임신 중 입덧의 관리 , 어떻게 할 것인가 ?

June Seek Choi M.D., PhD., Associate ProfessorThe Korean Motherisk Program,

Division of Maternal-Fetal Medicine, Dept. of OB & GYN.,

Cheil General Hospital & Women's Healthcare Center, College of Medicine, Kwandong University, Seoul, Korea

Contents

• Introduction

• Physiology of NVP (nausea and vomiting of pregnancy)

• Management of Hyperemesis Gravidarum

– Non-pharmacologic Treatment

– Pharmacologic Treatment

– Experience of Cheil General Hospital & Women’s

Healthcare Center (doxylamine+pyridoxine)

Introduction(1)

Psychologic condition manifestingthe rejection of the pregnancy by themother

Normal symptom of pregnancy, a potentially life threatening disease process and a physiologic protective mechanism to optimize pregnancy outcomes.

Introduction(2)

Nausea and vomiting of pregnancy

Hyperemesis Gravidarun: weight loss, usually more than 5% of prepregnancy weight

•Young age•History of motion sickness•History of migraines•Female gender of fetus•Disorder of fatty acid oxidation•Genetic predisposition

Monozygotic twinsInherited glycoprotein -hormone receptor defects

Risk Factors

Introduction(3)

• Nausea is not limited to the morning as implied by the

outdated term of morning sickness, and although typically

presenting between 4 and 14 weeks of pregnancy, persists

throughout all of pregnancy in 20% of women.

• 8.5 million lost working days per year due to NVP.

Introduction(4)

• Severe NVP is the third leading cause for hospitalization

during pregnancy($17,000 per woman).

• Bendectin(doxylamine, pyridoxine, and dicyclomine) until

1982 when it was withdrawn from the market unable to

continue to justify the ongoing costs of litigation

• Hospitalization rates for NVP doubled in both the United

States and Canada,but were subsequently reduced in Canada

with the introduction of Diclectin(doxylamine + pyridoxine).

Introduction(5) Fetal consequences of hyperemesis

HyperemesisHyperemesisMajor congenital Major congenital

anomaliesanomalies

< 7kg weight gain< 7kg weight gain

▪▪ Hip dysplasiaHip dysplasia▪▪ Down syndromeDown syndrome▪▪ Fetal coagulopathy orFetal coagulopathy or ChondrodysplasiaChondrodysplasia

▪▪ Low birth weight (RR 2.8)Low birth weight (RR 2.8)▪▪ Preterm birth (RR 3.0)Preterm birth (RR 3.0)▪▪ Fetal death Fetal death

BailitJL. 2005

KallenB. 1987Brunetti-Pierri N et al. 2007

Differential Diagnoses for NVP

Gastrointestinal disordersPeptic ulcer disease/H. pyloriInflammatory bowel diseasePancreatitis AppendicitisBowel obstruction

Hepatic disordersHepatitis Cholecystitis and cholestasis

CNS disordersVestibular disorders (Meniere’s)CNS lesionsDepression/mood disorders

Genitourinary conditionsPyelonephritisOvarian torsion Pelvic

Thyroid dysfunctionTransient hyperthyroidism: 50-70%

•Nausea beginning after 9 weeks’ gestation•Nausea and vomiting antedating the pregnancy•Abdominal pain•Fever•Headache•Goiter•Abnormal neurologic examination•Elevated white blood cell count, anemia, or thrombocytopenia

Physiology of NVP

VestiVestibular bular

& & CNS CNS nausenause

aa

Visceral Visceral & &

chemorechemoreceptor ceptor trigger trigger zone zone

nauseanausea

NVP Histamine,Acetylcholine

Dopamine, Serotonin

•Genetic predisposition,•GI dysrhythmias,•Olfactory hyperacuity, •General physical & Emotional well-being, •Sleep patterns,•Hormone levels; primarily thyroid, HCG and estrogen,

•Helicobacter pylori

↓Alcohol,Smoking

Prevention and Lifestyle Approaches

• There is no one diet that is considered ideal for all women

with NVP.

• Eat small frequent meals avoiding both over distention and

complete emptying of the stomach.

• Mild to moderate NVP prefer carbohydrates; breads,

cereals, crackers, pasta, and rice.

