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Pediatric Care Online AAP Chapter 166: Constipation Peter F.

Belamarich, MD The term constipation, which denotes both a symptom and a chronic condition, refers to the infrequent elimination of large or hard stools that cause pain on defecation. In childhood, chronic constipation that is not caused by another condition is known by several different names, including dysfunctional stool retention, psychogenic constipation, and idiopathic, chronic, and functional constipation. The last group of terms, which reflects our lack of understanding of the cause and is not pejorative, is used in this chapter. Given that constipation encompasses both objective and subjective complaints that vary by age, it has defied a comprehensive standard definition. Several consensus groups have developed definitions of constipation; however, none of these definitions seems entirely satisfactory to all.[1] One expert consensus definition of constipation is presented in BOX 166-1.[2]

Constipation is a common symptom among children in the industrialized world. In parental surveys, from 16% to 37% of toddlers are reported to suffer from it.[3] Most often, constipation is a self-limited symptom relieved by dietary changes or transient laxative use. Functional constipation presents a challenge to the pediatrician, as suggested by the observation that the evaluation and treatment of constipation occupies a significant percentage of all referrals to pediatric gastroenterologic services, although these children rarely require an invasive procedure.[4] To pediatricians caring for chronically constipated children, treatment failure raises the question of Hirschsprung disease. Among referral populations, more than 90% of childhood constipation is functional; ultimately, 50% to 90% of these children are cured.[5]

The approach to chronically constipated children used by gastroenterologists is well within the scope of the primary care pediatric practice and represents a therapeutic opportunity with a good cure rate. The focus of this chapter is on identifying and treating children who have functional constipation. An evidence-based guideline, endorsed by the American Academy of Pediatrics, has been published on evaluating and treating constipation.[6]

Constipation Infrequent elimination of large or hard stools that cause straining or pain Chronic constipation in childhood not caused by an organic lesion may also be called: o Dysfunctional stool retention o Psychogenic constipation o Idiopathic constipation o Functional constipation One expert consensus defined constipation as any of the following:

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Passage of hard, scybalous, pebblelike, or cylindrical cracked stools Straining or painful defecation Passage of large stool that may clog the toilet Stool frequency < 3 times per week, unless breastfed Can present as pain, fecal soiling, urinary tract infection, or enuresis

Prevalence Common among children of the industrialized world Among referral populations > 90% of childhood constipation is functional. 5090% will be cured. Age o Of toddlers, 1637% suffer constipation at some time.

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Normal colonic function

Focal circular contractions Impede progress of luminal contents Allow solutes and water to be absorbed from liquid ileal effluent Progress of a relatively dehydrated fecal stream is achieved by contractile waves. Bolus of stool o Propelled to next colonic segment o Ultimately, stool arrives at the rectum. Defecation o Coordinated sequence of neuromuscular events o Involves reflexive and conscious components o At rest, continence is maintained by: Involuntary resting tonic contraction of smooth muscle cuff of internal anal sphincter Posterior turn of anal canal in relation to anterior angulation of rectal vault o When stool arrives in rectal ampulla, it causes: Distention of rectal walls Relaxation of internal anal sphincter, which lowers the pressure of the anal canal and allows the stool bolus to descend to the anal canal (rectoanal inhibitory reflex) o Control of defecation is a critically important social achievement in early childhood. o Voluntary (and learned) contraction of striated muscle of external sphincter and puborectalis sling muscles increases pressure in anal canal and makes the exiting angle more acute. o The Valsalva maneuver in combination with relaxation of the external anal sphincter and puborectalis sling permits defecation to proceed.

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Functional Stool is most often withheld in response to the rectoanal inhibitory reflex. The cause is not clear, but functional constipation may result from several distinct pathophysiologic events, including: Disorder of dynamics of defecation Problem with rectal sensation Disorder of colonic transit, leading to impacted, overly desiccated stool in colon Withholding o Commonly recognized clinical scenarios that result in constipation include: Painful anal fissures Perianal streptococcal cellulitis Traumatic toilet-training experiences Transient periods of dehydration, illness, or immobility

