Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Gastrointestinal Symptoms


Digestion, of all the bodily functions, is the one which exercises the greatest influence on the mental state of an individual. —Jean-Anthelme Brillat-Savarin

Palliative care no longer means helping children die well, it means helping children and their families to live well, and then, when the time is certain, to help them die gently. —Mattie Stepanek

A 16-year-old girl with cystic fibrosis and advanced but stable lung disease was hospitalized with severe abdominal pain, nausea, and anorexia following viral gastroenteritis. There was an initial belief that she may have a partial bowel obstruction but this was ruled out after multiple investigations failed to show any significant organic factors. She adamantly denied anxiety or depressive symptoms.

The gastrointestinal symptoms did not improve with standard psychological and pharmacologic strategies, and her lung function began to deteriorate further secondary to weight loss and immobility. A family meeting involving the psychosocial team, the teen, and her parents provided a forum for her parents to discuss their spiritual beliefs and the teen's acceptance that she would die from her condition at some stage. This was distressing for the teen to hear and allowed her to talk about her own anxieties about death, her fear that her symptoms represented a terminal illness, and that her death would be sudden and unexpected and that her family could not be present because of that. She had been reluctant to discuss these matters with her parents as she believed they would be disappointed in her.

These revelations opened the way for her primary pediatrician to discuss with her the likely modes of death from cystic fibrosis, and the expectation that her death was not imminent given good nutrition and mobilization. The pediatrician also promised to talk openly and honestly with her when her lung function declined to the point that her death was near. Within several days the young woman was eating well, mobilizing, communicating more openly with her family, and her pain levels were manageable. She lived with a good quality of life for an additional 14 months before dying at home with her family present.

This vignette highlights a number of important concepts of pediatric palliative care and pediatric medicine in general. Arguably, the most important of these is the existence of a strong, inextricable link between the physical and the psychological, or the mind-body link. This link brings into sharp relief the need to work in an interdisciplinary fashion, as no one person and no one discipline has the full skill set to adequately address the needs of a child, and his or her family, with a life-threatening condition.

Adherence to a purely mechanistic and/or biological approach to care provides some degree of success and, in controlling troublesome symptoms, can open the door to address the wider emotional, psychosocial, and spiritual issues that are present. Not addressing these appropriately ultimately means lost opportunities and inferior care. In this example, symptoms were not amenable to a pharmacologic approach and should stand as a warning that properly investigated and treated symptoms that remain uncontrolled indicates the need to deal with an underlying psychological, emotional, and/or spiritual issue.

A well-functioning interdisciplinary team is critical to the management of gastrointestinal symptoms in pediatric palliative care. The nature of the interdisciplinary work in a specific team is often shaped by the members of the team and the range of disciplines included. In addition to the holistic child and family focused skill set expected of all team members, there are some particular skills that are more specific to nurses, medical practitioners, or psychosocial clinicians.

Nurses often provide overall case management that incorporates ongoing symptom assessment, medication management, and psychosocial care, but they also have unique skills in the assessment and provision of physical care and comfort to the dying child. Some of these skills include providing and/or teaching family members developmentally appropriate strategies for feeding, toileting, wound care, line management, medication administration, and positioning and pressure area care.

Physicians have particular skills and training in diagnostic assessment, particularly where there are complex symptoms, in palliative treatment and/or management planning, and in pharmacologic interventions.

Psychosocial or mental health clinicians may come from a variety of disciplines including psychology, psychotherapy, social work, child life, chaplaincy, and psychiatry. Specific skills include the assessment of more complex mental health issues for children and family members and of challenging family interaction or communication difficulties. They can provide psychotherapeutic input such as play therapy, cognitive behavioral therapies for such things as anxiety, depression, pain, nausea, hypnosis training, focused family and couple work, and in some instances, systems interventions where communication difficulties are present among teams involved in the child's care.

