Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute symptoms

1st line – dietary modification

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ACUTE
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acute symptoms
1st line – 

dietary modification

All patients should be offered dietary advice. Patients may be intolerant of certain types of foods such as dairy products and red meat, which can be avoided. Other dietary interventions that could help are: consuming small, frequent (4-6/day) meals; consuming a diet low in insoluble fiber (a diet high in insoluble fiber slows down gastric emptying and promotes the formation of bezoars); consuming a low-fat diet; consuming a small-particle-size diet, which could improve symptoms of nausea/vomiting, postprandial fullness, bloating, and regurgitation; changing the diet to a high-calorie liquid diet or liquidized/blended meals.[35][60]​​[82][83]​​​​

Consider – prokinetic agent

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ACUTE
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acute symptoms
Consider – 

prokinetic agent

Treatment recommended for SOME patients in selected patient group

A prokinetic should be commenced in patients who continue to have symptoms of gastroparesis despite dietary modification. This may need to be continued as ongoing prophylactic treatment.

Prokinetics increase antral contractility, correct gastric dysrhythmias, and improve antroduodenal coordination. The main classes of prokinetics used are dopamine receptor antagonists (e.g., metoclopramide, domperidone) or motilin receptor agonists (e.g., erythromycin).

Metoclopramide is the only approved drug for the treatment of diabetic gastroparesis in the US, and is the first-line pharmacologic therapy.[1]​ It is known to improve gastrointestinal symptoms and gastric emptying. It also has antiemetic properties.[84][85]​​​​​​ There is a risk of parkinsonism and tardive dyskinesia, especially with high doses and prolonged use. Therefore, the European Medicines Agency recommends that oral and parenteral formulations should be used for up to 5 days only in order to minimize the risk of neurologic and other adverse effects, and its use in the long-term treatment of gastroparesis is no longer recommended.[86] The Food and Drug Administration (FDA) has placed a warning on metoclopramide because of the risk of extrapyramidal adverse effects and potentially irreversible tardive dyskinesia (which has been reported in a small percentage of cases), but recommends that it can be used for up to 12 weeks.[1][68]​​​​ It is recommended that 10-day interruptions every 12 weeks (drug holidays) should be instigated. During these drug holidays, patients should be advised to stick to a liquid diet. Rescue antiemetics or short-term treatment with erythromycin can be used for symptom control if needed.[87]​ Other adverse effects of metoclopramide may include drowsiness and fatigue. Up to 30% of patients may not be able to tolerate metoclopramide due to its adverse effects, which are generally more common in women, older people, and people with diabetes or renal failure.[88][89]​​​ Metoclopramide should be discontinued if the patient does not achieve the desired therapeutic response, or if they develop intolerable or serious adverse effects. One meta-analysis suggested that continuous infusion of metoclopramide, as opposed to bolus administration, reduces the risk of development of extrapyramidal side effects.[90] However, the dose for continuous infusion of metoclopramide has not been studied in patients with gastroparesis. 

Domperidone is an alternative to metoclopramide. In the US, it can only be prescribed to patients through an FDA expanded access to investigational new drugs program. Use of domperidone is, therefore, reserved for patients whose symptoms fail to respond to, or who experience adverse effects with, metoclopramide.[1] It does not cross the blood-brain barrier, so does not cause the neurologic adverse effects associated with metoclopramide. However, it has been associated with QT interval (QTc) prolongation, limiting its use to small doses over less than 1 week in Europe. It should be avoided in patients with prolonged QTc (>450 milliseconds in men, >470 milliseconds in women).[87] FDA: how to request domperidone for expanded access use Opens in new window

A number of macrolide antibiotics act as motilin receptor agonists to promote upper gut transit. Intravenous erythromycin is a potent stimulant of gastric emptying through its action on the motilin receptor, and is often used in the acute care setting if the patient is admitted to the hospital. Although erythromycin is often used for this indication, the evidence supporting its use is limited to diabetic gastroparesis.[47]​ Long-term administration is limited by tachyphylaxis due to downregulation of motilin receptors that starts within a few days of initiating treatment; usage is generally limited to 4 weeks and should be restricted to patients who have not tolerated or responded to other prokinetics.[1][60]

Primary options

metoclopramide: 5-10 mg orally/intravenously four times daily

OR

metoclopramide nasal: 15 mg (1 spray) in one nostril four times daily for 2-8 weeks

More

Secondary options

domperidone: 10-30 mg orally four times daily initially

Tertiary options

erythromycin lactobionate: 3 mg/kg intravenously every 8 hours

Consider – antiemetic

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ACUTE
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acute symptoms
Consider – 

antiemetic

Treatment recommended for SOME patients in selected patient group

Antiemetics are used for symptomatic relief in patients with persistent nausea and vomiting despite use of prokinetic agents; however, they do not improve gastric emptying.[1]​ Rescue antiemetics may also be required during drug holidays with metoclopramide. Antiemetics have not been studied in the management of patients with gastroparesis; their use in gastroparesis is based on their efficacy in controlling nonspecific nausea and vomiting and in patients undergoing chemotherapy.

