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Midwifery co-management of hyperemesis gravidarum
MIDWIFERY CO-MANAGEMENT OF HYPEREMESIS GRAVIDARUM Joan Slager,
CNM, MSN
and J. Patrick Lavery,
ABSTRACT Hyperemesis gravidarum is an infrequent, yet significant, maternal complication of pregnancy. Beginning with the frequently experienced nausea and vomiting of pregnancy, symptoms can progress to hyperemesis, a debilitating condition affecting maternal and fetal well-being. A basic understanding of the pathophysiology of the disease process and an awareness of the therapeutic interventions that are available will facilitate midwifery planning for either the collaborative care or the potential referral to medical management, both of which may be required with this clinical entity. The diagnosis and initial management of hyperemesis is within the purview of midwifery care. As certain critical features of duration and severity evolve, medical collaboration and ultimate hospitalization may be required. For those few individuals requiring the most intense level of care, the critical support and encouragement afforded by midwifery participation will contribute to timely resolution of this debilitating condition. This article discusses the continuum from differential diagnosis to ultimate care of the woman who has excessive nausea and vomiting of pregnancy. Collaboration among health care providers will allow all to exercise their respective skills in achieving the optimum in safe therapy and support for their patients. J Midwifery Womens Health 2000;45:457– 64 © 2000 by the American College of Nurse-Midwives. INTRODUCTION
Nausea and vomiting in early pregnancy is common, affecting a significant number of all women during pregnancy. When it reaches the clinical picture of a metabolic disturbance with weight loss, alkalosis, dehydration, hypokalemia, and altered nutritional status, the diagnosis of hyperemesis gravidarum (HG) is made. More than 50,000 pregnant women are hospitalized each year in the United States for HG for an average of 4 days (1). The criteria for the diagnosis have ranged from the arbitrary need for hospitalization to a metabolic disturbance associated with persistent vomiting, large ketonuria, and loss of more than 5% of body weight. Resolution is usually achieved by midpregnancy. However, in the interim, this condition may pose a diagnostic and therapeutic challenge for the care provider and incalculable misery for the afflicted gravida. This article discusses the physiology, differential diagnosis, and therapeutic aspects of HG. The progression from midwifery diagnosis and evaluation to the comple-
Address correspondence to Joan Slager, CNM, MSN, Bronson Medical Office Pavilion, 601 John Street, Suite M-351, Kalamazoo, MI 49007.
MD
ment of medical interventions illustrates the critical roles played by the respective providers to achieve a successful outcome. It challenges certified nurse-midwives (CNMs)* and certified midwives (CMs)* who must frequently evaluate the patient, initiate appropriate diagnostic studies, and facilitate the use of a broad armamentarium of pharmacologic agents and nonpharmacologic interventions for therapy. The use of midwifery* skills in clinical diagnosis and support is essential for the patient so affected. The medical resources that are often implemented will be reviewed in this discussion so as to delineate the parameters for initiating collaborative care or primary medical management. Ongoing midwifery participation in the care of the patient often contributes to a more satisfactory outcome as medical therapy is implemented. The impact of nausea, vomiting, and ultimately, hyperemesis cannot be overstated. In one study, nearly 50% of employed women believed that their work efficiency was affected by pregnancy-related nausea and vomiting and as many as 25% required time off (2). In a similar review, Gadsby et al (3) found that of 206 pregnant women in paid employment, 35% spent an average of 62 hours away from their job. The personal and social impact of this clinical disturbance is clearly quite significant; thus, midwives* should be prompt in the assessment, management, and initiation of therapy for this complex and occasionally progressive malady of gestation. PHYSIOLOGY
Reports indicate that 66 –70% of gravid women have nausea and that 18 – 44% experience significant vomiting in pregnancy (3,4). Nausea and vomiting of pregnancy typically begin at 4 – 6 weeks of gestation, reaching their most severe degree at 8 –12 weeks and abating by 20 weeks. The diagnosis of “hyperemesis” with associated metabolic disturbances occurs in 3.3–10 per 1,000 pregnancies (5). Clinical conditions that show a statistical association with hyperemesis diagnosis include increased body weight, nulliparity, multiple gestation, gestational * CNMs/CMs and midwives as used herein refer to those midwifery practitioners who are certified by the American College of Nurse-Midwives (ACNM) or the ACNM Certification Council, Inc.; midwifery refers to the profession as practiced in accordance with the standards promulgated by the ACNM.
