Summary of Evidence
Diabetic (29%), postsurgical (13%), and idiopathic (36 %) etiologies comprise the majority of cases in tertiary referral setting (8
). Diabetes mellitus
is the most commonly recognized systemic disease associated with gastroparesis. In the NIH consortium cohort, delayed gastric emptying was more pronounced in patients with type 1 DG (10
). The 10-year incidence of gastroparesis has been reported to be 5.2 % in type 1 diabetes, 1 % in type 2 diabetes, and 0.2 % in non-diabetic controls in a US community (5
refers to a symptomatic patient from delayed gastric empting with no detectable primary underlying abnormality for the delayed gastric emptying. This may represent the most common form of gastroparesis (10
). Most patients with IG are women; typically young or middle aged. Symptoms of IG overlap with those of functional dyspepsia; it may be difficult to provide a definitive distinction between the two based on symptoms, and many regard IG and functional dyspepsia with delayed gastric emptying as the same condition. Abdominal pain/discomfort typically is the predominant symptom in functional dyspepsia, whereas nausea, vomiting, early satiety, and bloating predominate in IG. Therefore, measurement of gastric emptying is important, as therapies differ if gastric emptying is delayed, normal, or rapid.
A subset of patients with gastroparesis report sudden onset of symptoms after a viral prodrome, suggesting a potential viral etiology for their symptoms, and the diagnosis of postviral gastroparesis (18
). Previously, healthy subjects have developed the sudden onset of nausea, vomiting, diarrhea, fever, and cramps suggestive of a systemic viral infection. However, instead of experiencing resolution of symptoms, these individuals note persistent nausea, vomiting, and early satiety. Over a period of about a year, the gastroparesis often improves. In general, this course is typical of postviral gastroparesis that is not associated with autonomic neuropathy. On the other hand, a minority of patients with infections due to viruses such as cytomegalovirus, Epstein – Barr virus, and varicella zoster may develop a form of autonomic neuropathy (generalized or selective cholinergic dysautonomia) that includes gastroparesis. These patients with autonomic dysfunction may have slower resolution of their symptoms that may take several years and the prognosis is worse than in postviral gastroparesis without autonomic disorders (20
Postsurgical gastroparesis (PSG), often with vagotomy or vagus nerve injury, represents the third most common etiology of gastroparesis. In the past, most cases resulted from vagotomy performed in combination with gastric drainage to correct medically refractory or complicated peptic ulcer disease. Since the advent of laparoscopic techniques for the treatment of GERD, gastroparesis has become a recognized complication of fundoplication (possibly from vagal injury during the surgery) or bariatric surgery that involves gastroplasty or bypass procedures. The combination of vagotomy, distal gastric resection, and Roux-en-Y gastrojejunostomy predisposes to slow emptying from the gastric remnant and delayed transit in the denervated Roux efferent limb. The Roux-en-Y stasis syndrome — characterized by postprandial abdominal pain, bloating, nausea, and vomiting — is particularly difficult to manage, and its severity may be proportional to the length of the Roux limb (generally, 25 cm is ideal to avoid stasis).
The precise role of the antireflux surgery itself is not clearly demonstrated in the published literature. Thus, while symptoms suggesting gastric stasis are extremely common in the first 3 months after fundoplication, they persist in a minority of patients at 1 year post surgery. In a series of 615 patients who underwent laparoscopic Nissen fundoplication, all had symptoms during the first 3 postoperative months (e.g., early satiety in 88 % and bloating/flatulence in 64 %); however, by 1 year these symptoms suggestive of gastroparesis like bloating/flatulence had resolved in > 90 % of patients (22
). Moreover, among 81 patients with antireflux operations followed for > 1 year, the finding of postoperative symptoms suggesting delayed gastric emptying was usually associated with delayed gastric emptying pre-operatively (23
). The precise role of fundoplication is therefore difficult to determine unless the patient undergoes testing for abdominal vagal dysfunction, such as the plasma pancreatic polypeptide response to modified sham feeding; such tests are described elsewhere (24
In patients with refractory symptoms of GERD, investigation for delayed gastric emptying should be considered, since delayed gastric emptying can be associated with GERD and possibly aggravate symptoms of heartburn, regurgitation, and other symptoms associated with GERD.
Known causes of iatrogenic gastroparesis
include surgical vagal disruption, which may be due to vagal nerve injury (e.g., after fundoplication for GERD), or intentional vagotomy as part of peptic ulcer surgery. The second major category of iatrogenic gastroparesis is induced by pharmacological agents as may occur with narcotic opiate analgesics, anticholinergic agents, and some diabetic medications. Administration of µ-opiate receptor agonists results in delayed gastric emptying and also may cause nausea and vomiting. These include agents such as morphine (25
), as well as oxycodone and tapentadol (26
), but less with tramadol (27
). Therefore, patients receiving such agents should first undergo withdrawal of the agent before assuming a diagnosis of gastroparesis. GLP-1 analogs, such as exenatide, used for treatment of type 2 diabetes mellitus (28
) can delay gastric emptying. In contrast to GLP-1 analogs, which substantially increase plasma GLP-1 concentrations, dipeptidyl peptidase IV inhibitors, which increase plasma GLP-1 concentrations by inhibiting metabolism of GLP-1, do not delay gastric emptying (29
). Nausea (43.5 %) was the most commonly reported adverse event with exenatide treatment, and vomiting was also quite commonly encountered (12.8% (30
)). The antirejection drug, cyclosporine, can delay gastric emptying. Thus, in patients with prior pancreatic transplantation treated with antirejection treatment with cyclosporine, there may be delay in gastric emptying (31
). This does not apply to another calcineurin inhibitor, tacrolimus, which is derived from a macrolide molecule and retains prokinetic properties (32
Other rarer causes of gastroparesis include diseases affecting the extrinsic neural control (such as Parkinsonism, amyloidosis, and paraneoplastic disease) or disorders that result in infiltration or degeneration of the muscle layer of the stomach (such as scleroderma). Mesenteric ischemia should also be considered as a rare cause of gastroparesis that is potentially reversible.