Gastrointestinal symptoms and distress are relatively common in children and are not limited to those receiving palliative care. Tummy-aches and vomiting are integral to the childhood portrayed by Shakespeare with his ‘mewling and puking’ infant, and the nursery rhymes and songs of childhood where ‘Miss Polly had a dolly that was sick, sick, sick’ and on the good ship Lolly-pop where ‘if you eat too much, oh, oh, you'll awake with a tummy-ache.’ As many as 30% of otherwise healthy children will experience recurrent abdominal pain during childhood, one in six adolescents report functional gastrointestinal symptoms consistent with irritable bowel syndrome (IBS), and abdominal discomfort maybe the primary presenting symptoms for the child with anxiety and emotional difficulties.

Gastrointestinal symptoms are prominent among children receiving palliative care. Six studies examining the prevalence of distressing symptoms in a total of 592 children with malignant and non-malignant diseases reveal that the majority of dying children experience pain, 53% to 92%, and fatigue, 52% to 97%, during their end-of-life period. In addition, a large percentage suffer from gastrointestinal symptoms such as vomiting and/or nausea, 40% to 63%, constipation, 27% to 59%, and diarrhea, 21% to 40%.

Many of these children will have previously experienced abdominal pain, nausea and vomiting, anorexia, and disturbed bowel function in association with their primary disease, or as a consequence of treatment and treatment complications. The result is that they and their parents may be particularly anxious and sensitized to any recurrence of symptoms, as this may be perceived as a heralding event to deterioration and the onset of the final stages of the child's illness. In addition, any alteration or loss of the normal bodily rhythms of eating and toileting is disquieting for families; the inability to feed and nourish their child may symbolize failure of the most fundamental parenting role, and loss of bowel control may be humiliating and seem like the final insult for a young person with a life-threatening illness. For these reasons alone, the evaluation and management of the many potential contributors to gastrointestinal distress is challenging and requires a holistic approach.

This chapter aims to provide treatment algorithms for individual gastrointestinal symptoms as originally proposed in 2000. The evidence for any recommendations made is often poor due to the lack of randomized controlled trials (RCTs) in pediatric palliative care and, unfortunately, pediatrics continues to be hampered by the common, unacceptable problem of many medications not being approved for use in children or for the specified indication resulting in off-label use.

Nausea and Vomiting

Nausea and vomiting is one of the most distressing symptoms for ill children and their caregivers. Gastrointestinal, central nervous system (CNS), metabolic, pharmacologic, and psychological factors may all contribute, and prolonged episodes of nausea and vomiting may themselves contribute to the development of anticipatory nausea and conditioned vomiting. Treatment approaches are best based on the presumed, following careful assessment, underlying pathophysiology and management should include integrative therapies, such as cognitive behavioral therapies, aromatherapy, and acupressure, where appropriate.

Pathophysiology

Vomiting is controlled by two distinct brain centers, the vomiting center and the chemoreceptor trigger zone (CTZ). Both are located in the medulla oblongata with the CTZ lying outside the blood-brain barrier in the area postrema at the floor of the fourth ventricle, while the vomiting center is located inside the blood-brain barrier.

Excitation of the vomiting center results in nausea and vomiting and the reflex may result from the following input:

  • Direct activation of the CTZ. Responds to metabolic products or medications in the blood or cerebrospinal fluid.

    • Dopamine type 2 (D 2 )-receptors in the area postrema are stimulated by emetogenic substances such as calcium, uremia products, opioids, and digoxin.

    • 5-Hydroxytryptamine (5HT) 3 -receptors, also located at the area postrema, respond to many cancer-directed chemotherapy drugs and uremia.

  • Stimulation via the vestibular apparatus.

    • Muscarinic acetylcholine (ACh m ).

    • Histamine (H 1 ) excitatory receptors.

  • Gut wall and vagal and/or splanchnic afferents. Both carry 5HT 3 -receptors, the former also has 5HT 4 and D 2 -receptors.

    • All play an important emetic role and are activated by distention in the gut lumen, abdominal radiotherapy, and chemotherapy when serotonin (5HT) is produced by the enterochromaffin cells lining the lumen epithelium.