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trophoblastic disease, a history of previous hyperemesis, and a pregestational high-fat diet (72 g/day), particularly in saturated fats (1). Hyperemesis is seen less frequently in smokers and women older than 35 years of age (5,6). Fetal factors associated with hyperemesis include triploidy (partial mole), trisomy 21, and hydrops fetalis (7). The reason for such associations is not clear. Aneuploidy (particularly trisomy 21) has been associated with elevated human chorionic gonadotropin (hCG) levels, (8); however, the association between hyperemesis and rising total hCG levels, once thought significant, has been disputed by Abel and Riely (5). The specific cause of hyperemesis is unknown. However, certain clinical factors have been suggested as contributors to the pathophysiology of hyperemesis; these include increased sensitivity of the chemoreceptor trigger zone (CTZ); disturbances in gastric motility (similar to diabetic gastroparesis) mediated by progesterone; and the influence of pregnancy-related hormonal change, including hCG, thyroxin, and cortisol. Psychological and social factors have been likewise implicated as has a lack of (less than 12 years) formal education (9). Frigo et al (10) have described a strong association with the presence of Helicobacter pylori IgG antibodies (90.5%) in patients with HG as opposed to 46.5% in the control population. In an extensive review of the various causes of hyperemesis, Abell and Riely (5) found no substantial or consistent factor among the multiple proposed causes of this significant clinical problem. Recently, Goodwin et al (11,12) have reported the finding of significantly higher concentrations of total hCG and the free  subunit of hCG in women with true hyperemesis compared with controls. A greater predilection to HG has been seen in Asian populations (13); this has been associated with specific isoforms of hCG and hyperthyroidism, suggesting that genetically determined predilections to HG exist, at least in this studied population. Mori et al (14) have demonstrated the thyroid-stimulating effect of hCG leading to an increase in free thyroxine (T4) and decrease in thyroid-stimulating hormone (TSH). This “biochemical” appearance of hyperthyroidism should not be confused with actual Graves’ disease. Resolution of the biochemical picture will occur,
Joan Slager is director of nurse-midwifery for the Bronson Women’s Service at Bronson Methodist Hospital, Kalamazoo, Michigan. She received her nurse-midwifery certificate from the community-based Nurse-Midwifery Education Program at the Frontier School of Midwifery and Family Nursing in 1991 and her Masters of Science in Nursing from Case Western Reserve University in 1993. J. Patrick Lavery is a perinatologist at Bronson Methodist Hospital, Kalamazoo, Michigan. He also serves as Bronson’s Medical Director of Women’s Reproductive Services. Dr. Lavery is a professor of obstetrics, gynecology, and reproductive medicine at Michigan State University, East Lansing, Michigan.
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and the hCG levels decline as symptoms abate generally after 16 –18 weeks’ gestation. Continued clinical problems and lack of remission of the symptoms may warrant further evaluation. Goodwin and Mestman (12) have shown a significant correlation between the severity of hyperemesis and transient disturbances in thyroid function, as measured by the T4 index and suppressed thyrotropin. Although biochemical levels may measure in the hyperthyroid range, this syndrome generally does not require antithyroid medication and resolves spontaneously with the diminution of symptoms (15). To facilitate differentiation between true thyroid disease and hyperemesis, the finding of a TSH level of 0.1 mU/L (lower than seen with hyperemesis), an elevated FT4 and/or FT3 suggest coexistent hyperthyroidism.
