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Gastroparesis

Discuss gastroparesis?

Gastroparesis is a chronic disorder of gastric motility that is characterized by delayed emptying of either solids or liquids or both from the stomach in the absence of any mechanical obstruction.

How common is it?
The precise incidence of gastroparesis is not known, but it is estimated to affect about 4% of the population. Majority of the patients are women and the mean age of onset is 34 years
Aetiology
What are the causes of gastroparesis?
Diabetes, postsurgical (vagotomy, gastric resection, gastric bypass, fundoplication etc) and idiopathic causes account for the large majority of cases. Other causes of gastroparesis include neurological conditions like Parkinsonism, collagen vascular diseases, Chagas disease, hypothyroidism, hyperparathyroidism and hypoparathyroidism.
What are the symptoms of gastroparesis?
Nausea is the most consistent symptom found in over 90% of patients. Postprandial fullness/early satiety and bloating are the other commonest manifestations.

Discuss a severity grading of gastroparesis?
Proposed classification of gastroparesis severity (Abel et al)
Grade 1: Mild gastroparesis
Symptoms relatively easily controlled
Able to maintain weight and nutrition on a regular diet or minor dietary modifications

Grade 2: Compensated gastroparesis
Moderate symptoms with partial control with pharmacological agents
Able to maintain nutrition with dietary and lifestyle adjustments. Rare hospital admissions

Grade 3: Gastroparesis with gastric failure
Refractory symptoms despite medical therapy Inability to maintain nutrition via oral route
Frequent emergency room visits or hospitalizations
How do you diagnose gastroparesis?
As the symptoms are nonspecific with a significant degree of overlap with other gastric disorders, the initial work-up includes an upper endoscopy.  This will exclude any mechanical obstruction or peptic ulcer disease.
Gastric scintigraphy: Gastric emptying scintigraphy of a radiolabeled solid meal is the gold standard for the diagnosis of gastroparesis.   Measurement of emptying of solids is more sensitive by scintigraphy. This is due to the fact that liquid emptying may remain normal despite advanced disease. Consensus recommendations for a standardized gastric emptying procedure have recommended a universally acceptable 99-m technetium sulphur-colloid labelled low fat, egg-white meal. Retention of over 10% of the solid meal after 4 h is abnormal. A grading of severity based on 4 h values might be used: grade 1 (mild), 11%-20% retention at 4 h; grade 2 (moderate), 21%-35% retention at 4 h; grade 3 (severe), 36%-50% retention at 4 h.

Discuss the treatment options?
General measures

  • Stop any medications that impairs gastric motility like opiods, Tricyclic antidepressants (also shown to improve symptoms), Calcium channel-blockers, Clonidine, Dopamine agonists, Lithium Nicotine, Progesterone containing medications and Muscarinic cholinergic receptor antagonists
  • Improve glycemic control- Hyperglycemia itself delays gastric emptying even in the absence of neuropathy or myopathy.   Hyperglycemia can also inhibit the accelerating effects of prokinetic agents[
  • Diet- Multiple small low fat meals about 4-5 times a day. Patients are instructed to take fluids throughout the course of the meal and to sit or walk for 1-2 h after meals.
  • Fats and fiber tend to retard emptying, thus their intake should be minimized. This should be stressed as many of these patients who often concomitantly also have constipation have been told to take fiber supplementation for treatment of their constipation. Carbonated liquids should be avoided to limit gastric distention. If the above measures are ineffective, the patient may be advised to consume the bulk of their calories as liquid since liquid emptying is often preserved in patients with gastroparesis.

Pharmacologic measures

Prokinetic Agents- They should be administered 30 min before meals to elicit maximal clinical effects. Bedtime doses are often added to facilitate nocturnal gastric emptying of indigestible solids.

Dopamine Receptor Antagonists-
Metaclopramide (5-20 mg q.i.d) is a 5-HT4 agonist, a dopamine D2 receptor antagonist and a direct stimulant of smooth muscle, all of which contributes to its prokinetic effect
The overall conclusion from multiple studies is that a minority of patients may experience symptom benefit. However, there appears to be poor correlation between the improvement in gastric emptying and reduction of symptoms.

Patients may develop tolerance over time. Further prolonged treatment with metoclopramide can produce extrapyramidal symptoms. These symptoms usually subside within 2-3 months
of discontinuation of the drug. Irreversible tardive dyskinesia is a catastrophic consequence that occurs in 1% to 10% of cases when metoclopramide is taken for more than 3 months. This condition is disabling and can develop without warning, therefore, it should be
discussed in detail with the patients or their families with documentation of the discussion in their medical record.

Therefore, it is not advisable to maintain patients on metaclopramide for a prolonged period.
It should best be used on a prn basis
Domperidone (10-30 mg q.i.d) is a peripheral dopamine D 2 receptor antagonist with prokinetic properties and a potent antiemetic effect. As it does not cross the blood brain barrier, its central nervous system side effects are minimal.
In clinical trials, the efficacy of domperidone matches that of metaclopramide and cisapride. However, its effect on solid-phase gastric emptying is lost by 6 weeks.

