, although evidence supporting its practice is limited. Loperamide (Imodium) has been shown to be efficacious in reducing the symptoms of diarrhea in undifferentiated patients with mild symptoms⁷³; however, there is scant evidence regarding its safety profile in patients with moderate or severe diarrhea.⁷⁴ A recent review did not find conclusive evidence supporting or refuting the usage of antimotility agents and adsorbents in controlling diarrhea in people with HIV/AIDS,⁷⁵ thus reinforcing the need for adjunct treatments such as fluid replacement. Nevertheless, one meta-analysis found that when combined with antibiotic therapy, loperamide was more efficacious than antibiotics alone in decreasing illness duration for adult patients with traveler’s diarrhea.⁷⁶ Antidiarrheal agents are not recommended in the treatment of pediatric patients with diarrhea, as they have potentially serious side effects in this population.⁷⁷

Antibiotics are the mainstay of treatment for patients with a suspected bacterial cause for their diarrheal symptoms. A study of 139 patients presenting with severe diarrhea characterized by one of either profuse watery diarrhea with dehydration, passage of stools containing mucus and blood, temperature greater than 38.4°C, passage of more than 6 soft stools in 24 hours, duration of illness of more than 48 hours, severe abdominal pain in a patient older than 50, or diarrhea in the elderly, found single-dose quinolone therapy shortened the duration of symptoms and was equally efficacious when compared with a 5-day antibiotic regimen.⁷⁸

Probiotics, which are found in yogurts, fermented milks, and dietary supplements, may help treat diarrheal diseases. In one randomized, double-blind, placebo-controlled study, consumption of a 100-g drink containing Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophilus twice daily during a course of antibiotics and 1 week after the antibiotic was finished resulted in an absolute risk reduction of 21.6% for the occurrence of antibiotic-associated diarrhea.⁷⁹ Another study noted probiotic organisms may be beneficial for 3 problems common in the elderly: undernutrition, constipation, and the capacity to resist infection.⁸⁰ A systematic review of the literature on probiotics, which examined 23 studies with 1917 participants, found probiotics reduced the risk of diarrhea at 3 days and the mean duration of diarrhea by 30 hours.⁸¹

Most preventive measures aimed at limiting the spread of diarrheal diseases focus on improving the quality of available water sources. Two studies found the addition of household-based water filters reduced the prevalence of diarrhea by 60% in Columbia⁸² and by 70% in rural Bolivia.⁸³ Further, one study found treating turbid water in rural Kenya with a disinfectant resulted in a 19% absolute reduction in the prevalence of diarrhea.⁸⁴ Communicable and diarrheal diseases are also major concerns for disaster-affected populations in camp settings. In treated households in Liberia, disinfectants reduced diarrheal prevalence by 83% compared with control households.⁸⁵ Other developing countries have instituted hand-washing campaigns. One, in urban squatter settlements in Pakistan, found campaigns promoting hand-washing reduced the incidence of diarrhea by 53% among children younger than 15 years.⁸⁶ A recent review, which examined 33 trials with more than 53,000 participants, found that interventions focused on improving the quality of drinking water were effective in preventing diarrhea, with interventions aimed at the household level more effective than those aimed at the source.⁸⁷

The cause of constipation is often multifactorial. While a 2007 review revealed a small number of publications addressing the etiologic factors of this very common problem,⁹² it was suggested that insufficient dietary fiber intake, inadequate fluid intake, decreased physical activity, side effects of drugs, hypothyroidism, sex hormones, and colorectal cancer obstruction may be responsible for constipation.⁹² Furthermore, the cause of constipation may also be related to abnormal bowel motility, anatomical rectal disorders, neurological disorders, or psychosocial issues (Table 3). A thorough review of the patient’s medications is advisable, as there are many different medications that secondarily contribute to constipation, such as calcium and iron supplements, opioids, anticonvulsants, antipsychotics, and antihistamines.⁸⁸ Constipation resistant to simple measures may be caused by painful anorectal conditions, irritable bowel syndrome (IBS), slow transit constipation, or obstructive defecation. Obstructed defecation is a broad term used to describe the inability to empty stool from the rectum, which may result from functional, metabolic, mechanical, or anatomical problems.⁹³ Mechanical and anatomical disorders causing obstructive defecation include Hirschsprung disease, rectocele, rectoanal intussusception, enterocele, sigmoidocele, and rectal prolapse.⁹⁴ Studies have found that obstructive defecation is a significant problem for middle-aged women. Obstructive defecation was self-reported and defined by difficulty in passing stool, hard stool, straining for more than 15 minutes, or incomplete evacuation, occurring at least weekly. In this study of 2109 subjects, 12.3% of women reported obstructive defecation at least once weekly. Risk factors correlated with patients developing obstructive defecation included a history of IBS, vaginal or laparoscopic hysterectomy, unemployment, use of 3 or more medications, symptomatic pelvic organ prolapse, history of urinary incontinence surgery, or other pelvic surgeries.⁹⁵

Table 3 Etiology of constipation

IBS, characterized by chronic abdominal pain and altered bowel habits without a clearly defined organic cause,⁹⁶ affects 10% to 15% of North Americans.^97,98 Attempts to standardize the diagnosis of IBS have been made, and the American Gastroenterology Association recommends clinicians use the Rome III criteria, last revised in 2005, to diagnose IBS.⁹⁹ These criteria require the presence of recurrent abdominal pain or discomfort at least 3 days per month as well as 2 or more of the following: improvement with defecation, onset associated with a change in form of stool, or onset associated with a change in frequency of stool. The Rome III diagnostic criteria for IBS must be fulfilled for 3 consecutive months with symptom onset at least 6 months before diagnosis.¹⁰⁰ Other symptoms that are not part of the Rome criteria but support the diagnosis of IBS include defecation straining, urgency, a feeling of incomplete bowel movement, passing mucus, and bloating. Four subtypes of IBS are recognized: IBS with constipation (hard stools ≥25% and loose stools <25% of bowel movements), IBS with diarrhea (loose stools ≥25% and hard stools <25% of bowel movements), mixed IBS (hard stools ≥25% and loose stools ≥25% of bowel movements), and unsubtyped IBS (insufficient abnormality of stool consistency to meet the other subtypes).

Pharmacologic intervention must be tailored to the specific subtype of IBS. While antidepressant therapy has been explored as treatment for IBS, a trial of 51 patients randomized to placebo, imipramine, or citalopram found none of these agents significantly improved global IBS end points.¹⁰¹ Antibiotics, specifically rifaximin, have also been tried in the treatment of IBS. A recent study of 80 patients randomized to rifaximin or placebo for 10 days found the group that received rifaximin had a greater improvement of IBS symptoms and a lower bloating score.¹⁰²