Management of Hyperemesis
제일병원 산과 전임의 안현숙
• 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 .
• Nausea is not limited to the morning as implied by the outdated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.)
• 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
• 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)
Risk Factors of HG
- Young age
- Less educations
- 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
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)
• 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.
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
Medical history and clinical presentation (II)
Medical history and clinical presentation (III)
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 (III)
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)
• 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)
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
• 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
• 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)
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 :
-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.
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
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
• 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,
• 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.
• 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