1. By: Dr. Ayman Bukhari

2. DEFINITION : Persistent vomiting accompanied by weight loss exceeding 5 percent of prepregnancy body weight and ketonuria unrelated to other causes Although, there is no clear demarcation between common pregnancy-related "morning sickness" and HG

3. The incidence vary from 0.3 to 2 %. Hyperemesis tends to improve in the last half of pregnancy, but may persist until delivery. If vomiting persists beyond a few days postpartum, other etiologies should be investigated.

4. PATHOGENESIS: Unknown. Psychologic factors — a response to stress. Hormonal changes — Elevated serum concentrations of estrogen and progesterone.progesterone HCG peak during the first trimester, the time when hyperemesis gravidarum is typically seen. The predominant theories:

5. Abnormal gastric motility Other — specific nutrient deficiencies (eg, zinc), alterations in lipid levels, changes in the autonomic nervous system, genetic factors, and infection with Helicobacter pylori

6. RISK FACTORS Non-white motion sickness migraine (supertasters) Psychiatric illness pregestational diabetes GTD Multiple Gestation female fetuses>> 1.5 fold

7. DIAGNOSTIC EVALUATION  Weight  Vitals  serum free T4 concentration, serum electrolytes, and urine ketones.  Ultrasound.. GTD and MG..

8. Laboratory abnormalities Hypokalemia Metabolic alkalosis. Metabolic acidosis. An increase in hematocrit, indicating hemoconcentration (ALT) is typically elevated to a greater degree than aspartate aminotransferase (AST). Values for both are typically only mildly elevated, eg in the low hundreds, and rarely as high as 1000 U/L.

9. Hyperbilirubinemia Serum amylase and lipase may increase as much as five-fold (as opposed to a 5 to 10-fold increase in acute pancreatitis).

10. Mild hyperthyroidism, possibly due to high serum concentrations of HCG which has thyroid-stimulating activity. Hypercalcemia due to hyperparathyroidism. This is uncommon, but should be considered as hypercalcemia may contribute to the vomiting.

11. Differential diagnosis based on its first occurrence in early in pregnancy, with gradual resolution over weeks to months. Diagnosis of exclusion

12. Nausea and vomiting that develop after 10 weeks of gestation are not likely due to hyperemesis gravidarum. The presence of  abdominal pain, fever, headache, goiter, abnormal neurologic findings, diarrhea, constipation, or hypertension, also suggests another diagnosis  Surgical Acute Abdomen,Gastritis, Infection, Thyroid.. Etc.. associated symptoms

13. Preeclampsia, HELLP syndrome and fatty liver of pregnancy are also causes but onset is typically in the latter half of pregnancy.

14. TREATMENT Primarily supportive; symptoms usually resolve by midpregnancy regardless of therapy.

15. Fluids and nutrition : Many patients respond to I.V hydration and a short period of gut rest, followed by reintroduction of oral intake. Relief of symptoms is common within one to two days of rehydration

16. IV hydration often includes supplementation of electrolytes as persistent vomiting frequently leads to a deficiency. electrolytes Likewise supplementation for lost thiamine (Vitamin B1) must be considered to reduce the risk of Wernicke's encephalopathy.A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation.thiamine Wernicke's encephalopathy

17. Additionally, mineral levels should be monitored and supplemented; of particular concern are sodium and potassium.sodium potassium After IV rehydration is completed, patients generally progress to frequent small liquid or bland meals.

18. Hospitalization, as well as replenishment of fluids and electrolytes, may contribute to palliation of symptoms. Thiamine supplementation (100 mg intravenously daily for two or three days) is recommended for women who have vomited for more than three weeks. Thiamine

19. Patients whose symptoms are related to delayed gastric emptying should do better with a diet comprised of liquids and low fat solids.

20. Nutritional status and methods of alimentation (eg, tube feedings, parenteral nutrition) should be assessed in conjunction with a nutritionist or nutrition service.

21. The optimal timing for initiating enteral or parenteral nutrition has not been established The decision is based upon clinical judgement. Enteral nutrition via gastric or duodenal intubation is preferable to the parenteral route and may relieve the nausea and vomiting.

22. Nonpharmacologic interventions Triggers — The cornerstone.. Supplements containing iron should be avoided.

23. Dietary changes — as soon as they feel hungry in order to avoid an empty stomach that may aggravate nausea. frequent high carbohydrate, low fat, small meals. Dietary manipulations, such as eliminating spicy foods. Fluids are better tolerated if cold, clear, and carbonated or sour (eg, ginger ale, lemonade) and if taken in small amounts between mealsginger

24. Psychotherapy can also be a useful adjunctive therapy, particularly if psychological sources of anxiety are identified and can be ameliorated.