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History o o o

Stool withholding may figure prominently in the perpetuation of constipation after pain or an aversive experience. o Withholding behavior in the toddler or child is strongly self-reinforcing. Avoidance of painful bowel movements makes the stool harder and more painful to pass. Parental concern may unwittingly reinforce withholding behavior o Lack of privacy commonly found in some school lavatories can engender withholding by older children. o Studies have documented abnormalities in the dynamics of defecation. Most common is paradoxical contraction of the external anal sphincter and the puborectalis sling in response to the rectoanal inhibitory reflex, also called: o Rectoanal pelvic floor dyssynergia o Abnormal defecation dynamics o Anismus Dyssynergia is considered to be a learned phenomenon. Painful defecation and withholding antedate the clinical presentation of constipation by 15 years. In a significant subset of children who experience persistent constipation, withholding becomes entrenched and particularly difficult to unlearn. Sensory abnormalities o Megarectum The rectum is dilated, with chronic impaction. Associated with increase in sensory threshold to minimal rectal distention Associated with increase in minimal volume required to initiate the urge to defecate o May persist for several years o May contribute to relapses Slow transit of fecal stream through colon o Occurs predominantly in young women o Can occur in children o Unclear whether this is a primary problem or acquired epiphenomenon of more distal difficulties with defecation o Not easily differentiated clinically from normal-transit constipation o A unique therapeutic approach has not emerged. Dietary factors o Dietary fiber is believed to have an important role in promoting regular bowel habit. o Decreased fiber intake as a risk factor for childhood constipation has been documented, but overlap exists in fiber intake between cases and controls. o In infancy, the transition from breast milk or formula to whole cows milk or periods of excess protein intake are associated with constipation. o It is a myth that iron-containing formulas cause constipation.

Description of stools that child passes Frequency Consistency Caliber History of stool withholding (a positive history strongly supports functional constipation) Age of child at onset o If a newborn, whether child passed meconium in first day of life Toilet-training experience o Whether traumatic o Critical in toddlers and preschool children Diet historyhow constipation began o With transition to cows milk o During periods of high protein intake o With excessive cows whole milk consumption Complications

Fissures Bleeding Abdominal pain Anorexia Enuresis Urinary tract infection Distention and vomiting (not caused by functional constipation) Prior evaluation and treatment o Over-the-counter medicines o Home remedies o Alternative therapies o Culturally specific therapies Can be part of treatment plan if they pose no harm Change in urinary voiding pattern (possible occult spinal process affecting sacral nerves) o Stream o Continence Family history of: o Heritable conditions o Functional constipation Specific questions to address differential diagnosis of: o Hirschsprung disease o Endocrine, metabolic, and neurologic disease In infants o Delayed passage of meconium

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Physical Exam


An empty rectum raises the possibility of Hirschsprung disease, particularly in conjunction with any or all of following: o History of delayed passage of meconium o Explosive gush of stool on withdrawal o Hard impacted mass palpated in the pelvis or lower abdomen In infants with delayed passage of meconium o Anorectal manometry o Rectal suction biopsy o Unprepared barium enema o Sweat test Impactions o Unusual o May indicate Hirschsprung disease External examination of perineal area o Establish the normal placement of anal orifice. o Look for: Anal fissure Skin tag Normal anal wink Examine lower extremities for: o Tone o Strength o Symmetry o Reflexes Examine spine for: o Dimple o Hair tuft o Vertebral anomalies


Check the childs growth parameters. Recent growth velocity For growth failure, failure to thrive, or short stature, consider: Thyroid function tests Celiac panel Sweat test Assess physical appearance. o The child should appear well and not wasted or malnourished. o Abdomen should not be distended. Examination should establish presence or absence of fecal impaction in lower quadrants or the hypogastric area. External examination of perineal area o Establish normal placement of anal orifice. o Look for: Soiling Fissures Skin tags Normal anal wink in response to touch Rectal examination, with patients cooperation o With functional constipation, desiccated stool is found in the rectal vault. o Megarectum In older children with long-standing constipation: o Chronic rectal distention may efface the internal sphincter along the rectal wall. o Anal canal will feel foreshortened. In children who soil from chronic constipation: o The disorder is sensory. o Tone of the internal sphincter should be normal. o Older child with functional constipation The rectum may be empty if the child has just defecated. Carefully consider the possibility of Hirschsprung disease. o Be alert for extrinsic mass compressing the rectum (rare). o Patulous anus is indicative of a neurologic lesion or sexual abuse. Neurologic examination o Explicitly assess lower extremities for: Tone Strength Symmetry Reflexes o Analyze the patients gait. Examine spine for: o Signs of spina bifida occulta o Dimple o Hair tuft o Palpable vertebral deformity

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Differential Diagnosis

Functional constipation

Despite the large number of possible diagnoses, at least 90% of affected children have functional constipation. Infants o Parental definition of constipation in the first 6 months may be incorrect. o In otherwise healthy breastfed infants: Stool consistency rather than frequency is a critical determinant of constipation.