FETAL OUTCOMES
Even with the diagnosis of hyperemesis, the rate of pregnancy loss has been reported lower than expected in the general population (5). Although it would at least suggest that the metabolic disturbances incurred with the process do not have significant adverse fetal effects, Gross et al (16) reviewed pregnancy outcome from a fetal growth perspective and reported that fetal growth retardation was more prevalent (30% v 6%) in the population experiencing more than 5% weight loss when hyperemesis was present in early pregnancy. They suggested that weight loss and metabolic disturbance in early gestation may be a distinct entity placing the fetus at risk for subsequent growth problems. Other studies (17,18) have looked at later pregnancy outcome and have reported more favorable results for the fetus after early pregnancy hyperemesis. Hallak et al (17) reviewed data on 40 patients with mild hyperemesis and 98 with severe hyperemesis. When compared with the 12,335 nonaffected gravidas who served as controls, there was no difference when fetal growth, prematurity rates, incidence of congenital malformations, newborn parameters of Apgar score, and NICU admissions were considered. Tsang et al (18) also reported a similarly favorable outcome in their population of 193 women with HG. These women represented 1.5% of their total population (13,053) in which there were similar outcomes when mean birth weights, incidences of prematurity, Apgar scores, perinatal mortality, and incidences of anomalies were compared. In summary, research related to the long-term consequences of hyperemesis for the fetus has not thus far resolved all of the issues; however, there is good supporting information suggestive of a favorable fetal prognosis despite hyperemesis in early gestation.
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DIFFERENTIAL DIAGNOSIS
When a pregnant woman with hyperemesis initially is seen for midwifery care, it is important to promptly assess the patient’s clinical picture and initiate appropriate diagnostic studies. Underlying diseases should be ruled out. Initiation of conservative pharmacologic therapy, dietary counseling, and psychological support will be effective in most cases. A detailed history should be taken when a woman has nausea and vomiting in pregnancy. A previous pregnancy afflicted by hyperemesis is often a clue to recurrence; however, primary medical and surgical conditions must be considered before such a conclusion can be drawn. Elements of the history should include potential for acute problems such as food poisoning, diet history, the frequency of vomiting episodes, relationship of the vomiting to intake, the nature of the vomitus, and psychological factors precipitating the vomiting, if any exist. Sensitivity to food odors is more characteristic of hyperemesis than other medical causes of significant vomiting, whereas the presence of fever, chills, or localized pain is more suggestive of an inflammatory process. The history of any medical condition warrants further attention. Conditions such as chronic pancreatitis, Crohn’s disease, and other inflammatory bowel disease may be exacerbated in pregnancy. Assessment for weight loss is also an essential part of the diagnostic work-up. The continued evaluation of a patient with HG must take into consideration pregnancy-related conditions and other systemic processes (see Table 1). A prior medical history of gastrointestinal (GI) or renal problems may be significant. Critical diagnoses to eliminate are inflammatory GI disorders (eg, appendicitis, cholecystitis, and pancreatitis), pregnancy-related problems (multiple gestation, trophoblastic disease), and other systemic medical disorders (diabetes, acute renal disease, pyelonephritis, and metabolic disorders such as hyperthyroidism and hyperparathyroidism). Unless a specific diagnosis of hyperthyroidism is made, antithyroid hormonal therapy is not required, because both hyperemesis and chemical hyperthyroidism appear to resolve with the passage of time (5). The physical examination should be complete and comprehensive observing carefully for signs of dehydration. In addition to monitoring the vital signs, assessment should include assessment of the lips and mucous membranes, the turgor of the skin, urinary output, and concentration of the urine. This evaluation will give some indication of the presence and severity of any dehydration and will dictate the degree of intervention that is warranted. Abdominal examination should include assessment of bowel sounds, point tenderness, and organomegaly (19). In the case of hyperemesis, abdominal findings are usually mild and nonspecific. Localizing
TABLE 1
