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Management of Hyperemesis
Gravidarum
제일병원 산과 전임의 안현숙
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 .
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• Nausea is not limited to the morning as implied by the outdated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.)
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
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)
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
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.
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.
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
Etiology and Pathology of HG (IV)

Verberg MFG, Gillott DJ, AI-Fardan, Grudzinskas JG. Hyperemesis gravidarum, a literature review. 2005
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.
Medical history and clinical presentation (II)
Medical history and clinical presentation (III)
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
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
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
Treatment strategies II
 Initial management
 Non-pharmacological
interventions
 Pharmacologic
Treatment
 Hospitalization
 Psychosomatic
therapeutic options
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
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)
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
 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
 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
 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.
Antiemetic agents and supposed dosage in hyperemesis gravidarum, adapted from references
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
Recommended procedure for substitution of vitamins during total
parenteral nutrition (personal communication Ramsauer and Vetter, Berlin, Germany)
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 ……,
Algorithm for treatment of nausea and vomiting of pregnancy: If no improvement, proceed to next step.
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.
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
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).
 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.
 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.
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
Thank you for your attention

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Hyperemesis

  • 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. 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. 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. 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. 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. 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. 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. 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. Etiology and Pathology of HG (IV) Verberg MFG, Gillott DJ, AI-Fardan, Grudzinskas JG. Hyperemesis gravidarum, a literature review. 2005
  • 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. Medical history and clinical presentation (II)
  • 13. Medical history and clinical presentation (III)
  • 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. 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. 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. Treatment strategies II  Initial management  Non-pharmacological interventions  Pharmacologic Treatment  Hospitalization  Psychosomatic therapeutic options
  • 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. 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. 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.  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.  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.  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. Antiemetic agents and supposed dosage in hyperemesis gravidarum, adapted from references
  • 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. Recommended procedure for substitution of vitamins during total parenteral nutrition (personal communication Ramsauer and Vetter, Berlin, Germany)
  • 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. Algorithm for treatment of nausea and vomiting of pregnancy: If no improvement, proceed to next step.
  • 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. 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. 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.  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.  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. 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. Thank you for your attention