Motilin Receptor Agonists
Erythromycin (50-250 mg q.i.d) exerts its prokinetic effect by stimulating the motilin receptors on smooth muscles and neurons in the gastroduodenal area. However, unlike metaclopramide, erythromycin has no independent antiemetic effect.

Tachyphylaxis develops in patients on chronic erythromycin therapy, due to down-regulation of motilin receptors which can develop as early as a few days of initiating therapy. If tachyphylaxis develops, erythromycin can be discontinued for 2 wk and then restarted
again.  A large cohort reported that erythromycin increases the risk of sudden cardiac
arrest by 2 times when compared to control population.

Symptomatic Therapy
Antiemetic drugs- . The most commonly used antiemetic drugs are the phenothiazines (for example prochlorperazine and thiethylperazine) and they can be used in conjunction with prokinetic agents.
Low-dose tricyclic antidepressants may provide relief of symptoms in patients with gastroparesis.
Pain may be a prominent symptom in some patients. Nonsteroidal agents, selective serotonin reuptake inhibitors and opiates have been used with varying degrees of
success.
Endoscopic Treatment

In some patients with gastroparesis, pylorospasm may contribute to a delay in gastric emptying. Endoscopic therapy involves the injection of botulinium toxin (100–200 units in a circumferential pattern; 4 injections around the pylorus) into the pyloric area, which is thought to decrease pylorospasm and accelerate gastric emptying.
Studies have produced conflicting results with some showing good symptomatic response whereas others showing no benefit.  More studies are required before reaching a final verdict on botulinium toxin injection therapy.

Discuss the role of Gastric pacing/ Gastric electrical stimulation (GES)?

It may be considered in patients with refractory symptoms. Electrical stimulation is delivered by two electrodes usually placed laproscopically on to the serosal surface of the stomach overlying the pacemaker area in the body of the stomach. Leads from the electrodes connect to a pulse generator that resembles a cardiac pacemaker that is implanted in a subcutaneous pocket of the anterior abdominal wall.  The pulse generator delivers low-energy, high-frequency stimuli and has a battery life of 6–8 years.

The exact mechanism of action of the GES is unknown. The clinical effect is believed to be mediated by local neurostimulation. The stimulation impulses used are able to excite nerves but are too weak to excite gastric smooth muscles. Furthermore, poor correlation is
observed between patients’ symptoms and gastric emptying rates.

All trials have produced encouraging results with patients experiencing 75–80% reduction in
symptoms. Other studies indicate sustenance of improvement with long-term benefits lasting 3 – 4 years.

About 10% of patients, however, develop complications like infection, which invariably warrants removal of the device. Other adverse events noted include: lead dislodgement,
wire breakage, penetration of the stomach and intestinal obstruction, all of which require surgical intervention.
Paced GES using an implantable stimulator (Enterra therapy, by Medtronic Inc.) has been approved by the FDA through a humanitarian device exemption.

NICE (2004) recommends ‘Current evidence on the safety and efficacy of gastro electrical stimulation for gastroparesis does not appear adequate to support the use of this procedure without special arrangements for consent and for audit or research’.

Gastric electric stimulation is not ready for prime time yet. Available devices need to undergo further refinement and easier electrode implantation techniques that obviate the need for surgery are required.

What is the role of Surgery?
Extreme cases may require surgical intervention, and operations like partial gastrectomy and pyloroplasty have been performed to treat resistant gastroparesis. The results are unproven so far. Rarely, a venting gastrostomy may be placed to release the discomfort from gas and liquids.

Discuss other treatment options?

  • Enteral and Parenteral Nutrition- Some patients with severe refractory gastroparesis may need enteral or parenteral modes of nutritional support.
  • Enteral nutrition is usually indicated in patients with significant malnutrition and in those who require frequent hospitalizations However, nasogastric tubes and gastrostomy tubes are not encouraged due to the possibility of worsening gastroparesis and risk of pulmonary aspiration. Jejunostomy tubes are preferred in order to bypass the gastroparetic stomach except if the patient has small bowel dysmotility. Short-term nasojejunal feeding is often used to help determine if the patient will tolerate chronic small bowel feeding through a permanent enteral access.
  • Psychological Support- Anxiety, depression and somatization are increasingly found in patients with severe gastroparesis and appropriate psychological support is necessary to improve the overall well-being of the patient. Psychotherapeutic measures like relaxation techniques have been useful. Some patients benefit from hypnosis and biofeedback.

Ref

  1. Waseem S et al. Gastroparesis: Current diagnostic challenges and management considerations World J Gastroenterol 2009 January 7; 15(1): 25-37
  2. Gumaste V et al .Treatment of Gastroparesis: An Update. Digestion 2008; 78:173–179

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