Treatment and Prognosis in Obstetrics & Gynecology Manju Gita Mishra, Hemali Heidi Sinha 
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OBSTETRICS
1
  • Section 1: Problems in Early Pregnancy
  • Section 2: Medical Problems During Pregnancy
  • Section 3: Infections in Pregnancy
  • Section 4: Renal Diseases in Pregnancy
  • Section 5: Antenatal Complications
  • Section 6: Problems During Labor
  • Section 7: Management of Third Stage Complications2
  • Section 1: Problems in Early Pregnancy

Hyperemesis GravidarumChapter 1

Hemali Heidi Sinha
 
INTRODUCTION
Nausea and vomiting are very common symptoms in pregnancy, affecting about 70–85% pregnant women. The usual onset is around the 4th to 7th week of pregnancy, with a peak between 8th and 12th week. Most cases resolve by 20th week of gestation, persistence beyond which may point toward a medical condition.
Hyperemesis gravidarum is a severe form of nausea and vomiting which affects between 0.3 and 2.0% of all pregnancies. Pernicious vomiting may affect homeostasis, electrolyte imbalance, and kidney function and may have adverse fetal consequences.
Uncontrolled vomiting requiring hospitalization, severe dehydration, associated with ketonuria and weight loss of more than 5% body weight is a common clinical feature. Most of these patients also suffer from hyponatremia and hypokalemia. Ptyalism is also a typical symptom.
 
PATHOGENESIS
The exact pathogenesis of hyperemesis gravidarum remains unknown, though a number of hypotheses have been postulated. Many studies have suggested hormonal changes in pregnancy as a cause. Molar pregnancy and trisomy gestation are associated with elevated human chorionic gonadotrophin (hCG) levels. However, hCG levels do not correlate well with the severity of hyperemesis. hCG has thyrotropic action and hyperemesis gravidarum is more common in pregnancies with high hCG levels exhibiting transient self-limiting hyperthyroidism. Antithyroid drugs are not required.
Chronic Helicobacter pylori infection may play a role in hyperemesis. However, seropositivity does not correlate with gastrointestinal symptoms. H. pylori infection has been found in cases of persistent vomiting. Some researchers also postulate that psychological factors might be responsible. Olfactory sensitivity may play a role in the pathogenesis of hyperemesis. Women with vomiting in pregnancy also commonly have a positive family history of hyperemesis.4
 
COMPLICATIONS
 
Maternal Complications
Persistent severe vomiting can lead to dehydration, electrolyte imbalance and ketosis. More serious conditions include esophageal tear or rupture, pneumothorax and peripheral neuropathy due to vitamin B6 and B12 deficiency. Wernicke's encephalopathy has been associated with treatment of hyperemesis gravidarum with intravenous dextrose replacement without thiamine supplement. Central pontine myelinolysis associated with Wernicke's encephalopathy has been reported.
 
Fetal Complications
Uncontrolled hyperemesis gravidarum is associated with fetal growth retardation and fetal death. Infants maybe born prematurely or be small for gestational age. Hyperemesis has a detrimental effect on the weight of newborns. In a study by Veenendaal et al, it was found that women with hyperemesis gaining less than 7 kg weight during pregnancy when compared with women who gained 7 kg or more, the risk of small gestational age infants increased odd ratio (OR) I.5; 95% confidence interval (CI) 1.0–2.2.
Also, babies of women with less than 7 kg weight gain had an increased risk of having babies with a 5 minute APGAR score of less than 7 (OR 5.0, 95% CI 2.6–9.6) compared with babies from a control group.
Hyperemesis by itself is not a risk factor for adverse outcome, but these outcomes are the consequences of low weight gain associated with hyperemesis. With minimal weight gain, adverse outcomes for the newborn are invariably noted. If a mother does have significant weight loss during pregnancy, it creates further complications. In retrospective analysis, patients who had more than 5% weight loss and were malnourished, experienced adverse pregnancy outcomes. These were low birth weight, antepartum hemorrhage, preterm delivery and an association with fetal anomalies. Congenital malformations associated include undescended testicles, hip dysplasia and Down's syndrome. Vomiting is not teratogenic, but untreated electrolyte disturbances, malnutrition and maternal weight loss maybe harmful. There is restriction of activities, and decreased quality of life.
 