    • Peripheral or central afferents. Emetogenic stimuli reaches the central nervous system via afferent pathways with the nucleus tractus solitarii probably playing a coordinating role.

    • Sensory stimuli such as smells that have previously been associated with episodes of vomiting can become triggers for anticipatory nausea and so-called conditioned vomiting.

Toxins commonly associated with nausea and vomiting during the pediatric end-of-life period include medications such as chemotherapeutic agents, antibiotics, and opioids, and metabolic byproducts of uremia or hepatic failure.

The majority of receptors in the vomiting center and CTZ are excitatory, that is, they induce nausea and vomiting with stimulation. An important exception is the presence of the μ-opioid receptor in the vomiting center. Opioids seem to have a dose-dependent interaction on emesis. At standard doses, opioids may cause nausea by stimulating D 2 -receptors in the area postrema but at high doses opioids are often not emetic. This is postulated to be due to an antiemetic or inhibitory effect at the μ-opioid receptor in the vomiting center.

Opioid-Induced Nausea

Although individual patients may tolerate one opioid better than another, data suggest that prevalence of these side effects differ greatly among the commonly used opioids. Children usually develop tolerance to nausea, however this may take days to occur. From experience the single most helpful approach to opioid-induced nausea in the Minneapolis pediatric pain and palliative care patients represents a rotation or a switch to another opioid at an equianalgesic dose.

Alternatively, low-dose naloxone infusions, at 0.25–1 mcg/kg/h, can reduce the frequency and severity of nausea without antagonizing analgesia in children who receive opioids. Infusion rates used are several-fold lower than infusion rates typically used to produce measurable reversal of analgesia or respiratory depression.

If neither an opioid rotation nor low-dose naloxone infusion are effective or feasible in the disease trajectory, then the addition of a dopamine (D 2 )-receptor antagonists such as metoclopramide and antiemetics of other classes should be considered, see later in this chapter.

Treatment algorithm

Step 1: Evaluation and Assessment

Every child suffering from nausea and/or vomiting in palliative care needs to be thoroughly evaluated by taking a careful history and performing a focused clinical examination. Questions of clinical importance include possible correlation with eating, medication administration, and association with other symptoms such as pain or sensory stimuli. Undertreated pain can cause nausea and vomiting. Other considerations are the presence or absence of raised intracranial pressure, sub-ileus, constipation, or seizures.

Step 2: Treatment of Underlying Causes

Any consideration to treat an underlying cause needs to take into account each child's situation with a key element of these deliberations being the maintenance or improvement of the child's quality of life. Common pathophysiologies are constipation, reflux, sub-ileus, infections such as gastroenteritis, metabolic disorders including hypercalcemia and renal failure, seizure, and anxiety. Drug adverse effects are common and include side effects to antibiotics, anticholinergics, corticosteroids, non-steroidal anti-inflammatory drugs, opioids, palliative chemotherapy, and tricyclic antidepressants.

Step 3: Implement Integrative and Supportive Therapies

The combination of supportive and integrative modalities with pharmacologic management should be seen as a gold standard to any pain and symptom management approach in the twenty-first century. Integrative and supportive approaches include the provision of small meals chosen by the child, frequently offering favorite drinks, good oral care, and the avoidance of discomforting smells.

Management of anxiety for the child and his or her family is paramount and should start with careful explanation of the likely factors contributing to the symptoms. A number of therapeutic techniques can be used to help the child to relax, feel calmer, and have a greater sense of control. These include cognitive behavioral strategies such as simple relaxation exercises, controlled breathing, and focusing on positive self messages and imagery. Younger children may need a parent to cue them and help them with guided imagery and stories, while older children can be taught self-hypnosis to manage symptoms. Pleasant masking aromas of the child's choosing can also be used if there are particular odors that trigger nausea. Scheduling enjoyable distracting activities including music, or acupressure or acupuncture may also be useful for some children.

