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마더리스크라운드 발표자료

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  1. 1. Management of Hyperemesis Gravidarum 제일병원 산과 전임의 안현숙
  2. 2. Introduction(I) • About 70% - 85% of all pregnancies are accompanied by nausea and vomiting. • Fifty percent of pregnant women have both nausea and vomiting, 25% have nausea only, and 25% are unaffected .
  3. 3. Introduction(II) • Nausea is not limited to the morning as implied by the outdated term of morning sickness. Only 2% experienced only nausea in the morning whereas, in 80%, complaints persisted throughout the day. • The condition is usually selflimiting and peaks at around 9 weeks gestation. At 20 weeks symptoms typically cease, but persists throughout all of pregnancy in 20% of women. • This condition is known as nausea and vomiting during pregnancy (NVP) or emesis gravidarum. (Gadsby R, Barnie-Adshead AM, Jagger C: A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract 1993, 43:245-248.)
  4. 4. Introduction(III) • A small percentage of pregnant women experience a severe form of nausea and vomiting that is termed HG (synonym: excessive vomiting during pregnancy). -Incidence : 0.5% - 2% of all live births. • A standard definition of HG : 1) More than three episodes of vomiting per day w/ ketonuria 2) More than 3 kg or 5% weight loss
  5. 5. Introduction(IV) • Backgroud of Bendectin (1958-1983) Doxylamine, pyridoxine, and dicyclomine Voluntary removal from market in 1983 after a large series of lawsuits alleging an excess of birth defects. • Hospitalizations of pregnant women for severe form of NVP, hyperemesis gravidarum : increased two fold. • Diclectin in Canada. (1979)
  6. 6. Introduction(V)  Risk Factors of HG - Young age - Primigravidas - Less educations - Non-smokers - Overweight or obese - History of motion sickness - History of migraines - Female gender of fetus - Disorder of fatty acid oxidation - Psychological disorders : Anorexa nervosa or bulimia - Genetic predisposition : Monozygotic twins : Inherited glycoprotein – hormone receptor defects
  7. 7. Etiology and Pathology of HG (I) • Unknown etiology…….??? Some biological, physiological and psychological as well as sociocultural factors are thought to be contributory factors. According to another theory : might be an evolutionary adaptation that prevents the intake of potentially noxious food.
  8. 8. Etiology and Pathology of HG (II) Human chorionic gonadotrophin (HCG) • The most likely endocrine factor which accounts for the development of HG. • The incidence of hyperemesis is highest at the time when HCG production reaches its peak during pregnancy (around 9 weeks gestation). • But there is no evidence to support this hypothesis.
  9. 9. Etiology and Pathology of HG(III) Hormonal factors • Estrogens : Increased levels of estrogen and estradiol • Progesterone : Lower and elevated progesterone levels • Hyperthyroidism : physiologically altered during pregnancy, including stimulation by HCG >Transient Hypertyroidism of Hyperemesis gravidarum • Adrenocrticotrophic hormone(ACTH) • Cortisol, Growth hormon, Prolactine Helicobacter pylori infection • Chronic infection with Helicobacter pylori may also cause HG. Psychosomatic approach
  10. 10. Etiology and Pathology of HG (IV) Verberg MFG, Gillott DJ, AI-Fardan, Grudzinskas JG. Hyperemesis gravidarum, a literature review. 2005
  11. 11. Medical history and clinical presentation (I)  Usually non-specific clinical symptoms it is important to exclude the more unusual causes of Nausea and vomiting.  Clinical findings: Dehydration, Weight loss, Acidosis and Alkalosis  Two degrees of severity: i) Grade 1: nausea and vomiting without metabolic imbalance ii)Grade 2: pronounced feelings of sickness with metabolic imbalance.