CLINICAL EVALUATION
 
History
Hyperemesis occurs commonly in primigravida. When this condition is seen in multipara, it may have occurred in previous pregnancies. There is no associated fever, chills, rigor, headache and visual disturbance in hyperemesis gravidarum.
In the presence of these symptoms, other acute medical or surgical conditions should be excluded.5
 
Physical Examination
A thorough general examination including hydration status, pulse and blood pressure should be performed. A patient with dry lips and tongue, decreased skin turgor and reduced urine output, suggesting dehydration should be admitted for resuscitation and observation. The thyroid should be examined to look for goiter and to elicit signs of thyrotoxicosis. The abdomen should be palpated for uterine size. If the uterus is larger than the period of gestation, and fetal parts are not palpable, molar pregnancy should be ruled out. The pregnancy is best confirmed by ultrasonography. Other conditions that require exclusion are acute pyelonephritis, and acute surgical conditions like renal colic and acute appendicitis.
 
Investigations
The most important immediate investigation is serum electrolyte estimation, because hypokalemia and hyponatremia are common complications in severe hyperemesis gravidarum. These may lead to metabolic alkalosis. Blood should also be tested for urea levels. Urine should be tested for specific gravity and ketone bodies on a daily basis, till specific gravity returns to normal and ketone bodies are negative for at least two days. Daily weight measurement and intake—output records should be maintained.
Other routine investigations for pregnancy if not done earlier should be completed. These include hemoglobin level estimation, ABO grouping and Rh typing, venereal disease research laboratory (VDRL) testing, HIV serology, Hepatitis B and Hepatitis C serology testing.
When the diagnosis is unclear and symptoms persist for more than three days despite treatment, other investigations are required. These are thyroid function tests, complete liver function tests, serum amylase level estimation, and complete renal function test.
 
TREATMENT
 
Nonpharmacologic Management
The management of hyperemesis gravidarum depends on the severity of the patient and should be individualized according to the patient. These range from explanation, emotional support, dietary modification, and antiemetics to more aggressive treatment including hospitalization to correct fluid and electrolyte imbalances. Though there is a range of options from routine changes to medications, alterations in maternal diet and lifestyle can have dramatic effect.
Family members need to be informed that the pregnant mother suffers from hyperemesis gravidarum, and may need to alter her meal times and may require dietary modification, besides tender, love, care and emotional support.6
A large number of patients recover with temporary change in environment, and hospitalization for a short period is beneficial. Patients must be encouraged to rest when symptomatic. These mothers should receive appropriate support from family members.
 
Diet
Modification of the amount and size of meals consumed, may help relieve symptoms. Lesser amounts of food and fluid help to prevent mild cases from getting worse. Meals should contain more carbohydrates than fat. Protein rich diet also relieves symptoms. Drinks should be rich in electrolytes. Citrus drinks are better tolerated than plain water and may be used for rinsing the mouth.
 
Lifestyle
Stress should be avoided and periods of rest increased. Supportive counseling and crisis intervention may be necessary.
 
Acupressure
Some studies have shown that acupressure causes significant reduction in nausea and vomiting. Pressure is applied on a point situated three fingerbreadths above the wrist on the volar surface.
 
Ginger
Root of ginger—Zingiber officinale—has been used for treatment of nausea and vomiting and is considered as an effective antiemetic. In one study, ginger powder in the dose of 1 g per day was more effective than a placebo in reducing nausea and vomiting. Effectiveness is dependent on its aroma, carminative and absorbent characteristics. It acts on the gastrointestinal tract, increasing motility.
Its absorbent property decreases stimuli to the chemoreceptor zone in the medulla inhibiting stimuli to the emetic center of the brain stem. Ginger also blocks the gastrointestinal responses and consequently the nausea feedback.
Despite earlier misgivings on its effect on sex steroid differentiation in the fetus, no teratogenic effects have been found.
 
Pharmacotherapy
In the initial period of severe vomiting, parenteral antiemetics should be administered along with intravenous fluids. The gut requires to be kept empty for the first 24 hours in hyperemesis gravidarum. When vomiting stops and the patient is able to tolerate orally, antiemetics can be prescribed orally.
 
