II. Definitions
- Hyperemesis Gravidarum
- Severe, intractable Vomiting in Pregnancy
III. Epidemiology
- Incidence: 1-2 per 200 pregnancies (up to 3% in some series)
IV. Pathophysiology
- See Morning Sickness
V. History: Diagnosis
- Intractable Vomiting with systemic effects
- Ketonuria (Acetonuria)
- Weight loss (typically 5% of pre-pregnant weight)
- Dehydration
- Electrolyte disturbance
- Occurs in first trimester
- Peak Incidence at 10-12 weeks
- Often worse in morning
- Quantify Vomiting
- Establish inability to tolerate oral fluids
- Urinary symptoms
- Decreased Urine Output
- Dysuria
- Flank Pain
VI. Signs
- Weight loss, or no weight gain
- Tachycardia
- Dry mucus membranes
- Poor Skin Turgor
- Fever
- Uterine Size
- External Fetal heart tone monitoring
VII. Precautions
- Hyperemesis before 4 weeks or after 12 weeks gestation may suggest other cause
- Consider differential diagnosis as below
VIII. Differential Diagnosis
- Gastrointestinal causes
- Genitourinary causes
- Endocrine causes
- Neurologic causes
- Miscellaneous conditions
- Pregnancy-Related causes
IX. Labs
- Basic Chemistry Panel (basic metabolic panel)
-
Liver Function Test (or as part of comprehensive metabolic panel)
- Aminotransferases (AST, ALT) may exceed 200 IU/L
- Serum Bilirubin and Alkaline Phosphatase may be increased up to twice normal
- Complete Blood Count
-
Urinalysis
- Evaluate for Urinary Tract Infection
- Ketonuria (or Ketonemia) was previously used as a marker for hyperemesis severity
- Urine Ketones do NOT correlate with hyperemesis severity
- (2014) Am J Obstet Gynecol 211(2): 150 +PMID:24530975 [PubMed]
- Urine Culture
- Quantitative bhCG
-
Thyroid Function Test: Free T4 and Thyroid Stimulating Hormone (TSH)
- Previously recommended routinely
- As of 2015, only recommended for hyperemesis with Hyperthyroidism symptoms, signs
X. Imaging
-
Ultrasound
Pelvis
- Previously used to evaluate for Molar Pregnancy or Multiple Gestation
- However, ACOG does not recommend routine Ultrasound solely for hyperemesis (unless otherwise indicated)
-
Ultrasound Right Upper Quadrant
- Gallbladder and Pancreas
XI. Management: Non-prescription management
- See Morning Sickness for non-pharmacologic measures
- Dietitian Consultation
- See Morning Sickness
- Over the counter agents: Vitamins
- Pyridoxine (Vitamin B6)
- Dose: 25 mg orally every 6-8 hours
- Often used in combination with other agents below (e.g. Doxylamine)
- Pyridoxine (Vitamin B6)
- Over-the-counter agents: Antihistamines
- Diphenhydramine (Benadryl)
- Dose: 25-50 mg IM/IV/PO q4-6 hours
- Maximum: 400 mg in 24 hours
- Meclizine (Antivert)
- Oral: 25-50 mg PO q6 hours
- Consider using concurrently with Phenergan
- Dimenhydrinate (Dramamine)
- Dose: 50-100 mg every 4-6 hours
- Maximum: 300 mg in 24 hours
- Doxylamine (Unisom, Diclectin)
- Dose: 10 mg up to three times daily
- Diphenhydramine (Benadryl)
- Combination
- Doxylamine 10 mg and Pyrodoxine 10 mg (Diclegis, previously Bendectin and Diclectin in Canada)
- Dose: Start with 2 tabs in PM and may advance to 1 in AM, 1 at Noon and 2 in PM
- Originally pulled from market due to safety concerns that were unsubstantiated
- Diclegis is very expensive ($570/month) until generic in 2019
- However, generic Doxylamine and Pyridoxine are inexpensive at $20/month