25. Pharmacologic treatment A reasonable approach is to begin therapy with agents that appear to be effective and have shown minimal side effects and, if these are ineffective, substitute other drugs in a step-wise progression. Algorythm:

27. no medication is considered completely risk-free for use during pregnancy The standard treatment in most of the world is vitamin B6

28. Pyridoxine and doxylamine succinate — Systematic reviews of randomized and/or controlled studies have shown that pyridoxine (vitamin B6) (10 to 25 mg orally three or four times per day) improves mild to moderate nausea, but does not significantly reduce vomiting.vitamin B6 Thus, it is most useful for women with morning sickness rather than hyperemesis. Doxylamine succinate is an antihistamine that is usually taken with pyridoxine. The combination appears to improve efficacy and was the formulation for Bendectin. Doxylamine

29. Antiemetic drugs, especially ondansetron (Zofran), are effective in many women. The major drawback of ondansetron has been its cost. In severe cases of HG, the Zofran pump may be more effective than tablets. Antiemeticondansetron Metoclopramide is sometimes used in conjunction with antiemetic drugs; however, it has a somewhat higher incidence of side effects. Metoclopramide

30. Other medications less commonly used to treat HG include Marinol, corticosteroids and antihistamines.Marinolcorticosteroidsantihistamines

31. Antihistamines (H1 antagonists) —promethazine (12.5 to 25 mg every four hours orally, I.M, or P.R) for the initial choice of antiemetic in women who do not respond to VitB6promethazine

32. Antacids — Pregnant women often develop gastroesophageal reflux (heartburn), which can worsen nausea and vomiting.

33. Practice in United Kingdom: The first choice drug is promethazine with second choice being either metoclopramide or prochlorperazine; with the administration of thiamine strongly recommended.promethazinemetoclopramide prochlorperazine

34. If all failed !!!

35. Corticosteroids have been used in women with severe and refractory hyperemesis, although the mechanism of action is not well understood Corticosteroids The role of corticosteroids for hyperemesis is unsettled. Most obstetricians avoid chronic administration of corticosteroids in pregnant women, when possible, because prolonged use appears to increase the risk of preterm premature rupture of membranes (PPROM). There may also be a slightly increased risk of oral clefts when the drugs are administered before 10 weeks of gestationcorticosteroids

36. [If administered after 10 weeks (when the palate has formed), the usual dose is methylprednisolone 16 mg orally or intravenously every eight hours for three days. The drug can be :methylprednisolone  stopped abruptly if there is no response,  tapered over two weeks in women who do have relief of symptoms.

37. Secular Trends in the Treatment of Hyperemesis Gravidarum

38. Complications For the pregnant woman Electrolyte imbalance.. If inadequately treated renal failure, central pontine myelinolysis, coagulopathy, Mallory-Weiss syndrome, hypoglycemia, jaundice, malnutrition, Wernicke's encephalopathy, pneumomediastinum, rhabdomyolysis, splenic avulsion and vasospasms of cerebral arteries. Depression is a common secondary complication of HG.renal failurecentral pontine myelinolysiscoagulopathyMallory-Weiss syndrome hypoglycemiajaundicemalnutritionWernicke's encephalopathypneumomediastinum rhabdomyolysisDepression

39. For the fetus Children born to hyperemetic women appear to have no greater risk of complications or birth defects than the general population. However, recent research in fetal programming indicates that prolonged stress, dehydration and malnutrition during pregnancy can put the fetus at risk for chronic disease, such as diabetes or heart disease, later in life, or neurobehaviorial issues from birth.

40. OUTCOME AND PROGNOSIS — the availability of I.V.F and parenteral nutrition has greatly reduced morbidity, and mortality is virtually nonexistent in patients who are treated. If left untreated, micronutrient deficiency, Wernicke encephalopathy (from deficiency of vitamin B1), and sequelae of malnutrition (immunosuppression, poor wound healing) have been reportedvitamin B1 Esophageal tears and rupture are other rare complications.

41. women with severe vomiting who require multiple hospitalizations may not have "catch up" weight gain; an adverse effect on birthweight is more likely in these women.

42. The disease is likely to recur in subsequent pregnancies. The risk of recurrent hyperemesis in next preg. 15-20 %

43. OUTCOME — Most women with pregnancy-related nausea and vomiting recover completely without any complications.

44. In women with severe nausea and vomiting who are hospitalized multiple times and who do not gain weight normally during pregnancy, there is a small risk that the baby will be underweight or small.

45. Thank You