| Level of evidence | Level of agreement* | Agreement achieved | |
|---|---|---|---|
| Section 1. Secondary chronic nausea and vomiting | |||
| Statement 1. In the evaluation of patients with chronic nausea and vomiting, endocrine and metabolic causes should be excluded. | Low | 94% | Yes |
| Statement 2. Chronic nausea and vomiting may be caused by gastrointestinal mucosal inflammation due to pharmacological toxicity, immune‐mediated disorders, or infectious diseases. | Moderate | 91% | Yes |
| Statement 3. Gastrointestinal obstruction should be excluded in patients with chronic nausea and vomiting. | Low | 85% | Yes |
| Statement 4. In patients with chronic nausea and vomiting, current medications should be reviewed to exclude pharmacological causes. | Moderate | 94% | Yes |
| Statement 5. Injuries to the vagal nerve may cause chronic nausea and vomiting following cardiac, thoracic, or abdominal interventions. | Low | 85% | Yes |
| Statement 6. Autonomic dysfunction should be considered in patients with chronic nausea and vomiting. Other symptoms that may suggest dysautonomia include orthostatic hypotension and sweating abnormalities. | Low | 79% | Yes |
| Statement 7. Vestibular disorders may be a cause of chronic nausea and vomiting. | Low | 94% | Yes |
| Statement 8. Vestibular disorders should be considered if chronic nausea and vomiting are accompanied by dizziness and/or vertigo, headache, hearing loss, tinnitus, impaired vision, focal weakness, and difficulty walking. | Low | 91% | Yes |
| Statement 9. Intracranial hypertension can cause chronic nausea and vomiting. | Low | 91% | Yes |
| Statement 10. Signs and symptoms that suggest intracranial hypertension as the cause of chronic nausea and vomiting are headache, visual disorders, vertigo, tinnitus, stiff neck, and/or focal neurologic deficits. | Low | 94% | Yes |
| Statement 11. Patients with anxiety and depression may manifest nausea and vomiting as somatic symptoms of psychological dysfunction. | Moderate | 85% | Yes |
| Statement 12. Nausea and vomiting are symptoms of eating disorders and may be self‐induced or occur as a manifestation of an associated gastrointestinal functional or motility disorder. | Moderate | 91% | Yes |
| Statement 13. In patients with advanced cancer, chronic nausea and vomiting may be caused by antineoplastic agents and radiation therapy; biochemical abnormalities; impaired gastric emptying; visceral and serosal causes of delayed gastrointestinal transit; cranial, vestibular, and cortical causes. | Very low | 91% | Yes |
| Section 2. Motility disorders | |||
| Statement 14. Chronic nausea and vomiting are not characteristic clinical features of primary oesophageal motility disorders. Regurgitation should be differentiated from vomiting. | Very low | 91% | Yes |
| Statement 15. In patients consulting for chronic nausea and vomiting, testing for oesophageal motility disorders (manometry) is recommended only if oesophageal symptoms (regurgitation, dysphagia) are present and structural disease has been ruled out. | Low | 88% | Yes |
| Statement 16. When an oesophageal motility disorder is suspected in patients with regurgitation, and/or vomiting, high‐resolution manometry should be performed after ruling out mechanical obstruction. Complementary tests, as high‐resolution impedance manometry, barium oesophagogram or endoscopic impedance planimetry FLIP may be useful in complex cases. | High | 94% | Yes |
| Statement 17. Chronic nausea and vomiting are frequent symptoms in patients with gastric motility disorders, but pain, early satiety, postprandial fullness and bloating may dominate the clinical picture in many patients. | Moderate | 85% | Yes |
| Statement 18. In patients with chronic nausea and vomiting, a gastric motility disorder may be suspected, especially when associated with diseases or medications that are associated with abnormal gastric emptying. | Moderate | 76% | Yes |
| Statement 19. A gastric emptying test is necessary to establish a diagnosis of gastroparesis in patients with unexplained chronic nausea and vomiting. | Moderate | 91% | Yes |
| Statement 20. Valid methods to measure solid gastric emptying in patients with unexplained chronic nausea and vomiting are scintigraphy and octanoic acid breath tests. | Moderate | 94% | Yes |
| Statement 21. Chronic nausea and vomiting may be characteristic clinical features of intestinal motility disorders, particularly when in presence of concomitant gastric and/or lower GI tract motility disorders. | Low | 88% | Yes |
| Statement 22. Dilated small bowel loops suggest an intestinal motor disorder in patients with chronic nausea and vomiting. | Low | 85% | Yes |