• Profound NVP prefer proteins; meat, chicken, fish, and eggs.

Nonpharmacologic Treatment

• Ginger: 250mg po q.i.d.

capsule, tablets, tea

safety data are not available.

• Acupressure: acupressure point P6 (Neiguan)

There is no theoretical risk associated

with the use of acupressure.

Pharmacologic Treatment(1)

• First line therapy is a combination doxylamine and

pyridoxine.

• Are the symptoms vestibular in nature and, therefore,

more likely to respond to antihistamines or

anticholinergics or are they visceral and, therefore, more

likely to respond to dopamine or serotonin antagonists?

Pharmacologic Treatment(2) Vitamins and Antihistamines

• Vitamin: Vitamin B6, Vitamin B12

• Antihistamine: H1 receptor antagonist,

H2 receptor antagonist

• Doxylamine/Pyridoxine: 2 tablets at bedtime, 1 in the

morning and 1 in the afternoon

Larger body mass index may need up to 8 tablets/day.

H1-receptor antagonist 1st-generation

2nd-generation

3rd-generation

Diphenhydramine, Carbinoxamine, Doxylamine, Clemastine, Dimenhydrinate, Pheniramine, Chlorphenamine (chlorpheniramine), Dexchlorpheniramine , Brompheniramine , Triprolidine, Dimetindene,Cyclizine, Chlorcyclizine, Hydroxyzine, Meclizine, Promethazine,Alimemazine (trimeprazine), Cyproheptadine, Azatadine,Ketotifen

Acrivastine, Astemizole, Cetirizine, Ebastine, Ketotifen,

Loratadine, Mizolastine, Terfenadine

Levocetirizine, Desloratadine, Fexofenadine

Pharmacologic Treatment(3) Antihistamines(H1-receptor antagonist & H2 receptor antagonist)

Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid, Tazac)

H2 receptor antagonist

Pharmacologic Treatment(4) Dopamine Antagonists

• Phenothiazines :

Chemoreceptor trigger zone in the

brain to reduce the nausea and are

considered a second line drug

• Metoclopramide:

Upper gastrointestinal motility

stimulant and gastric dysrhythmia is

associated with NVP

• Domperidone and Droperidol:

Treatment of severe NVP but have

very limited data available.

Phenothiazines

Chlorpromazine: 10-25mg q4-6h po or IM, 50-100mg q4-6h pr

Perphenazine

Prochlorperazine: 5-10mg q6-8h IM or po

Promethazine: 12.5-25mg q4-6h IM or po

Trifluoperazine

Trimethobenzamide

Domperidone: 10-20mg po q6-8h

Droperidol: 0.5-1.0mg/h IV infusion

Metoclopromide: 5-10mg q6h IV or po

May be sedating or rarely cause extrapyramidal effects

Pharmacologic Treatment(5) Others

Nausea and vomiting of pregnancy:treatment algorithm

Dimenhydrinate, 50 mg IV (in 50 mL saline, over20 minutes), every 4 to 6 hoursorMetoclopramide, 5 to 10 mg IV every 8 hoursorPromethazine, 12.5 to 25 mg IV every 4 hoursorProchlorperazine, 5 to 10 mg IV every 4 hours (maximum dose, 40 mg/d)

For patients not tolerating oral intake

Goodwin, 2008

Ondansetron( 온단트 , 조프란 ), 4 to 8 mg orally or IV every 8 hoursorMethylprednisolone, 16 mg orally or IV every8 hours for 3 days. Taper over 2 weeks to lowest effective dose. If beneficial, limit total duration of use to 6 weeks.

For persistent vomiting substitute

Experience of Cheil General Hospital & Women’s Healthcare Center (doxylamine+pyridoxine) (1)

2006.01-2010.05

Experience of Cheil General Hospital & Women’s Healthcare Center (doxylamine+pyridoxine) (2)

2006.01-2010.05

Experience of Cheil General Hospital & Women’s Healthcare Center (doxylamine+pyridoxine) (3)

2006.01-2010.05

Conclusions

• Accurate diagnosis of nausea and vomiting

• Proper treatment of individualization

(Non-pharmacologic Treatment, Pharmacologic Treatment)

Thank you for your attention