Straining and grunting (turning deep red) in producing a soft stool of average caliber is normal. Mushy stool once a week requires no intervention. o Functioning rectoanal inhibitory reflex Manometric studies have documented this at birth. Likely represents unsuccessful attempts to coordinate voluntary with involuntary defecation o Treatment is required for the constipated infant who: Strains with production of a desiccated plug of stool followed by loose stool Produces consistently desiccated stool of pebbly consistency Toddlers o History of stool withholding is critical for both diagnostic and therapeutic purposes. o Parents of toddlers are: Usually aware the child is constipated Frequently do not recognize stool withholding o During typical withholding, the child may: Hide quietly Cling to an inanimate object Squeeze buttocks together o Variations of stool-withholding behavior Crouching Dancing or walking on tiptoes Crying out in anticipation of pain o Episodes of withholding: Are misinterpreted by the parents as attempts to defecate Generate great concern in the parent Children o Once the child has attained privacy in the bathroom: Parents are not likely to be involved in toilet routine. Constipation becomes occult. o Incomplete evacuation is common in school-age children; typical scenario: Child goes to the bathroom with regular or increased frequency. Child passes only a small, hard piece of desiccated stool. Child emerges from bathroom not terribly bothered. Parent inquires, Did you go? Child answers, Yes. Thus both parties are happy. Pattern is punctuated episodically by the passage of massive bowel movements. o Many children do not seem terribly bothered by their constipation. o Children are often brought in, not for constipation itself, but for: Soiling Recurrent abdominal pain Blood streaks seen on stool Excessive flatus Anorexia o Pelvic floor dyssynergia in children with stool withholding: Can affect urinary voiding dynamics Predisposes child to enuresis or urinary tract infection Findings that support the diagnosis of functional constipation o Onset after infancy o Presence of stool-withholding behavior o Episodic passage of large-caliber stools o Absence of red flags Failure to thrive (weight loss, poor growth) Vomiting Abdominal distention Persistent anal fissures, perianal disease Persistent blood in stool or guaiac-positive stool Delayed passage of meconium

Weak urinary stream, diurnal enuresis

Anal and rectal disorders

Anal fissure May induce self-perpetuating cycle of withholding, worsening constipation, and reinjury Anterior ectopic anus o Occasionally, the anal orifice is misplaced anteriorly, so that the stool bolus must turn anteriorly at the perineum. o Parents may report seeing a perineal bulge when the infant attempts to defecate. o Consider surgical reconstruction in children who fail to improve with medical therapy. Anal stenosis o Characterized by straining during the production of small-caliber stools o Frequently diagnosed during infancy o Digital examination shows that the anal canal is narrow and not distensible. Rectal duplication Anal trauma (abuse) Extrinsic masses, though rare, may intermittently or partially obstruct the rectum. Rectal duplication cyst Pelvic mass, such as neuroblastoma, presacral teratoma, ovarian tumor, hematocolpos