- Bonjesta (extended release Doxylamine 20 mg and Pyridoxine 20 mg)
- Released in 2018, very expensive and no significant added benefit aside from frequency
- (2013) Presc Lett 20(6): 32-3
- (2018) Presc Lett 25(5): 29
- Doxylamine 10 mg and Pyrodoxine 10 mg (Diclegis, previously Bendectin and Diclectin in Canada)
XII. Management: Prescription Antiemetics (Take 1/2 hour prior to meals)
- See other general management and OTC Medication options above
- First-line agents
- Consider adding Pyridoxine (Vitamin B6) with or without Doxylamine as listed above
- Metoclopramide (Reglan)
- Dose: 10 mg orally four times daily or 1-2 mg IV
- Risk of Dystonic Reaction (as high as 20%) and Tardive Dyskinesia (rare)
- Second-line agents
- Prochlorperazine (Compazine)
- Parenteral and oral: 5-10 mg IM/IV/PO q4-6 hours
- Suppository: 25 mg PR q6-8 hours
- Promethazine (Phenergan)
- Risk of neonatal respiratory depression near term or during labor
- Dose: 12.5-25 mg PO/PR q4-6 hours
- Maximum: 100 mg in 24 hours
- Vistaril
- Dose: 25-50 mg IM/PO q4-6 hours
- Prochlorperazine (Compazine)
- Refractory hyperemesis management
- Ondansetron ODT (Zofran ODT)
- Dose: 4 mg orally up to every 6 hours
- Commonly used in U.S. for hyperemesis
- Although had appeared safe in pregnancy, longterm data were lacking (compared with other agents)
- Ondansetron may be associated with 2 fold risk of Congenital Heart Defects and Cleft Palate
- ACOG recognizes the inconsistent findings and notes low risk to the fetus
- (2014) Presc Lett 21(1): 5
- Koren (2012) Can Fam Physician 58(10):1092-3 [PubMed]
- Corticosteroid regimen
- Methylprednisolone 16 mg PO tid, taper over 2 weeks
- Risk of Cleft Palate with first trimester use
- Ondansetron ODT (Zofran ODT)
XIII. Management: Agents to avoid (mixed or absent safety data)
- Avoid Droperidol
- Avoid Phosphorated Carbohydrates (Emetrol)
- No evidence of benefit and as much Glucose as 2 cans of regular soda
- Avoid Scopolamine in first trimester (risk of limb and trunk abnormalities)
XIV. Management: Emergency Department protocol
- Initial Fluid Replacement
- Approach
- Dextrose containing solutions may be preferred (but conssider Thiamine replacement at the same time)
- First: Isotonic Saline (NS or LR or D5LR) 1-2 liter bolus
- Next: D5LR with 20 KCl at 150 cc/h
- Approach
-
Thiamine indications (prevention of Wernicke Encephalopathy)
- Transitioning to dextrose solutions
- Vomiting >3 weeks or IV fluid >3 days
- Inpatient
- Follow daily weights
- Follow Input and Output
XV. Resources
- Gardner in U.S. Pharmacist
XVI. Complications
- Vomiting-induced GI Trauma (e.g. Mallory Weiss Tear)
- Electrolyte abnormalities (e.g. Hypokalemia, Hyponatremia)
- Thiamine deficiency (Wernicke Encephalopathy)
- Acute Kidney Injury
- Severe weight loss in pregnancy
XVII. References
- Delaney in Herbert (2018) EM:Rap 18(1): 12-4
- Mayo and Welsh (2021) Crit Dec Emerg Med 33(5): 12
- (2015) Obstet Gynecol 126(3): 687-8 +PMID: 26287781 [PubMed]
- Broussard (1998) Gastroenterol Clin North Am 27(1):123 [PubMed]
- Eliakim (2000) Am J Perinatol 17(4):207-18 [PubMed]
- Herrell (2014) Am Fam Physician 89(12): 965-70 [PubMed]
- Kuscu (2002) Postgrad Med 78(916):76-9 [PubMed]
- Quinlan (2003) Am Fam Physician 68(1):121-8 [PubMed]