Considerations in the Differential Diagnosis of Hyperemesis Gravidarum Pregnancy-related Multiple gestation Trophoblastic disease Fetal anomalies/aneuploidy (see text) Genitourinary disorders Pylonephritis Uremia Kidney stones Degenerating leiomyomata Gastrointestinal disease Biliary tract (gallbladder) disease Hepatitis Pancreatitis Appendicitis Gastroenteritis Peptic ulcer disease Gastroesophageal reflux disease Intestinal obstruction Metabolic problems Hyperthryoidism (thyrotoxicosis) Hyperparathyroidism Diabetic ketoacidosis Porphyria Addison’s disease Central nervous system disorders Pseudotumor cerebri Brain tumor Neuropsychiatric diagnoses Migraine headache Vestibular nerve stimulation Increased intracranial pressure Meningeal irritation
symptoms are more suggestive of specific disease entities such as appendicitis and pyelonephritis. On physical examination, eliciting point tenderness, rebound pain, and finding ileus with tympanitic percussive findings and hypoactive bowel sounds are more suggestive of an inflammatory disease than hyperemesis. The presence of a fever is likewise more suggestive of an inflammatory process. A repeat evaluation of the patient should occur in a timely fashion (4 – 6 hours) if an inflammatory process is suspected. DIAGNOSTIC TESTS
The laboratory evaluation of the patient is important to clarify the diagnosis and obtain an impression of the severity of the disease. Patients with only mild nausea and vomiting will often respond to simple hydration and supportive care. Extensive laboratory work may not be required. With more clinically significant disease, more thorough investigations are warranted. Although an elevated white blood cell (WBC) count occurs physiologically during pregnancy, a total WBC count greater than
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TABLE 2
Evaluation of Hyperemesis Gravidarum Laboratory studies Complete blood count Urinalysis (specific gravity, ketones, WBCs) Urine for culture and sensitivity Urine drug screen Electrolytes (sodium, potassium, chloride, bicarbonate) Amylase Lipase Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) BUN Creatinine Bilirubin TSH Free T3 and T4 Free thyroxine index Radiologic studies Obstetric ultrasonography (abdominal and/or vaginal as warranted) Computed axial tomography (CT) scan used if specific physical findings warrant evaluation Magnetic resonance imaging (MRI) scan used if specific physical findings warrant evaluation
15,000 and a shift to the left (increased neutrophil count) suggests an inflammatory process. Medical consultation is advisable with the finding of significant aberrations in laboratory studies. Recommended diagnostic studies are summarized in Table 2. Judicious selection should be made, considering the need for clinical information and medical cost. For the patient who is severely dehydrated, attention should be paid to blood chemistries that may suggest the need for supplementation particularly of potassium and chloride. The results of such diagnostic studies will indicate whether further medical intervention will be necessary. An obstetric ultrasonogram should be performed if there are no recent data to rule out multiple gestation or trophoblastic disease that may be contributing factors in the patient’s clinical condition. Such diagnostic studies should be selectively ordered, depending on the clinical circumstances and likely differential diagnosis. Any physical, laboratory, or radiologic finding(s) that indicate the presence of pathologic condition should immediately be called to the attention of medical colleagues so as to initiate prompt therapeutic interventions. INITIAL MANAGEMENT
Initial management of patients with HG includes diet modification with avoidance of foods known to be irritating to the individual, wet-to-dry nutrients (sherbet, broth, gelatin, to dry crackers, toast), and various drug regimens. The use of pyridoxine (vitamin B6) (20) has 460
been advocated, and its efficacy has been demonstrated in clinical trials (20,21). Pyridoxine was combined with doxylamine succinate and dicyclomine in Bendectin, a previously popular antiemetic for pregnancy. Although approved by the Food and Drug Administration (FDA), Merrill National Laboratories voluntarily withdrew the drug from the market in 1982 because of intense litigation fears. This action was taken despite the fact that there was no evidence to support the alleged teratogenic claims against the drug (22). Of note, the rate of hospitalization for severe nausea and vomiting of pregnancy increased by a factor of two in the United States and Canada subsequent to its removal (23). Outpatient therapy has included the use of many of the phenothiazines either orally or by suppository. The initial management of nausea and vomiting in pregnancy is clearly within the CNM/CM’s scope of practice. Correcting mild dehydration, when the woman is able to retain some liquids, can be accomplished on an outpatient basis along with intermittent infusion