Hirschsprung disease The most common reason to consider Hirschsprung disease is failure of treatment for functional constipation. Appropriate in early infancy, when functional constipation is unusual and easily treatable In the toddler and the school-age child, more likely to reflect the complexity and duration of intervention required rather than a missed diagnosis of Hirschsprung disease Findings with a very high negative predictive value for Hirschsprung disease: o Almost all children with functional constipation withhold stool in response to the rectoanal inhibitory reflex. o This reflex is absent with Hirschsprung disease. o Hirschsprung disease should be considered in any child with refractory constipation who has had any of the following: Failure to pass meconium in the first 24 hours of life Onset of constipation before 3 months of age Symptoms of intestinal obstruction at any time (distention, pernicious emesis) Lifelong dependence on laxatives, enemas, or mechanical manipulation to initiate defecation History of enterocolitis in early infancy (sometimes misdiagnosed as gastroenteritis) Spinal cord lesions o Affect the second, third, and fourth sacral nerves o Associated with both sensory and motor deficits affecting defecation o Trauma to sacral cord, intraspinal and extraspinal tumors, and congenital malformations can tether the spinal cord. o Consider when constipation is accompanied by abnormalities in bladder function or gait. o Consider when visible abnormalities or palpable deformities of the lumbosacral spine exist. Cerebral palsy Neuromuscular diseases with hypotonia Refractory constipation o Frequently multifactorial and difficult to treat o Prevalent in children with: Cerebral palsy

Muscular dystrophy Generalized hypotonia Pseudo-obstruction syndromes o Characterized by intermittent episodes of functional intestinal obstruction o Affects the neuromuscular function of the colon

Metabolic and endocrine

Hypothyroidism Diabetes insipidus Hypercalcemia Hypokalemia

Medication and toxin related

Antihistamines Anticholinergics Anticonvulsants Opioids Bismuth, aluminum hydroxide Tricyclic antidepressants Iron preparations (not iron-fortified formulas) Plumbism Infant botulism


Celiac disease and cystic fibrosis should be considered in children with: Poor growth in weight or height Recurrent respiratory symptoms Anemia Hypoproteinemia Cows milk allergy o For treatment-resistant chronic constipation, soy milk has been used as a substitute. o In study of 65 children, 44 had a positive response when soy milk replaced cow milk. o Replacing cow milk with soy milk is controversial. Scleroderma Systemic lupus erythematosus

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Laboratory Evaluation
Routine laboratory tests Not indicated in evaluating for functional constipation Tests to consider o Thyroid function tests o Serum calcium o Potassium o Lead o Celiac panel o Sweat test


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Plain abdominal radiographs: Often do not have significant diagnostic value In functional constipation, should show dilated, enlarged rectum In Hirschprung disease, should show empty rectum Can be used: Selectively for confirmation that palpable abdominal mass is a fecal impaction

For a questionable diagnosis in a child unable to cooperate with rectal examination Barium enema: o In functional constipation, should reveal diffusely dilated colon and rectum o In Hirschprung disease, should reveal distal spasm, proximal dilatation Magnetic resonance imaging of lumbosacral spinal cord for: o Hair tufts, lipomas, hemangiomas overlying the lumbosacral spine o Abnormalities of gait o Abnormalities of urination o Absent anal wink o Absent cremaster reflex Diagnostic Procedures
Rectal manometry Functional constipation: rectoanal reflex present Hirschsprung disease: rectoanal reflex absent

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Treatment Approach
Goals of treatment Establish a pattern of soft bowel movements with 3 per week. Wean the child from pharmacotherapy. Have the child and family manage problem on their own with diet and behavioral modification. Involves parental education, laxatives, diet, behavioral modification Considerations o Age of patient o Duration of symptoms and treatment Transient constipation lasting several days o Typically can be managed with 1 to a few days of laxative use and dietary change Functional constipation o Patients are affected for weeks to months before seeking medical attention. o Requires a phased approach and months of treatment o In older children, may require 12 years of laxative therapy

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Specific Treatment


Before the introduction of solids, add undigestible, osmotically active carbohydrates to formula/breast milk. o Dark corn syrup or malt soup extract o Dose: 26 teaspoons per day, divided among several bottles Once juice and infant food are introduced: o Give apple or prune juice and fruits. Infant glycerin suppositories o Can be used at the beginning of therapy to remove a desiccated rectal plug o Should not be the mainstay of therapy because infants can become dependent on rectal stimulation 2 studies have established the efficacy of polyethylene glycol (PEG). Constipated infants should not be treated with mineral oil: risk of pneumonia from aspiration Treat externally visible anal fissures with petroleum jelly.