Intravenous Fluid Therapy
Persistent vomiting with ketonuria and dehydration requires admission to hospital and intravenous fluid therapy to replenish the lost intravenous volume.7
Rehydration along with replacement of electrolytes is important in treatment.
Normal saline or Ringer's lactate are the mainstay of fluid therapy. If dextrose solution is used, prior administration of thiamine is necessary to prevent Wernicke's encephalopathy. While replacing electrolytes, care must be taken to consider the risks of rapid infusion to prevent central pontine myelinolysis.
 
Thiamine
The dose for routine supplementation in patients with protracted vomiting is 1.5mg/day. If oral dose is not tolerated, 100 mg of thiamine is diluted in 100 mL normal saline and infused over 30 minutes to one hour weekly.
 
Antiemetics
Commonly used drugs are not advisable prior to 12–14 weeks to prevent detrimental effect to the fetus.
In the 2004 guidelines on vomiting in pregnancy, the American Congress of Obstetrics and Gynecology, recommended that the first line antiemetic medication be intravenous metoclopramide or promethazine. In a double blind study in 2010, it was found that though the therapeutic effects of both drugs were similar, less drowziness was seen with metoclopramide. The dose of metoclopramide is 10 mg and 25 mg of promethazine every 8 hours for 24 hours.
Combination treatment of droperidol and diphenhydramine significantly shortens hospital stay, as well as fewer readmissions compared to those not receiving droperidol or diphenhydramine as primary therapy. The dose of droperidol is 1.0–2.5 mg depending on the severity of symptoms. This dose is administered over 15 minutes. Continuous infusion is started at 1.0 mg/hour and if symptoms persist, the rate is increased to 1.25 mg/hour. The doses are increased by 0.25 mg every 4 hours. No abnormal fetal or neonatal outcomes are noted; neither is any maternal adverse effect including hypotension seen.
Ondansetron is a selective 5-hydroxytryptamine (5HT3) receptor antagonist and acts on central and peripheral nervous system. It delays gastric emptying and decreases vomiting after the first dose, with subsequent decrease in nausea. Patients are able to tolerate a light diet after two days of therapy.
 
Steroids
They act by direct effect on the vomiting center of the brain. It has been found that vomiting ceases within three hours of administration of the first dose of IV hydrocortisone. Maintenance doses range from 15–45 mg/day.
Steroids are used only after all other causes of vomiting have been excluded, or vomiting continues for more than four weeks. Steroids are more effective than promethazine. The dose of methylprednisolone is 16 mg thrice a day.8
 
MANAGEMENT DURING SPECIAL CIRCUMSTANCES
 
Nasogastric Enteral Feeding
With nasogastric enteral feeding, symptoms improve within 24 hours. This treatment has potential complications like pneumothorax, aspiration, infection, and venous thrombosis. It is cheaper than total parenteral nutrition (TPN) and is useful in patients whose nausea and vomiting is associated with consumption of food.
 
Total Parenteral Nutrition
In severe hyperemesis, there is lack of adequate nutrients. TPN provides utilizable nitrogen, electrolytes, trace elements, water and fat-soluble vitamins. It is a non-protein calorie source, generally glucose or lipid emulsion. This source of calories prevent ketosis, which develops from metabolism of fatty acids and may have adverse effect on the fetus.
Complications of the TPN catheter include pneumothorax, puncture of adjacent blood vessel or air embolism. Use of large amounts of glucose may lead to hyperglycemia, leading to fetal anomalies and the risk of macrosomia.
TPN is discontinued when enteral feeding is tolerated.
 
CONCLUSION
Hyperemesis gravidarum is a multifactorial neurohormonal disorder of early pregnancy. It can lead to maternal and fetal complications if not treated early and aggressively. Acute medical and surgical conditions presenting with vomiting should be excluded. A complete history, physical examination and investigations help to establish the diagnosis. Pharmacotherapy along with non-pharmacological treatment successfully controls the symptoms.
SUGGESTED READING
  1. Loh KY, Sivalingam N. Understanding Hyperemesis Gravidarum. Med J Malaysia. 2005;60(3):394–9.
  1. Wegrzynick LJ, Repke JT, Ural SH. Treatment of Hyperemesis Gravidarum. Rev Obstet Gynecol. 2012;5(2):78–84.