Histamine H1-receptor antagonists (e.g., diphenhydramine): can have a mild inhibitory effect on gastric emptying.[91]

5-HT3 antagonists (e.g., ondansetron): can be used in patients with persistent symptoms. They are effective in the treatment of chemotherapy-induced vomiting, radiation therapy-induced vomiting, and postoperative vomiting, but controlled studies in gastroparesis are lacking.[68]​ They reduce nausea from stomach distension without affecting gastric compliance, volume, or accommodation. Routine use of these drugs is limited due to the risk of QTc prolongation and, rarely, torsades de pointes, a life-threatening arrhythmia. Baseline and regular electrocardiogram monitoring is recommended.[87]

Phenothiazines (e.g., prochlorperazine): reduce nausea and vomiting via inhibition of dopamine receptors in the brain.[2]​ Their use is limited by the risk of central adverse effects (cognitive, psychomotor, and affective disturbances) and QTc prolongation.

Anticholinergics (e.g., scopolamine): used off-label in gastroparesis despite lack of evidence from clinical trials.[2]

Neurokinin (NK-1) receptor antagonists (e.g., aprepitant): block substance P in critical areas involved in nausea and vomiting, including the nucleus tractus solitarius and the area postrema. Results from randomized controlled trials have been mixed, but the American Gastroenterological Society suggests that up to one-third of patients with refractory nausea may benefit from these drugs.[2]

Neuromodulators: have some antiemetic properties and have a role in refractory gastroparesis. Amitriptyline and nortriptyline are the most commonly used drugs in this class, although evidence for their benefit is limited.[92][93]​​​​ In one prospective, open-label study, mirtazapine was shown to improve nausea, vomiting, and appetite after 2 and 4 weeks of treatment in patients with gastroparesis. However, 46.7% of patients experienced adverse events, and adverse effects led to treatment self-cessation in one-fifth of patients.[94]​ These agents may also be used for pain relief (see below).

Primary options

diphenhydramine: 25-50 mg intravenously/intramuscularly/orally every 4-6 hours when required, maximum 400 mg/day (intravenous/intramuscular) or 300 mg/day (oral)

OR

ondansetron: 4-8 mg intravenously/orally every 8-12 hours when required

OR

prochlorperazine maleate: 5-10 mg orally every 6-8 hours when required, maximum 40 mg/day

OR

scopolamine transdermal: 1 mg/72 hour patch transdermally every 3 days when required

OR

aprepitant: 80 mg orally once daily when required

Consider – analgesia

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ACUTE
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acute symptoms
Consider – 

analgesia

Treatment recommended for SOME patients in selected patient group

Pain can be a prominent symptom in some patients with gastroparesis, leading to significant morbidity and utilization of healthcare resources. There is a lack of clinical trials addressing the treatment of pain in gastroparesis, meaning that treatment options are limited.[1]

Neuromodulators, including tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), can reduce perception of pain at different levels of the brain-gut axis via multiple mechanisms.[2]​ The only gastroparesis-focused study, a randomized placebo-controlled trial of 130 patients, found that nortriptyline was no better than placebo in relieving global symptoms of idiopathic gastroparesis, although some improvement in abdominal pain was observed.[93]

Guidelines differ in their recommendations regarding neuromodulators. The American Gastroenterological Association lists TCAs, SNRIs (specifically duloxetine), anticonvulsants (gabapentin and pregabalin), and mirtazapine as treatment options for visceral pain in refractory gastroparesis, but concedes that there is a lack of high-quality evidence for any of these drugs for this indication.[2] The American College of Gastroenterology advises against the routine use of central neuromodulators.[1]

Opioids are associated with increased severity and duration of symptoms of gastroparesis.[95]​ Pain associated with gastroparesis should therefore not be treated with opioids.[1][2]​ This includes tramadol, which slows orocecal transit, and tapentadol, which slows gastric emptying.[1]

Consider – intravenous fluids

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ACUTE
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acute symptoms
Consider – 

intravenous fluids

Treatment recommended for SOME patients in selected patient group

Not all patients with gastroparesis are hospitalized; however, the majority of patients are admitted to the hospital at least once in their lifetime with an acute episode of severe nausea and vomiting. Dehydration and electrolyte abnormalities can be corrected by intravenous administration of fluid and the appropriate electrolyte: for example, potassium.