Toddlers and older children

Functional constipation Highly successful treatment adopted widely by pediatric gastroenterologists with published guidelines

Divided into 3 phases Education and disimpaction Maintenance Weaning o Controlled studies have not documented greater improvement with biofeedback training than with standard treatment regimens. Education o Parents need to know: Constipation frequently engenders withholding. Withholding is self-perpetuating. Toddlers may require several months of laxative that produces soft stools before they abandon withholding. Long-term nonstimulant laxatives are safe, based on innumerable studies. Nonstimulant laxatives that do not engender laxative dependence include: o Mineral oil o Milk of magnesia o PEG o Lactulose Reluctance to medicate children leads to premature discontinuation of therapy. The limited use of senna, an anthraquinone-stimulant laxative, is acceptable as: o Adjunct to an osmotic agent o Rescue therapy for children who have transient relapses Experts discourage the prolonged use of stimulant laxatives (senna, bisacodyl). No proof exists that prolonged use of mineral oil impairs fat-soluble vitamin absorption. o Parents should be instructed to: Ignore withholding events as they would a temper tantrum Talk directly to toddlers and engage them in the therapeutic program. Say, "I want you to push the poo-poo out of your body; dont hold it in. Thats how you will get better, and it will stop hurting. Disimpaction o The goal of disimpaction is to remove all hard-formed stools throughout colon. o Treatment begins with disimpaction for the patient who: Has had months to years of symptoms Has an impaction on examination o For older children: Defer disimpaction until the weekend. Treat with mineral oil to lubricate impacted stool. o Fiber is withheld during the disimpaction phase. o Enemas Once a day for 36 days Simple, effective, and safe (with important caveats) Dose guidelines should be followed. In the rare event of failure to pass stool following an enema, the child needs medical attention. Sodium phosphate enemas are contraindicated in children who: o Weigh < 10 kg o Have cardiac or renal impairment or electrolyte disorders o May have any form of intestinal obstruction o Oral route versus enemas Oral PEG has been used successfully for disimpaction. Choice should be made with the childs and familys input. o Laxative doses Rectal o Hypertonic sodium phosphate enema: 3 mL/kg/dose, once daily via rectum for 1 6 days o Mineral oil enema: 3060 mL, once daily via rectum for 16 days

Oral PEG electrolyte-free: 1.5 g/kg/day, maximum 100 g for 3 days Mineral oil: 30 mL/year of age to maximum 8 oz twice daily for 3 days PEG with electrolytes: 10-40 mL/kg/hr, via nasogastric tube (maximum 2 L/h) until stool effluent clear Maintenance o Follows disimpaction and incorporates laxative use, dietary advice, behavioral modification o Laxative choice Less important than close follow-up for dose adjustment Mineral oil o Contraindicated for children < 2 years or at risk for pulmonary aspiration o Parents should be counseled explicitly never to force a child to take mineral oil. o PEG Cautions for mineral oil also apply for PEG. PEG is an osmotic laxative widely used to treat functional constipation. Polymer of ethylene glycol that is not absorbed or fermented by colonic bacteria Fairly tasteless, water-soluble powder that can be disguised when mixed into a childs drink Pediatric studies have established clinical tolerance, effective dose, and absence of unanticipated or serious adverse effects. In a study comparing low-dose PEG with lactulose, no difference was found between the prevalence of abnormal electrolyte or nutritional parameters. Despite its popularity, it is unclear whether PEG is better and safer than other commonly used laxatives. For severe pulmonary edema from PEG aspiration, bronchoalveolar lavage has been used successfully. o Dietary fiber Addition of fiber is widely advocated as an adjunct. A randomized controlled trial has shown benefits of fiber supplement when prescribed with laxative. Dietary changes that increase childs fiber intake o Whole-grain breads and cereals o Increased fruit and vegetable intake o Behavioral modification Toddlers o Focus on replacing stool-withholding behavior with deliberate attempts to defecate. o Defer toilet-training efforts until the child stops withholding. Older children o Have the child sit on the toilet after meals for 510 minutes to capitalize on the gastrocolic reflex o Reward success by use of a star chart. o Child should be rewarded for the targeted behavior: sitting Physician o Titrate laxative dose to achieve desired effect (soft bowel movement every day) o Work in partnership with the child and parents, who should report to physician frequently Laxative Doses (oral) o PEG electrolyte-free powder: 0.8g1.5g/kg/day o Mineral oil: 13 mL/kg/day o Milk of magnesia: 13 mL/kg/day o Lactulose 10 g/15 mL: 1 mL2 mL/kg/day o Senna syrup 218 mg/5 mL: 1020 mg/kg/dose at bedtime Weaning o Laxative therapy should not be stopped abruptly. o Some toddlers can be weaned after 612 weeks of maintenance treatment. o In older children, weaning may take 612 months.