  12. 12. Medical history and clinical presentation (II)
  13. 13. Medical history and clinical presentation (III)
  14. 14. Differential Diagnoses for HG(I)  Gastrointestinal causes  Metabolic causes • • • • • • • • • • • • • • Appendicitis Diaphragmatic hernia Gastroenteritis Hepatic or cholecystic disorders Hepatitis Ileus and subileus Pancreatitis Stomach cancer Stomach ulcer or duodenal ulcer Addison's disease Diabetic ketoacidosis Hyperthyroidism Porphyria Thyrotoxicosis  Neurological causes • • • • Korsakoff’s psychosis Migrane Vestibular disorders Wernickes’s encphalopathy
  15. 15. Differential Diagnoses for HG(II)  Pregnancy associated  Urogenital causes • Acute fatty liver • Emesis gravidarum (<5 ×/day) • Hyperemesis gravidarum (>5 ×/day) • Multiple pregancy • Pre-eclampsia • Premature contractions • • • • Degenerative uterine fibroids Nephrolithiasis Pyelonephritis Uremia  Other causes • Drug poisoning • Food poisoning • Iron medication
  16. 16. Treatment strategies(I) Therapeutic Purpose: • • • • • Minimize the discomfort of feeling and symptoms Prevent and minimize dehydration and electrolyte imbalance Prevent and minimize ketonuria Proper intake of drinks Prevention of unnecessary hospitalizations
  17. 17. Treatment strategies II  Initial management  Non-pharmacological interventions  Pharmacologic Treatment  Hospitalization  Psychosomatic therapeutic options
  18. 18. Treatment strategies (III) Initial management • • • • • Eat small frequent meals and water avoiding both over distention and complete emptying of the stomach. Mild to moderate NVP prefer carbohydrates and low in fat and acids ; light snack, dairy products, beans, dry and salty biscuits, breads, cereals, crackers, pasta, and rice. Protein-predominant meals; meat, chicken, fish, and eggs. Electrolyte-replacement drinks, oral nutritional supplements Emotional support, psychosomatic care
  19. 19. Treatment strategies (IV) Non-pharmacological interventions • Acupressure : P6 point (Neiguan) on the inside of the wrist but, minimal experimental evidence • Ginger : 250mg po q.i.d. (capsule, tablets, tea) Safety data are not available.  No apparent teratogenic potential safely , up to a daily dose of 1 gram (ACOG : Practice bulletin: nausea and vomiting of pregnancy. Obstet Gynecol 2004) (Ozgoli G, Goli M,Simbar M: Effects of ginger capsules on pregnancy,nausea, and vomiting. 2009)
  20. 20. Treatment strategies(V)  Pharmacologic Interventions • First line therapy: Doxylamine + pyridoxine • • • • • Pyridoxine (Vitamin B6) Doxylamine Dopamine antagonists Phenothiazine Metoclopramide Domperidone / Droperidol • Serotonin 5-HT3 Antagonist : Ondansetron • Anticholinergics • Dicyclomine (spatomin) ®and scopolamine (buscopan) • Corticosteroids • Proton pump inhibitors (PPI) : Lansoprazole Omeprazole • Thiamine • H.pylori Tx. : Antibiotic therapy
  21. 21.  Vitamin B6: 10–25 mg, 3 or 4 times /day  Doxylamine: 12.5 mg, 3 or 4 times /day  Promethazine: 12.5–25 mg q 4h, po or rectally  Dimenhydrinate: 50–100 mg q 4–6h, po or rectally (not to exceed 400 mg /day; not to exceed 200 mg /day if patient also is taking doxylamine)  Metoclopramide: 5–10 mg q 8h po or IM  Trimethobenzamide: 200 mg q 6–8h, rectally
  22. 22.  Thiamine: intravenously, 100 mg daily for 2–3 days (followed by IV multivitamins), is recommended for every woman who requires intravenous hydration and has vomited for more than 3 weeks.  Ondansetron: 8 mg, over 15 minutes, every 12 hours, IV After more conventional therapies have failed
  23. 23.  Corticosteroids appear to increase risk for oral clefts in the first 10 weeks of gestation. Safety, particularly in the first trimester of pregnancy, not yet determined …. • Methylprednisolone: 16 mg q 8h, po or IV, for 3 days.  Taper over 2 weeks to lowest effective dose.  If beneficial, limit total duration of use to 6 weeks.