of D5 and lactated Ringer’s solution. The addition of a parenteral antiemetic agent may help control nausea and allow for prompt discharge from the ambulatory or outpatient setting. With persistent symptoms, progressive weight loss, and/or abnormalities in laboratory studies, medical comanagement and hospitalization is often required (see Table 3). Weight loss (greater than 5% of body weight), persistent ketonuria, and metabolic disturbances (electrolytes, liver function disturbances, thyroid abnormalities) all require physician consultation and collaborative management; medical referral and follow-up may be warranted when conservative management (hydration, antiemetics) fails to relieve the nausea and vomiting of hyperemesis and/or electrolyte imbalance in a timely fashion. The role of the physician in determining the treatment plan increases with the severity of the symptoms. The physician should primarily manage the patient with hyperemesis to correct metabolic disturbances and restore nutritional balance. The midwife should provide emotional and psychological support to the patient and family in this highly stressful time. As the clinical condition improves, the midwife may resume the role of primary care provider or may continue to comanage the pregnancy. Hospitalization may be required when home and outpatient therapies are unsuccessful in stabilizing the patient from a metabolic perspective. With hospitalization, parenteral pharmacologic agents will usually be used. Recently, a regimen of continuous intravenous (IV) droperidol and bolus IV diphenhydramine was shown to be more effective than traditional intermittent therapy in terms of duration of hospital stay and readmission rate (24) (see Table 4). Parenteral ondansetron has been tried in a small group of patients with HG (25). Unfortunately, it proved no
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TABLE 3
Criteria for Management of Hyperemesis Gravidarum Independent Midwifery Management
Collaborative Management
Timing Severity
First Trimester Mild, no weight loss, fluid tolerance, first line medications
Beyond 14 weeks’ gestation Unresponsive to first line drugs, no tolerating fluids
Laboratory
Normal laboratory results
Ketonuria, increasing BUN, creatinine, mild hypokalemia
Weight status
Negligible weight loss (⬍5 lb) In remission
Loss greater than 5–10 lb
Concurrent medical disorders (diabetes, GI disorders)
more effective than promethazine in controlling the patient symptoms. Safari et al (26) have recently used a protocol using oral methylprednisolone, an agent that has been reported as successful in improving the patient’s clinical condition and decreasing hospital readmission for hyperemesis compared with promethazine. Other data using prednisolone for up to 10 weeks have demonstrated that it is effective in the control of hyperemesis (27). When pharmacologic efforts have proven unsuccessful and nutrition must be established, Hsu et al (28) demonstrated, in a small series, the value of enteral feeding with the use of an 8-F Dobbhoff nasogastric feeding tube. This allowed the progressive increase in nutritional support until caloric needs were met, and continuation of the therapy was effectively carried out at home. Total parenteral nutrition may become necessary in those cases resistant to therapies discussed. This can be successfully accomplished within hospital (29) and home environments (30). The use of home therapy has been demonstrated to be efficacious, safe, and economically advantageous. Naef et al (31) showed a favorable total cost differential for daily care ($708 vs $2,701) for patients treated at home with the same therapy as in hospital. The psychological aspects of nausea and vomiting of pregnancy have been reviewed in the literature (9). Controversy exists as to the impact of such factors. In some cases, psychosocial factors that may influence nausea and vomiting in pregnancy include unwanted pregnancy, conflict with the significant partner, low socioeconomic status, generalized anxiety or depressive episodes, and lost wages or loss of control at home because of debilitation. Sensitivity to such influencing factors is critical and may facilitate a more prompt recovery. Brief, focused psychotherapy in conjunction
If likely relevant to care
Hospitalization and Medical Management Unremitting and persistent Unresponsive to home care, abnormal laboratory results, significant weight loss Severe ketonuria, acidosis, hypokalemia, elevated liver function tests and/or amylase and lipase Weight loss above 5% of body weight If in exacerbation