An 11-year-old boy with a previous history of severe chemotherapy-associated nausea and vomiting was troubled by persistent nausea during the palliative phase of management for relapsed osteosarcoma. Although no longer receiving chemotherapy, the smell of the hospital antiseptic and the smell of his overnight enteral feed triggered bouts of intense nausea. Working with the team psychologist, he was able to use a combination of muscle relaxation, calm breathing and thinking about his favorite television program hero to reduce his nausea and associated anxiety. He also found that the smell of citrus and eucalyptus oils helped mask the hospital smell during clinic visits, and at his nighttime feed at home.

Step 4: Pharmacology

The selection of an antiemetic for treatment of nausea and/or vomiting requires a rational approach based on the assessed pathophysiology (see previous text) and, because both nausea and vomiting can have multiple etiologies in any individual, initially directed at the major cause. In the event of a single agent being ineffective, then a combination of antiemetics, where each targets different receptors, should be considered. Several randomized controlled trials (RCTs) exist only in children with cancer and postoperative nausea, and may not be applicable for children with non-malignant conditions in palliative care. However, the rational approach of first targeting the assessed major etiology followed by the introduction of an agent with a different receptor action profile, if needed, should be seen as good practice.

5-HT 3 -Receptor Antagonists

Several RCTs showed that the serotonin (5-hydroxytryptamine-3) antagonist ondansetron (Zofran) provides a good antiemetic effect in children with cancer after chemotherapy administration or bone marrow transplant, compared with placebo and other antiemetics such as metoclopramide plus dexamethasone or metoclopramide plus diphenhydramine. Other 5-HT 3 antagonists, such as tropisetron (Navoban) and granisetron (Kyrtec) show a similar effect.

A common adverse effect of this class is constipation. They may also cause headaches, and nausea at higher doses, especially when administered above the recommended doses. Anecdotal experience also suggests 5-HT 3 -receptor antagonists are effective for nausea and vomiting in children with non-malignant palliative conditions.

D 2 -Receptor Antagonists

Dopamine 2 -receptor antagonists such as metoclopramide (Reglan) and haloperidol (Haldol) are prokinetic and have been clinically effective in treating nausea and vomiting in pediatric palliative and hospice care. Stress, anxiety, and nausea via peripheral dopaminergic receptors at the plexus myentericus may cause a slowing of gastrointestinal passage, the so-called dopamine break. This effect is antagonized by metoclopramide (Reglan) and domperidone (Motilium). Other D 2 -receptor antagonists may have a similar effect.

They may, however, be underused due to an overemphasis on possible extrapyramidal reactions. Metoclopramide has been associated with a dyskinetic syndrome and reported to occur with an incidence of 1:5000 in teenagers. Any such reaction can be treated with either a centrally acting antihistamine, such as diphenhydramine (Benadryl), or central anticholinergic, such as benztropine. This concern extends to a lesser extent to phenothiazine derivates (psychotropics) such as haloperidol (Haldol), prochlorperazine (Compazine), and chlorpromazine (Thorazine). Chlorpromazine and prochlorperazine are also H 1 - and ACh m - receptor antagonists.

Domperidone does not cross the blood-brain barrier and therefore does not cause extrapyramidal side effects. The intravenous form of domperidone was discontinued following reports of cardiovascular adverse effects.

Prokinetics should not be administered concurrently with antimuscarinic agents, such as diphenhydramine or scopolamine, as these block the final common pathway for prokinetic agents. The concurrent administration of diphenhydramine and metoclopramide to prevent a dyskinetic syndrome, as practiced in some centers, will therefore result in the loss of metoclopramide's prokinetic effect, however not of its antiemetic effect. The concurrent intravenous administration with 5-HT 3 -receptor antagonists increases the risk of cardiac arrhythmia. Droperidol (Inapsine), a butyrophenone neuroleptic similar to haloperidol, can no longer be recommended because of the risk of QT prolongation.

