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Hyperemesis Gravidarum: Current Concepts and Management N K Kus¸Cu, F Koyuncu

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Hyperemesis Gravidarum: Current Concepts and Management N K Kus¸Cu, F Koyuncu 76 Postgrad Med J: first published as 10.1136/pmj.78.916.76 on 1 February 2002. Downloaded from REVIEW Hyperemesis gravidarum: current concepts and management N K Kus¸cu, F Koyuncu ............................................................................................................................. Postgrad Med J 2002;78:76–79 Hyperemesis gravidarum is a common problem for an The role of serotonin (5-hydoxytryptamine) obstetrician. Though nausea and vomiting are quite was investigated, but no association between increased serotonin secretion and hyperemesis common in pregnancy, hyperemesis is found in only gravidarum was found.11 However, several serot- 1–20 patients per 1000. In this practical review, a onin receptor subtypes have been shown to be general outline of the syndrome, its relation to the related to emesis.12 Helicobacter pylori infection is reported to be gastrointestinal system and thyroid, mild and rare severe associated with hyperemesis gravidarum.13 14 complications, and conventional treatment versus newer Serum IgG concentrations raised against H pylori options are discussed. are higher in patients with hyperemesis gravi- darum when compared with asymptomatic preg- .......................................................................... nant women. Two patients with severe hyperem- esis gravidarum responded dramatically to oral yperemesis gravidarum is defined as vomit- erythromycin therapy, which they were taking for ing in pregnancy that is sufficiently perni- other non-related conditions, and who were later Hcious to produce weight loss, dehydration, found to be seropositive for H pylori.15 Three other acidosis from starvation, alkalosis from loss of patients refractory to standard medical therapy hydrochloric acid in vomitus, and hypokalaemia.1 were given antibiotics and a proton pump inhibi- All these symptoms are not absolutely necessary tor or H2 receptor antagonist and hyperemesis for the diagnosis. Mild to moderate ketonuria resolved.16 Persistent nausea and vomiting beyond may be seen in urinary analysis. High or rapidly the second trimester should raise suspicions of an rising steroids seem to play a part in aetiology, active peptic ulcer caused by H pylori. and raised liver enzymes are seen in 15%–25% of women who are hospitalised.2 Enzyme levels are HYPEREMESIS GRAVIDARUM AND THE not usually increased more than four times the THYROID upper normal limit. Risk factors vary among dif- Thyroid function changes with the onset of preg- ferent populations and female sex of the off- nancy: thyroxine binding globulin, total trii- http://pmj.bmj.com/ spring, several previous pregnancies, and a high odothyronine and thyroxine concentrations, thy- daily intake of primarily saturated fat before roglobulin, and renal iodide clearance all increase. pregnancy are reported to cause a higher risk.3–5 Also hCG has mild thyroid stimulating activity.17 Besides these factors, gestational trophoblastic Transient hyperthyroidism is seen in about 60% of disease, multiple pregnancy, and psychology of patients with hyperemesis gravidarum.18 19 The the patient are other major concerns. Serum increase in thyroid hormones is attributable to amylase levels have been reported to rise in some either higher hCG concentrations, or hCG hyper- on September 24, 2021 by guest. Protected copyright. of the patients with hyperemesis gravidarum, and sensitive thyrotrophin receptors in an overactive this amylase comes from the salivary gland not thyroid,20 or probable secretion of a variant of hCG from the pancreas.6 Immunological factors such with increased thyroid stimulating activity.21 as immune globulins, C3, C4, and lymphocyte Patients with transient hyperthyroidism have no counts were found to be significantly higher in previous thyroid illness, goitre is usually absent, hyperemesis gravidarum, which may suggest a and thyroid antibodies are negative. These pa- role for immunological activity in pregnancy.7 If tients are more likely to have abnormal liver thyrotoxicosis accompanies hyperemesis, mean function tests and electrolytes. The more severe serum β-human chorionic gonadotrophin (hCG), the vomiting the greater degree of thyroid stimu- lation and the higher the concentration of hCG.22 See end of article for IgG, and IgM concentrations rise to a higher authors’ affiliations extent. These factors may exaggerate the stimula- Transient hyperthyroidism may be responsible for ....................... tory effect of β-hCG. In addition, a positive 40%–70% of thyroid function abnormalities in relationship between hyperemesis and maternal pregnancy and usually resolves by 18 weeks Correspondence to: 23 Dr Naci Kemal