  24. 24. Antiemetic agents and supposed dosage in hyperemesis gravidarum, adapted from references
  25. 25. Treatment strategies(VI)  Hospitalization • More severe dehydration or ketonuria -Maintaining hydration : most important intervention -Volume and electrolyte replacement : at least 3 L/day -Correction of potential electrolyte imbalance -Administration of vitamins -Parenteral administration of carbohydrate and amino acid solutions : about 8400 to 10,500 kJ/d
  26. 26. Recommended procedure for substitution of vitamins during total parenteral nutrition (personal communication Ramsauer and Vetter, Berlin, Germany)
  27. 27. Treatment strategies(VII)  Psychosomatic therapeutic options • Dialogues between the physician and the pregnant woman : -To evaluate the psychosocial situation in her marital relationship -Activate individual resources -Provide support regarding acceptance of the pregnancy • Other proper therapeutic options such as : -Hypnotherapy -Psychotherapy -Behavioural therapy ……,
  28. 28. Algorithm for treatment of nausea and vomiting of pregnancy: If no improvement, proceed to next step.
  29. 29. Pregnancy outcome and prognosis(I)  In most cases, NVP is self limiting and is usually resolved by around 20 weeks gestation.  NVP and HG may cause considerable direct (for example, medication) and indirect (for example, loss of productivity) costs, which can amount to hundreds of dollars.  Severe NVP is the third leading cause for hospitalization during pregnancy($17,000 per woman).  8.5 million lost working days per year due to NVP.  About 10 % of hyperemesis cases ended in the death of the mother.
  30. 30. Pregnancy outcome and prognosis(II)  More serious medical complications : - Mallory-Weiss syndrome - Esophageal rupture - Pneumothorax - Peripheral neuropathy - Coagulopathy - Wernicke's encephalopathy - Pre-eclampsia - Fetal growth retardation
  31. 31. Summary of recommendations (ACOG Practice Bulletin No. 52 Nausea and Vomiting of Pregnancy, 2004)  The following recommendations are based on good and consistent scientific evidence (Level A): • Taking a multivitamin at the time of conception may decrease the severity of nausea and vomiting of pregnancy. • Treatment of nausea and vomiting of pregnancy with vitamin B6 or vitamin B6 plus doxylamine is safe and effective and should be considered first-line pharmacotherapy. • In patients with hyperemesis gravidarum who also have suppressed thyroid-stimulating hormone levels, treatment of hyperthyroidism should not be undertaken without evidence of intrinsic thyroid disease (including goiter and/or thyroid autoantibodies).
  32. 32.  The following recommendations are based on limited or inconsistent scientific evidence (Level B): • Treatment of nausea and vomiting of pregnancy with ginger has shown beneficial effects and can be considered as a nonpharmacologic option. • In refractory cases of nausea and vomiting of pregnancy, the following medications have been shown to be safe and efficacious in pregnancy: antihistamine H1 receptor blockers, phenothiazines, and benzamides. • Early treatment of nausea and vomiting of pregnancy is recommended to prevent progression to hyperemesis gravidarum. • Treatment of severe nausea and vomiting of pregnancy or hyperemesis gravidarum with methylprednisolone may be efficacious in refractory cases; however, the risk profile of methylprednisolone suggests it should be a treatment of last resort.
  33. 33.  The following recommendations are based primarily on consensus and expert opinion (Level C): • Intravenous hydration should be used for the patient who cannot tolerate oral liquids for a prolonged period or if clinical signs of dehydration are present. • Correction of ketosis and vitamin deficiency should be strongly considered. Dextrose and vitamins, especially thiamine, should be included in the therapy when prolonged vomiting is present. • Enteral or parenteral nutrition should be initiated for any patient who cannot maintain her weight because of vomiting.
  34. 34. Conclusions • HG is a complex and multifactorial condition with significant adverse effects on quality of life. • As soon as possible, accurate diagnosis and management for hyperemesis gravidarum • Proper treatment of individualization
  35. 35. Thank you for your attention