H 1 - and ACh m - Receptor Antagonists

Histamine-1 and muscarinic acetylcholin receptor antagonists are effective antiemetics in daily clinical practice though there are no pediatric RCTs. These medications have an astounding regional preference without any head-to-head comparison. The first-generation antihistamine diphenhydramine (Benadryl) has a significant anticholinergic, especially sedating, side effect and is hardly used as a first-line medication outside North America. Promethazine (Phenergan), commonly used in Australia, is similarly sedating. In central Europe the preferred pediatric antiemetic is dimenhydrinate (Dramamine), which in clinical practice rarely causes over-sedation. The most commonly used antinausea drug in the UK on the other hand is cyclizine.

Scopolamine, an ACh m, but not H 1 , receptor antagonist with stronger anticholinergic side effects than dimenhydrinate or cyclizine, can also be administered as a transdermal patch.

Medications that also have D 2 -receptor antagonistic properties include chlorpromazine, prochlorperazine, and levome-promazine. The latter, in our experience, is particularly helpful in refractorary nausea in pediatric palliative care and is not available in the United States.

NK 1 -Receptor Antagonists

Aprepitant (Emend), a neurokinin-1 receptor antagonist, possesses antidepressant, anxiolytic, and antiemetic properties. NK 1 receptors can be found in the central and peripheral nervous system, as well as the gastrointestinal tract. RCTs indicated it to be superior to ondansetron 24 to 48 hours post-surgery when given as a single pre-operative dose but, in general, pediatric data is scarce. One RCT (n = 46) in adolescents with chemotherapy-induced nausea and vomiting showed the combination of aprepitant (125 mg IV TID), dexamethasone, and ondansetron to be superior to dexamethasone and ondansetron alone.

Cannabinoids

The activation of the endocannabinoid system suppresses behavioral responses to acute and persistant noxious stimulation, and d -9-tetrahydrocannabinol (THC) has been shown to have an antiemetic effect. THC can also stimulate appetite in addition to minimizing nausea.

Two types of cannabinoid receptors have been identified, CB 1 and CB 2 . CB 1 receptors are found in the central nervous system, including periaqueductal gray, rostral ventro-medial medulla and in peripheral neurons, where activation produces a suppression in intestinal neurotransmitter release. Dronabinol and nabilone do not fully replicate the effect of total cannabis preparations but a meta-analysis of 30 RCTs ( n = 1366 patients) showed cannabinoids to be effective for controlling chemotherapy-related sickness in adults. Adverse effects included dizziness, dysphoria, depression, hallucinations, paranoia, and arterial hypotension.

Corticosteroids

Nausea caused by raised intracranial pressure secondary to a brain tumor may show dramatic short- to medium-term improvement with corticosteroid administration. Agents such as dexamethasone are thought to act by reducing the peri-tumor edema. In addition, corticosteroids inhibit prostaglandin synthesis, which may also play an antiemetic role. Because of the significant side effect profile, including mood swings and excessive weight gain, associated with this class of drugs use in palliative care is controversial.

Benzodiazepines

Low-dose benzodiazepines, such as midazolam, lorazepam, or diazepam, can be a part of an effective antiemetic drug treatment in pediatric palliative care. However, there is only limited pediatric data with RCTs showing effectiveness for postoperative nausea and chemotherapy-induced nausea.

Propofol

Propofol possesses antiemetic properties at subhypnotic doses. The mechanism of action of this short-acting hypnotic and general anesthetic is not well defined and possibly includes potentiation of GABA-A receptor activity, sodium channel blocking activity, and activation of the endocannabinoid system. One adult case study reports successful nausea management in palliative cancer care at 0.6–1 mg/kg/h intravenously. Little pediatric data is published but the experience of the program in Minnesota with low-dose propofol in 12 children and teenagers points to it having an important role in managing refractory pain and nausea at the end-of-life when other agents fail ( Table 33–1 ).