Kus¸cu, serum prostaglandin E2 concentrations was without treatment and sequelae. Only a small Celal Bayar University, detected.8 proportion of these patients have clinical thyro- School of Medicine, Gastric emptying and intestinal transit times toxicosis and maybe these are the patients who Department of Obstetrics may be delayed in pregnancy because of hormo- secrete a more potent molecular variant of hCG.21 and Gynaecology, Manisa, Turkey 45020; nal or mechanical factors. But, on the contrary, Besides hyperemesis gravidarum occurring dur- [email protected] gastric emptying of solids was reported not to ing the first pregnancy, recurrence in two change during pregnancy9; however, in patients Submitted 13 June 2001 recovering from hyperemesis gravidarum, solid Accepted ................................................. 19 October 2001 emptying time was found to increase, correlating ....................... with abnormal thyroid hormones.10 Abbreviations: hCG, human chorionic gonadotrophin www.postgradmedj.com Hyperemesis gravidarum 77 Postgrad Med J: first published as 10.1136/pmj.78.916.76 on 1 February 2002. Downloaded from consecutive pregnancies has been reported.24 Hyperemesis Newer drugs gravidarum was seen in three consecutive pregnancies and Continuous droperidol infusion and bolus intravenous transient hyperthyroidism was diagnosed in two of them. A diphenhydramine were studied in hyperemesis gravidarum modified variant of hCG was considered to play a part in this and compared with other patients who did not receive any of recurrence. the drugs.42 The study group had a shorter stay in hospital with fewer readmissions. Droperidol-diphenhydramine treat- ment was reported to be both beneficial and cost effective. COMPLICATIONS OF HYPEREMESIS GRAVIDARUM Ondansetron is a 5-hydroxytryptamine receptor antagonist Both relatively benign and pernicious complications may be which is used to prevent severe nausea and vomiting during caused by hyperemesis gravidarum. Weight loss, dehydration, chemotherapy and in the postoperative period. It is listed as a acidosis from malnutrition, alkalosis from vomiting, hypoka- category B drug but is usually avoided during the first trimes- laemia, muscle weakness, electrocardiographic abnormalities, ter. Though serotonin is not implicated in the pathogenesis of tetany, and psychological disturbances may be included in the hyperemesis gravidarum,11 ondansetron may be reserved for “benign” group. Life threatening complications include refractory cases. No adverse effect for either the mother or the oesophageal rupture due to severe vomiting, Wernicke’s fetus was seen in one patient who was treated with the drug encephalopathy, central pontine myelinolysis, retinal haemor- intermittently in every trimester.43 On the contrary, no benefit rhage, renal damage, spontaneous pneumomediastinum, over promethazine has been reported when the two drugs intrauterine growth retardation, and fetal death.25–33 A patient were compared in a double blinded fashion including 15 with hyperemesis gravidarum has been reported to have had patients in each group.44 No difference in the relief of nausea, epistaxis at the 15th week of gestation because of an weight gain, and days of hospitalisation was seen. inadequate intake of vitamin K caused by severe emesis and Steroids may be used as an alternative regimen in patients her inability to tolerate solids and fluids.34 With replacement of refractory to standard therapy. It was first reported in 1953 vitamin K, coagulation parameters returned to normal and the that cortisone treatment led to complete cessation of disorder resolved. Vasospasm of cerebral arteries associated hyperemesis.45 Since then, various forms of therapy have been with hyperemesis gravidarum was reported in two patients.35 used. A short course of methylprednisolone, 16 mg three times The vasospasm was diagnosed by magnetic resonance daily, tapering the dose during the course of two weeks was imaging angiography and the patients responded to fluid and found to be more effective when compared with electrolyte replacement. promethazine.46 There was a significant difference rate in readmission of patients. Birth weight and Apgar scores did not MANAGEMENT OF HYPEREMESIS GRAVIDARUM differ. The drug is thought to exert its effect through the Appropriate parenteral fluid and electrolyte replacement is the chemoreceptor trigger zone located in the brain stem. This initial treatment regimen for hyperemesis gravidarum. Vari- mode of therapy could be begun in the hospital and continued ous antiemetics may be given with vitamin supplementation. in an outpatient setting and reserved for patients refractory to Promethazine, prochlorperazine, chlorpromazine, meclizine, standard intravenous hydration and antiemetics. In another droperidol-diphenhydramine, and metoclopramide are com- study intravenous hydrocortisone was
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