| Statement 23. Patients with confirmed intestinal motility disorders without bowel dilatation may be characterised by chronic abdominal pain. | Low | 76% | Yes |
| Statement 24. Intestinal motility tests (i.e., scintigraphy, stable isotope breath tests, wireless motility capsule, intestinal manometry, abdominal MRI) may be advised in patients with signs of intestinal dysmotility without obstructive or mucosal disorders. | Very low | 79% | Yes |
| Section 3. Disorders of gut‐brain interaction | |||
| Cyclic vomiting syndrome | |||
| Statement 25. Cyclic vomiting syndrome (CVS) refers to recurrent, regular, and stereotypical episodes of nausea and severe vomiting separated by symptom‐free intervals. CVS can be diagnosed only in the absence of other causes (organic or metabolic) that can explain the symptoms. | Moderate | 88% | Yes |
| Statement 26. CVS (defined according to Rome IV) affects about 0.1%‐2% of the adult population. | Low | 88% | Yes |
| Statement 27. Incidence and prevalence of CVS decrease with age. Accordingly, the prevalence of CVS is higher in children than in adults. Prevalence in children reaches 0.2%‐6.2% (also including studies using Rome III for definition). | Moderate | 79% | Yes |
| Statement 28. Typical characteristics suggesting CVS are the onset of episodes early in the morning, episodes lasting at least 48 h, and occurring two or fewer times per month. | Moderate | 76% | Yes |
| Statement 29. A CVS episode typically has four phases: The prodromal phase, the vomiting phase, the recovery phase, and the inter‐episodic or asymptomatic phase. | Moderate | 91% | Yes |
| Statement 30. During the prodromal phase of a CVS episode, patients often experience nausea, sweating, irritability, abdominal pain, fatigue, temperature changes, or insomnia. | Moderate | 82% | Yes |
| Statement 31. The vomiting phase of a CVS episode is characterized by intense vomiting, often bilious, and accompanied by disabling nausea and retching. Abdominal pain is often present and may be severe. Accompanying symptoms may include pallor, listlessness, anorexia, headache, photophobia, low‐grade fever, or hypothermia. | Moderate | 94% | Yes |
| Statement 32. Symptoms resolve during the recovery phase of a CVS episode. | Moderate | 88% | Yes |
| Statement 33. No vomiting is present during the inter‐episodic phase of a CVS episode, patients may be completely asymptomatic with regard to the GI system or may have milder GI symptoms. | Moderate | 91% | Yes |
| Statement 34. Symptoms can be triggered by psychological and physical stress. | Moderate | 91% | Yes |
| Statement 35. Pathogenesis of CVS is multifactorial. | High | 91% | Yes |
| Statement 36. Psychosocial factors are involved in the pathogenesis of CVS. | High | 88% | Yes |
| Statement 37. Gastric emptying is accelerated in the majority of patients with CVS, most of the other patients have normal gastric emptying. In a minority gastric emptying may be (intermittently) delayed. In these, gastroparesis is an important differential diagnosis. | Moderate | 74% | Yes |
| Statement 38. Genetic factors may be involved in CVS. | Moderate | 74% | Yes |
| Statement 39. Neurohormonal factors are involved in the pathogenesis of CVS. | Moderate | 79% | Yes |
| Statement 40. The prevalence of migraine in paediatric and adult CVS patients ranges from about 40% to 70%. About the same percentage of CVS patients have a family history of migraine. | Moderate‐low | 91% | Yes |
| Statement 41. Both, unique and potentially shared, pathophysiologic mechanisms have been observed for CVS and migraine (e.g., regarding genetic background, brain morphology, and function). Therefore, they are considered associated comorbidities but separate entities. | Moderate‐low | 88% | Yes |
| Statement 42. There is an overlap between CVS, functional dyspepsia, and irritable bowel syndrome. | Moderate‐low | 87% | Yes |
| Statement 43. Very little is known about the specific impact of CVS on adults' and children's psychosocial function. | Low | 75% | Yes |
| Statement 44. We recommend that the diagnosis of CVS is based on clinical presentation and relies on the criteria presented in statements 1 and 4‐9 of the CVS section (in analogy to Rome IV criteria). | High | 70% | Yes |
| Statement 45. We recommend that patients with CVS are treated holistically, taking into account lifestyle changes, psychological support, and avoidance of trigger factors. | Very low | 79% | Yes |
| Statement 46. Pharmacological treatment of CVS can be categorized into three groups: Abortive, supportive, and prophylactic therapy. | Moderate | 82% | Yes |
| Statement 47. We recommend that benzodiazepines and antiemetics, including ondansetron, triptans, and aprepitant are used during the prodromal phase to stop an episode of CVS and prevent vomiting. | Moderate | 91% | Yes |