TABLE 33-1
Medications in the Treatment of Nausea and Vomiting
Receptor activity Medication Dose Route of administration Comments and side effects
5-HT 3 -receptor antagonists Ondansetron (Zofran) 0.1-0.2 mg/kg Q6-8h; max. 4-8 mg/dose IV, PO, SL Induces nausea and constipation at higher doses
Granisetron (Kyrtec) 0.01-0.05 mg/kg Q8h; max.3 mg/dose IV, PO, transdermal patch Induces nausea and constipation at higher doses
Dopamine(D 2 )- receptor antagonists Metoclopramide (Reglan) 0.15-0.3 mg/kg (max. 10-15 mg) Q6h IV, PO, PR Extrapyramidal side effect. Prokinetics not to be given concurrently with antimuscarinics
Haloperidol (Haldol) 0.01-0.1 mg/kg Q12h (slowly titrated to max. of 1-2 mg/kg, max. 100 mg/dose) IV, PO Class: Butyrophenone; extrapyramidal side effect
Domperidone 0.2-0.4 mg/kg Q4-8h; max. 10 mg PO, PR Does not cross blood-brain barrier, and no extrapyramidal side effects
Histamine (H 1 )/muscarinic acetylcholine (ACh m ) receptor antagonists Dimenhydrinate (Dramamine) 1-2 mg/kg Q8h IV; 2-5 mg/kg Q6-12h IV, PO, PR Anticholinergic side effects including constipation, sedation
Cyclizine 1 mg mg/kg Q8h PO, IV Anticholinergic side effects
Diphenhydramine (Benadryl) 0.5-1 mg/kg Q6h (max. 50mg) PO, IV Anticholinergic side effects, including significant sedation
Promethazine (Phenergen) 0.2-0.5 mg/kg Q6h IV, PO Anticholinergic side effects, including significant sedation
Scopolamine (Transderm Scop) 0.01 mg mg/kg Q6h IV; Patch: 0.33 mg/24h or 0.5 mg/24h: > 10 years Q72h IV, transdermal Antimuscarinic, not an antihistamine. Anticholinergic side effects
Dopamine(D 2 )- and histamine (H 1 )/muscarinic acetylcholine (ACh m ) receptor antagonists Chlorpromazine (Thorazine) PO, PR: 0.5-2 mg/kg; IV: 0.25-1 mg/kg slow infusion PO, PR, IV Phenothiazine: psychotropic effect. Extrapyramidal and anticholinergic side effects, agranulocytosis
Prochlorperazine (Compazine) 0.1-0.2 mg/kg Q8h PO Phenothiazine: psychotropic effect. Extrapyramidal and anticholinergic side effects, agranulocytosis
Neurokinin-1 receptor antagonists Aprepitant (Emend) > 12 years preoperative dose 40 mg (not per kg) once 125 mg (not per kg once, then 80 mg once per day during chemotherapy) PO Chemotherapy-associated nausea. Side effects: Constipation, headaches, fatigue, sinus tachycardia
Cannabinoid (CB 1 ) receptor agonist Nabilone (Cesamet) Adult dose: 1-2 mg BID PO May stimulate appetite Side effects: dizziness, dysphoria, hallucinations, arterial hypotension
Dronabinol (Marinol) 5 mg/m 2 Q2-4h, max. 4-6 doses/day PO Dizziness, dysphoria, hallucinations, arterial hypotension

Summary

A multimodal approach to controlling nausea and/or vomiting should be directed toward the most likely assessed pathophysiology. Uni-modal approaches including pharma-cology alone have a high risk of treatment failure in pediatric palliative care. The evidence does not allow for a step-by-step approach when the underlying mechanism remains unclear but clinical experience would suggest the following pharmacologic approach can work well. The palliative care teams in Minneapolis as well as in Auckland usually schedule a single medication and add another scheduled agent acting on a different receptor group if ineffective, not infrequently requiring two, three, or even four scheduled around-the-clock antiemetics.

First Line

  • 1.

    5-HT 3 -receptor antagonist, such as ondansetron; and/or

  • 2.

    D 2 -receptor antagonist, such as metoclopramide; and/or

  • 3.

    H 1 & ACh m -receptor antagonist, such as dimenhydrinate

Second Line

  • 1.