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Daily laxative dose can be decreased in 1 of 2 ways. Decrease to 75%, 50%, and 25% of initial dose over successive months Give a full dose every second day for 68 weeks, then every third day for another 68 weeks. o Efforts should be redoubled to: Increase fiber intake Foster compliance with behavioral program o Older school-age children should: Be encouraged to practice self-monitoring of frequency and adequacy of bowel movements Have a rescue plan (enema, suppository, or stimulant laxative) for a transient relapse Consider no stool for > 3 days a transient relapse Common reasons for treatment failure of functional constipation o Inadequate disimpaction o Failure to escalate laxative dose to achieve 12 soft stools per day o Premature discontinuation because of the widely held notion that laxatives are addictive o Relying on dietary fiber alone

When to Refer

Abnormal diagnostic studies Findings that are inconsistent with functional constipation o Growth failure o Distention o Vomiting o Bleeding Treatment is complicated by other significant problems. o Behavioral o Emotional o Parenting o Mental health issues o Toileting is the focus of a power struggle. Refer to pediatric gastroenterologist o Infant who is refractory to treatment o Child who is refractory to treatment or cannot wean from laxative therapy after 12 months If Hirschsprung disease is suspected: o Consult with surgeon and radiologist o Decide on initial diagnostic test (rectal biopsy is the gold standard)

When to Admit


Constipation associated with obstruction or enterocolitis Failure of disimpaction as an outpatient

Toddlers and older children Follow-up by phone within 2 days of starting therapy. Ascertain whether the child is still passing hard stools. Titrate laxative dose to induce a daily soft bowel movement. Determine whether disimpaction is complete. o Question to determine whether disimpaction was thorough. Disimpaction failure is a common therapeutic mistake. Initial disimpaction failure undermines successful treatment because maintenancedose laxatives will not penetrate or remove impaction. Failure should prompt a revisit to consider: o Abdominal or rectal examination and/or

Abdominal radiography Children who have extremely hard or treatment-resistant impactions can be admitted for nasogastric administration ofPEG. Remain optimistic and involved, because improvement beyond 12 months of therapy is well documented.

Dietary fiber is believed to have an important role in promoting regular bowel habit. Sufficient fluid intake to prevent dehydration


Medical Decision Support

Evaluation and Treatment of Constipation in Infants and Children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (guideline) North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

AAP Policy Statements

American Academy of Pediatrics, Subcommittee on Chronic Abdominal Pain. Clinical report: Chronic abdominal pain in children.Pediatrics. 2005;115(3):812-815. [PMID:15741394] American Academy of Pediatrics, Subcommittee on Chronic Abdominal Pain. Technical report: Chronic abdominal pain in children. Pediatrics. 2005;115(3):e370e381. [PMID:15741363]

Encopresis Definition Soiling Voluntary or involuntary passage of feces into the clothing Retentive encopresis Leakage of fecal material involuntarily from an impaction Nonretentive encopresis Passage of normal bowel movement into underwear rather than the toilet Lactulose Lactulose Basics Medication Safety Issues Sound-alike/look-alike issues:

Lactulose may be confused with lactose Generic Availability (U.S.) Yes: Excludes crystals for solution Brand Names: U.S. Constulose Enulose Generlac Kristalose Brand Names: Canada Acilac Apo-Lactulose Laxilose PMS-Lactulose Therapeutic Category Ammonium Detoxicant Hyperammonemia Agent Laxative, Miscellaneous Dosing Dosing: Usual Constipation: Oral:

Children: 0.7-2 g/kg/day (1-3 mL/kg/day) in divided doses, maximum daily dose: 40 g/day (60 mL/day) (NASPGHAN, 2006)

Adults: 10-20 g (15-30 mL) daily; may increase to 40 g (60 mL) daily if necessary

Portal systemic encephalopathy, acute treatment: Adults:

Oral: 20-30 g (30-45 mL) every 1 hour to induce rapid laxation; reduce to 20-30 g (30-45 mL) 3-4 times daily after laxation is achieved titrate to produce 2-3 soft stools/day

Rectal administration (retention enema): 200 g (300 mL) diluted with 700 mL of water or NS via rectal balloon catheter; retain for 30-60 minutes may be repeated every 4-6 hours; transition to oral treatment prior to discontinuing rectal administration

Portal systemic encephalopathy, prevention: Oral:

Infants: 1.7-6.7 g/day (2.5-10 mL/day) in divided doses; adjust dosage to produce 2-3 stools/day

Children: 26.7-60 g/day (40-90 mL/day) in divided doses; adjust dosage to produce 2-3 stools/day

Adults: 20-30 g (30-45 mL) 3-4 times daily; adjust dose every 1-2 days to produce 2-3 soft stools/day Dosage Forms Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Crystals for solution, oral:

Kristalose: 10 g/packet (30s); 20 g/packet (30s)

Solution, oral: 10 g/15 mL (15 mL, 30 mL, 237 mL, 473 mL, 500 mL, 946 mL, 1892 mL)

Constulose: 10 g/15 mL (237 mL [DSC], 946 mL)

Enulose: 10 g/15 mL (473 mL)

Solution, oral/rectal: 10 g/15 mL (237 mL, 473 mL, 946 mL)

Generlac: 10 g/15 mL (473 mL, 1892 mL) Usage Use Prevention and treatment of portal-systemic encephalopathy (PSE) (FDA approved in infants, children, adolescents, and adults); treatment of constipation (FDA approved in adults) Administration Oral: Administer with juice, milk, or water; dissolve crystals in 4 ounces of water or juice

Rectal: Mix with water or normal saline; administer as retention enema using a rectal balloon catheter; retain for 30-60 minutes Stability Store at room temperature. Solution: Do not freeze. Protect from light. Discard solution if cloudy or very dark. Prolonged exposure to cold temperatures will cause thickening which will return to normal upon warming to room temperature. Contraindications Hypersensitivity to lactulose or any component; patients requiring low galactose diet Warnings During proctoscopy or colonoscopy procedures involving electrocautery, a theoretical risk of reaction between hydrogen gas accumulation and electrical spark may exist; thorough bowel cleansing with a non-fermentable solution is recommended. Precautions Use with caution in patients with diabetes mellitus (contains galactose and lactose); do not use with other laxatives especially when initiating PSE treatment as increased loose stools may falsely suggest adequate lactulose dosage. Electrolyte imbalance may occur when lactulose is used >6 months or in

patients predisposed to electrolyte abnormalities; hepatic disease may predispose patients to electrolyte imbalance; infants receiving lactulose may develop hyponatremia and dehydration. Adverse Reactions Endocrine & metabolic: Dehydration, hypernatremia, hypokalemia

Gastrointestinal: Abdominal discomfort, abdominal distention, belching, cramping, diarrhea (excessive dose), flatulence, nausea, vomiting Interactions Drug Interactions There are no known significant interactions. Drug Interactions: Metabolism/Transport Effects None known. Food Interactions Contraindicated in patients on galactose-restricted diet Pregnancy & Lactation Pregnancy Risk Factor B Pregnancy Considerations Adverse events have not been observed in animal reproduction studies. Lactation Excretion in breast milk unknown/use caution Pharmacology Mechanism of Action The bacterial degradation of lactulose resulting in an acidic pH inhibits the diffusion of NH3 into the blood by causing the conversion of NH3 to NH4+; also enhances the diffusion of NH3 from the blood into the gut where conversion to NH4+ occurs; produces an osmotic effect in the colon with resultant distention promoting peristalsis and elimination of NH4+ from the body

Pharmacodynamics Onset of action:

Constipation: Up to 24-48 hours to produce a normal bowel movement

Encephalopathy: At least 24-48 hours Pharmacokinetics (Adult data unless noted) Absorption: Oral: Not absorbed appreciably

Metabolism: By colonic flora to lactic acid and acetic acid

Elimination: Primarily in feces; urine (3%) Monitoring Serum ammonia, serum electrolytes, fluid status, stool output Additional Information Upon discontinuation of therapy, allow 24-48 hours for resumption of normal bowel movements