| Statement 48. We recommend that during the vomiting phase energy, fluid, and electrolyte deficits are substituted intravenously. | Moderate | 82% | Yes |
| Statement 49. We recommend that antiemetics, antianxiety medications, and analgesics should be used as needed during the vomiting phase to ameliorate symptoms. | Moderate | 94% | Yes |
| Statement 50. We suggest that opioids are avoided because they may have a sensitizing effect in migraine analgesia. | Moderate | 94% | Yes |
| Statement 51. We suggest that tricyclic antidepressants are used as first‐line therapy for prophylaxis of CVS episodes. | Moderate | 85% | Yes |
| Statement 52. We suggest that as second‐line therapy for prophylaxis of CVS episodes the following substances are used: zonisamide/levetiracetam, L‐Carnitine, coenzyme Q10 and aprepitant. | Moderate | 76% | Yes |
| Statement 53. We suggest that in patients with slow recovery from CVS attacks with symptoms preventing oral food intake for several days enteral or parenteral nutrition is initiated. | Very low | 79% | Yes |
| Statement 54. Cannabinoid hyperemesis syndrome is a cyclic vomiting syndrome induced by high‐dose, prolonged cannabis use. Cannabinoid hyperemesis syndrome and cyclic vomiting syndrome are two distinct entities. | Low | 88% | Yes |
| Statement 55. We recommend that in all patients with suspected cyclic vomiting syndrome, a complete history of cannabis use is performed. | Low | 94% | Yes |
| Statement 56. Cannabinoid hyperemesis syndrome is typically characterized by severe, cyclic episodes (≥ 3/year) of nausea and vomiting with acute onset, and duration of less than a week, in patients with prolonged regular cannabis use (over 2 years). | Low | 85% | Yes |
| Statement 57. We recommend that patients with cannabinoid hyperemesis syndrome undergo withdrawal of cannabis. This is the most effective treatment. | Low | 94% | Yes |
| Statement 58. We suggest that in acute phases, patients are treated with benzodiazepines, haloperidol, and/or topical administration of capsaicin. | Low | 82% | Yes |
| Rumination syndrome | |||
| Statement 59. Rumination is a voluntary but unconscious process in which patients effortlessly bring up recently ingested food from the stomach into the mouth, where it is often then chewed again and re‐swallowed. | Moderate | 91% | Yes |
| Statement 60. The prevalence of rumination syndrome in the adult general population is likely between 0.5%‐5.8% depending on the study population. It is higher in selected populations such as therapy refractory GERD, children, and adolescents. | Moderate | 91% | Yes |
| Statement 61. Dyspeptic symptoms and minor weight loss are common in patients with rumination syndrome. | Very low | 70% | Yes |
| Statement 62. Enhanced visceral pain perception and poor postprandial accommodation of the stomach have been proposed as the mechanisms for epigastric pain and the feeling of “bloating” in patients with rumination syndrome. | Very low | 70% | Yes |
| Statement 63. The mechanism of rumination syndrome is a voluntary but unconscious process that generates a coordinated abdomino‐thoracic muscle response consisting of increased intrabdominal pressure associated to low LOS and intrathoracic pressures. | Low | 85% | Yes |
| Statement 64. The triggering of rumination events is not completely clear but they may be secondary to dyspeptic symptoms as subject seek relief through regurgitation and/or venting. | Low | 76% | Yes |
| Statement 65. Functional dyspepsia, gastroparesis, cyclic vomiting, and other disorders of gut‐brain interaction can overlap and increase the likelihood of rumination syndrome. | Low | 88% | Yes |
| Statement 66. Gastro‐oesophageal reflux disease and pathological supragastric belching can be mechanisms that provoke and/or aggravate rumination syndrome. In cases of non‐responsive gastroesophageal reflux disease, consideration should be given to rumination syndrome. | Low | 85% | Yes |
| Statement 67. Rumination syndrome is independently associated with depression and anxiety. Patients with rumination syndrome have a lower physical and mental quality of life and increased somatic symptom reporting (somatization). | Moderate | 88% | Yes |
| Statement 68. In patients with rumination syndrome, a current or previous associated eating or psychiatric disorder should be considered. | Low | 88% | Yes |
| Statement 69. Combined clinical and objective assessment using high‐resolution manometry impedance is recommended to confirm the diagnosis of rumination. | Low | 76% | Yes |