Consider – glycemic control

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ACUTE
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acute symptoms
Consider – 

glycemic control

Treatment recommended for SOME patients in selected patient group

Acute hyperglycemia delays gastric emptying; correcting hyperglycemia in patients with diabetes is recommended.[1][57]​ Continuous glucose monitoring and/or an insulin pump may help with dosing and timing of insulin administration in patients with type 1 diabetes or insulin-requiring type 2 diabetes.[57]

Consider – acupuncture

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ACUTE
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acute symptoms
Consider – 

acupuncture

Treatment recommended for SOME patients in selected patient group

Very low-quality evidence suggests that acupuncture alone, or in combination with a prokinetic agent, may provide short‐term symptomatic relief from diabetic gastroparesis. Acupuncture cannot be recommended as beneficial for other etiologies of gastroparesis.[1][96]​ Reported benefit may be attributable to poor methodologic quality of the included studies and, potentially, reporting bias. Further trials, with rigorous methodology, are required.

ONGOING

refractory to medical therapy

1st line – continue medical therapy plus dietary advice plus jejunal feeding tube

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ONGOING
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refractory to medical therapy
1st line – 

continue medical therapy plus dietary advice plus jejunal feeding tube

Patients with gastroparesis who do not respond appropriately to dietary and medical management tend to develop dehydration, electrolyte abnormalities, nutritional deficiencies, and malnutrition. Their diet should be evaluated. In patients who cannot maintain their caloric or nutritional needs, a jejunal feeding tube should be placed for this purpose.

Doses of prokinetics and antiemetics can then be optimized and enteral nutrition can be provided. There is rarely a role for parenteral nutrition, as long-term use is usually fraught with complications such as infections.[83]

Therapy should be tried for at least 2-3 months before trying other treatments.

Consider – gastric electrical stimulation

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ONGOING
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refractory to medical therapy
Consider – 

gastric electrical stimulation

Treatment recommended for SOME patients in selected patient group

This is available for clinical use for patients with refractory nausea and vomiting who have failed standard therapy, who are not on opioids, and who do not have pain as a predominant symptom.[2]​ The precise mechanism of action is unknown, but gastric electrical stimulation does not accelerate gastric emptying. It has been postulated that its beneficial effects may occur via modulation of the gastric pacemaker, interstitial cells of Cajal, sensory afferents, other myoneural pathways, or the release of peptides.[2] The gastric electrical stimulator was granted the humanitarian device exemption by the Food and Drug Administration for diabetic and idiopathic gastroparesis.[1]​ It has been shown to improve nutritional status and glycemic control in people with diabetes, while at the same time reducing the need for prokinetic drugs and healthcare costs.[97][98][99]​ Patients who need this device should be referred to centers with expertise in its implantation. The UK National Institute for Health and Care Excellence has made similar recommendations regarding use of gastric electrical stimulation for gastroparesis.[100]

Consider – surgical or endoscopic treatment

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ONGOING
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refractory to medical therapy
Consider – 

surgical or endoscopic treatment

Treatment recommended for SOME patients in selected patient group

Surgical management is indicated for patients who have refractory and disabling symptoms of gastroparesis, despite maximal medical management and a gastric electrical stimulator. Available surgical options are pyloroplasty, pyloromyotomy, and partial or total gastric resection.[101] Partial or total gastrectomy is rarely required, carries a risk of dumping syndrome, and should only be considered after all available therapies have been considered.[2]​ The decision for surgical management should be made after consultation with a gastroenterologist with expertise in management of gastroparesis.

Gastric per oral endoscopic pyloromyotomy (G-POEM) has shown similar symptom control, with fewer postprocedural complications and shorter length of hospital stay, compared with surgical myotomy.[1]​ The American Gastroenterological Association recommends G-POEM in adult patients with refractory gastroparesis who do not have mechanical gastric outlet obstruction, as confirmed by esophagogastroduodenoscopy, who have had a solid-phase gastric emptying scan to confirm delayed gastric emptying (retention of >20% at 4 hours), and who have moderate to severe symptoms (with nausea and vomiting as the dominant symptoms).[102]​ G-POEM is also recommended in patients who have not responded to gastric electrical stimulator therapy, pyloric stenting, and botulinum toxin injection. Nevertheless, failure of these therapies is not a prerequisite to G-POEM.[102]

Endoluminal functional lumen imaging probe (Endo-FLIP) evaluation may have a role in characterizing pyloric function and predicting treatment outcomes after pyloromyotomy, with patients who have low pyloric distensibility more likely to have improvement in their symptoms and increased pyloric distensibility following surgical intervention.[1][103]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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