    Consider adding corticosteroid, such as dexamethasone as a short-term pulse.

  • 2.

    Add a low-dose benzodiazepine such as midazolam.

  • 3.

    Substitute first-line drugs of same class, such as rotation to granisetron, haloperidol, diphenhydramine.

  • 4.

    Consider substituting phenothiazine, such as chlorpromazine, for both antihistamine and dopamine receptor antagonist.

Third Line

  • 1.

    Consider aprepitant.

  • 2.

    Add cannabis, such as dronabinol.

  • 3.

    Consider low-dose propofol.

Considerations in the setting of bowel obstruction include octreotrid (see following text).

Constipation

Hardly any other topic in palliative care provokes more discussion than the treatment of constipation. This could be in part due to it being such a common symptom, at 27% to 59% in children at the end of life, that healthcare workers feel sufficiently knowledgeable about its treatment to have an opinion. Yet, constipation can be quite difficult to manage, resulting in a significant impact on the child and their family. This makes prevention of constipation of utmost importance in pediatric palliative care.

Normal stool frequency varies in children from three times per day to once every 3 days, and in the case of a breast-fed infant, up to once every 2 weeks. Common reasons for constipation in pediatric palliative care include dietary changes, a decrease in fluid and/or food intake, and a decrease in mobility and activity as colon peristalsis is, in part, stimulated by activity.

Chronic constipation is common in children with underlying neurologic impairments related to longstanding poor tone and immobility, while in children with cancer intra-abdominal tumors can cause direct compression of the gut or spinal cord compression.

Treatment algorithm

Step 1: Evaluation and assessment

Constipation commonly results in abdominal pain, bloating, flatulence, nausea and vomiting. The presence of sloppy, foul-smelling feces and soiling should be an alert to the presence of constipation with overflow incontinence.

As with the evaluation of any symptom, a thorough history is required and focused examination must be completed. Adolescents in particular may not volunteer important information about changes in bowel habit because of embarrassment, so it is important to tactfully check for specific changes.

Examination includes a rectal examination, using the small finger for small children, to evaluate whether the rectum contains stool and what consistency it is. There are a number of circumstances where this part of the examination may not be advisable, particularly when the child is neutropenic or thrombocytopenic. The exam can be helpful in ruling out local pain from anal fissures or hemorrhoids as a cause for constipation.

Attention needs to be paid to warning signs indicating neurologic compromise, such as: lower extremity motor weakness, paresthesisias, urinary retention, and fecal incontinence.

If the diagnosis is in question, then an abdominal radiograph or an ultrasound may be helpful in the assessment of stool content and to rule out an obstruction.

Step 2: Treatment of Underlying Causes

Underlying causes of constipation should be treated, if possible. In addition to the previously mentioned common reasons for constipation, consideration should be given to management of anorexia (see following text), weakness, decreased abdominal muscle tone, inconvenient toilet access, poor posture, and psychological factors such as depression. More specific pathologies to consider are hypothyroidism, hypokalemia, hypercalcemia, bowel obstruction (see later text), and adverse effects of medication.

Step 3: Implement Integrative and Supportive Therapies

Whenever possible, integrative and supportive approaches need to be implemented to manage a child's constipation, and include:

  • The establishment of a regular bowel routine should be supported: The strongest propulsive contractions occur postprandial, especially after breakfast. Access to a toilet or potty, with privacy for older children, daily at this time may be beneficial.

  • Encourage the increase of activity, which may include the help of physical therapy or child life specialist, outside of a bed if possible.

  • Increase fluid intake of the child's favorite drinks.

  • Increase dietary fiber. Prune juice is often well liked.

  • Consider abdominal massage in clockwise fashion.

  • Carefully review medications and their constipating side effects, including opioids (see following text), tricyclic antidepressants, phenothiazines, diuretics, antihistamines and/or anticholinergics, and iron supplements. Self-hypnosis, biofeedback and cognitive-behavioral therapy may be effective in children with neurogenic bowel.