| Statement 70. Diaphragmatic breathing with or without biofeedback (visual or verbal feedback on abdominal, intercostal, or diaphragm muscle activity using either electromyography or oesophageal impedance manometry) is the first‐line therapy for rumination syndrome. | Moderate | 85% | Yes |
| Statement 71. In patients with rumination syndrome pharmacological treatment with baclofen or tricyclic antidepressants can be used if diaphragmatic breathing/biofeedback are not available or patient does not respond. | Low | 85% | Yes |
| Statement 72. In patients with secondary rumination syndrome, it is necessary to treat underlying gastroesophageal reflux with PPI. | Low | 82% | Yes |
| Statement 73. Although most patients with rumination syndrome have only modest weight loss, patient‐tailored dietetic assessment for severe cases of rumination is indicated. | Low | 85% | Yes |
| Chronic nausea and vomiting syndrome | |||
| Statement 74. Chronic unexplained nausea is defined by the presence of bothersome nausea, at least twice per week on average, in the absence of abnormalities at upper endoscopy or other disease that explains nausea, with symptoms present the last 3 months and started at least 6 months ago. | High | 88% | Yes |
| Statement 75. Chronic unexplained vomiting is diagnosed in patients who had on average at least one episode of vomiting per week, in the absence of an eating disorder, rumination, or major psychiatric disease, in absence of self‐induced induced vomiting, chronic cannabinoid use, or abnormalities in the central nervous system or metabolic diseases likely to explain the recurrent vomiting, with symptoms present the last 3 months and started at least 6 months ago. | High | 88% | Yes |
| Statement 76. Chronic nausea and vomiting syndrome, as defined according to the Rome IV criteria, has an estimated prevalence of 1%. | Low | 94% | Yes |
| Statement 77. Chronic nausea and vomiting syndrome is characterized by continuous, non‐episodic, symptoms of unexplained nausea and vomiting. | Moderate | 85% | Yes |
| Statement 78. The development and maintenance of chronic nausea and vomiting syndrome is best explained by the biopsychosocial model of disease encompassing biological, psychological, and social aspects. | Moderate | 88% | Yes |
| Statement 79. Independent factors associated with chronic nausea and vomiting syndrome are younger age, presence of IBS, and functional dyspepsia. | Moderate‐low | 91% | Yes |
| Statement 80. Psychological distress with mood disorders, anxiety disorders, somatization disorders, and catastrophizing may be associated with chronic unexplained nausea and vomiting. | Low | 91% | Yes |
| Statement 81. Chronic nausea and vomiting syndrome is diagnosed based on clinical criteria after previous exclusion of systemic, organic, or metabolic diseases by objective testing. | Low | 88% | Yes |
| Statement 82. In refractory cases of chronic nausea and vomiting syndrome, gastric electrical stimulation can be considered. | Moderate | 81% | Yes |
| Statement 83. Histamine H1 antagonists (e.g., meclizine, promethazine) are effective for the treatment of chronic nausea and vomiting. | Low | 58% | No |
| Statement 84. Muscarinic M1 antagonists (e.g., scopolamine) are effective for the treatment of chronic nausea and vomiting. | Low | 42% | No |
| Statement 85. Dopamine‐2 antagonists are effective for the treatment of chronic nausea and vomiting. | Low | 73% | Yes |
| Statement 86. 5‐HT3 antagonists are effective for the treatment of chronic nausea and vomiting. | Low | 70% | Yes |
| Statement 87. Tricyclic antidepressants are effective for the treatment of chronic nausea and vomiting. | Low | 70% | Yes |
| Statement 88. Mirtazapine is effective for the treatment of chronic nausea and vomiting. | Low | 76% | Yes |
| Statement 89. Gabapentin is effective for the treatment of chronic nausea and vomiting. | Low | 35% | No |
| Statement 90. Olanzapine is effective for the treatment of chronic nausea and vomiting. | Low | 61% | No |
| Statement 91. Cannabinoids are effective for the treatment of chronic nausea and vomiting. | Low | 29% | No |
| Statement 92. NK‐1 antagonists are effective for the treatment of chronic nausea and vomiting. | Low | 70% | Yes |
| Statement 93. In patients with chronic nausea and vomiting syndrome, attention must be given to adequate nutrition, including vitamins and minerals. | Very low | 94% | Yes |
| Statement 94. Nutritional deficits shall be corrected by dietary modifications and oral supplementation, if possible. | Very low | 91% | Yes |
*Proportion of panellists with level of agreement of 4 or 5 on the 5‐point Likert scale (1: totally disagree, 2: partially disagree, 3: neither agree nor disagree, 4: partially agree, 5: totally agree).