Step 4: Pharmacologic Management

A stool softener without a stimulant is mush without push.

A rational approach usually seems to include the scheduled administration of a stool softener and, if ineffective, the addition of a stimulant. However, with distressing constipation, especially when the rectal exam reveals hard stool in the ampulla in conjunction with abdominal pain, children may have to be unplugged first with the use of a rectal suppository or an enema. A manual evacuation would be usually reserved for adult-sized teenagers, if the former approaches fail.

Stool Softener

Stool softeners include liquid osmotic laxatives, such as lactulose, sorbitol, and polyethylene glycol, which draw water into the bowel by osmotic effect and surfactant laxatives including docusate sodium, which increase water penetration.

Outside the United States, the most commonly used stool softener in pediatrics appears to be the sugar lactulose, a combination of galactose and fructose (Enulose). Lactulose does not affect the management of diabetes mellitus. In North America, polyethylene glycol (Miralax) is frequently used instead, and has also shown to be effective and safe. Lactulose's advantage over polyethylene glycol is the much smaller volume, which is beneficial in the pediatric palliative care setting, where children often have trouble taking medication orally. All laxatives, including stool softeners, may cause abdominal pain and meteorism.

Stimulant laxatives

Children with a full rectum containing soft feces, or those for whom stool softeners were ineffective as a single approach, may be treated with a stimulant laxative such as senna or bisacodyl, to stimulate bowel motility. These medications act by stimulation of the myenteric plexus. However, stimulants alone can be dangerous when there is obstruction or impaction.

Contrary to conventional wisdom, that stool softeners should be administered with stimulants, one recent RCT ( n = 60 adults) treating opioid-induced constipation, showed that sennosides alone were superior than sennosides plus docusate.

Of note, the brand name Dulcolax in the United States refers to three medications: the stimulant bisacodyl and the stool softeners docusate sodium or polyethylene glycol, supporting the notion of avoiding brand names in medication.

Prokinetics

If gastrointestinal hypoactivity is a presumed pathophysiology, then prokinetics such as low-dose metoclopramide or low-dose erythromycin, 5 mg/kg QID, may be considered.

Suppositories and Enemas

As mentioned previously, in cases of severe impaction a child may need to receive a rectal suppository or enema for relief. Some young people are acutely embarrassed and resistant to even the thought of using a suppository or enema. This may be a particular issue in early adolescence when bodily concerns, increased self-consciousness, and concerns about privacy are prominent. Careful explanation of the choices and reasons for use of enemas or suppositories is needed, along with negotiation about who the young person would feel most comfortable with to assist them. In cancer patients with neutropenia and/or thrombocytopenia, the rectal administration needs to be weighed against the risk of infection and/or bleeding. Glycerine suppositories promote defecation by softening and lubricating the mass as well as stimulating defecation. The Pain & Palliative Care team in Minneapolis has gathered good experience with the polyphenolic bisacodyl suppositories, which act principally by promoting colonic peristalsis.

Enemas may be required if the constipation is unresponsive to combined scheduled stool softeners and stimulant laxatives. Adult data shows that sodium phosphate/sodium biphosphate enemas, or saline rectal laxatives, and docusate sodium/glycerin mini-enemas, or surfactant rectal laxatives, are equal in efficacy. However, the latter is usually preferred in pediatrics because of its much smaller enema volume of 2.5–5 mL compared with 130 mL.

If a manual evacuation is considered, adequate analgesia and sedation would be the expected standard of care.

Opioid-Induced Constipation

The mantra in adult medicine “the hand who writes the opioids without writing for laxatives is the hand who disimpacts the patient's bowel” should serve at least as a warning in pediatrics. Unless diarrhea or other specific contraindication is present, laxatives should be prescribed routinely whenever more than one opioid dose per day is administered. The previous principles of a stool softener, possibly complemented with a stimulant and/or suppository, holds true as well.

Opioid-Antagonists

The administration of opioid-antagonists has shown to be rather effective in the management of opioid-induced constipation in adults. Pediatric studies have not yet been published.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here