with medical therapy may be indicated in cases of severe hyperemesis. Among the more serious complications of hyperemesis is the potential for Wernicke’s encephalopathy, a clinical triad of ophthalmoplegia, gait ataxia, and confusion. This condition is primarily a deficiency of thiamin (vitamin B1). Persistent disease requires replacement of this vitamin and others in the B complex, including vitamin B6 and B12 (32). Other reported adverse maternal side effects have included spontaneous pneumomediastinum (33), coagulopathy resulting from vitamin K deficiency (34), jaundice (35), central pontine myelinolysis, and death (36). Because of the various roles women fill, medical management, even when coupled with psychological support or therapy, may not address all of the needs facing women with hyperemesis. Ancillary stressors such as childcare, housework, meal preparation, and home organization must also be considered. The care provider should explore with the woman and her family the resources that are available to her for assistance in these areas. Modification of work schedules, time off from work, and explanation of the condition to employers will facilitate the return to work of the individual with hyperemesis who is employed outside of the home. All care providers must have sensitivity for the impact of lost work on income, job security, health insurance, and other employee benefits to the affected patient so that a reassuring and supportive atmosphere is maintained. Outside community resources can be accessed when appropriate. Many “alternative” or nonpharmacologic remedies have been thought to achieve measures of success in controlling hyperemesis in pregnancy (37). The therapies are as diverse as the providers who recommend them. Acupressure and acupuncture (38,39), gingerroot (40), and hypnosis or hypnotherapy (41) are among modalities
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TABLE 4 (45– 47)
Pharmacologic Regimens for the Treatment of Hyperemesis Gravidarum Parenteral Therapy: Intravenous fluids (D5 & 1/2NS) with additional K⫹ as necessary; total parenteral nutrition with appropriate additives, including K⫹ and multivitamins, particularly thiamin, B6 and B12. Pharmacologic Therapy Drug (Commercial Name)
FDA Risk Category
Dose
Vitamin B6 (pyridoxine) Promethazine (Phenergan) Droperidol (Inapsine) Combination therapy of droperidol and diphenhydramine
A C
30 mg qd 25 mg po/rectal suppositories q4–6h
CM CM
0.625–1.25 mg IV/IM 25 mg in 500 mL NS @ 1 mg (20 mL)/h IV and 50 mg IV q6h (begin before droperidol)
Prochlorperazine (Compazine)
C
Trimethobenzamide (Tigan)
C
5–10 mg PO 3–4⫻/day 2.5–10 mg Not to exceed 40 mg/d Rectal suppository 25 mg bid 250 mg PO tid to qid 200 mg tid to qid or by suppository
Hydroxyzine (Vistrail) (Atarax)
C
25–100 mg q4–6h IM/PO
Metoclopramide (Reglan)
BM
10 mg PO qid Continuous subcutaneous infusion
Ondansetron (Zofran)
BM
4 mg (over 2–5 min) IV/IM 8 mg PO q8h
Methyl Prednisolone (Medrol) Ginger root
B
Multidose regimen (21) 250 mg bid
Major Side Effects/ Contraindications* None known Drowsiness Extrapyramidal signs† Extrapyramidal symptoms Akathisia (restlessness, hyperactivity, anxiety) Dystonia Dizziness Extrapyramidal symptoms Neuroleptic signs Tarditive dyskinesia Extrapyramidal symptoms Hepatotoxicity Blood dyscrasias Possible anomalies with first trimester use: potentiates, narcotics, barbiturates Involuntary motor activity Mental depression Tarditive dyskinesa Acute dystonic reactions Headache Dizziness Musculoskeletal pain Drowsiness Fluid retention Change in carbohydrate tolerance Increased salivation Not to be taken if gallstones present
* A full review of the side effects and contraindications of any agent administered in pregnancy should be undertaken if the provider is not familiar with the pharmacologic agent being dispensed. † Diphenhydramine (Benedryl) is the specific antidote for the extrapyramidal manifestations seen on occasion with the phenothiazines.
discussed in the literature to control or improve hyperemesis. Acupuncture was deemed efficacious in a review of 12 randomized placebo controlled trials as “an effective antiemetic technique” (42). Other investigators (43,44) have found the use of acupressure at the PC-6 point (on the flexor tendon) on the medial aspect of both arms to be beneficial (39). Improvement in nausea, but not vomiting, was demonstrated by these studies (43,44). In a review of the literature addressing several alternative therapies, Murphy (37) noted that some of these studies are flawed in design, selection bias, and face difficulties with comparison to control populations. In her review, it was believed that the best-studied “alternative” remedy was acupressure, which may afford some relief; ginger and pyridoxine were also thought to be beneficial. Care should be exercised in adopting any
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“new” therapy without reasonable demonstration of success based on appropriate investigations. CASE STUDY
M.S. is a 23-year-old gravida 1 para 0 who called her midwife one evening when she was at 8 weeks’ gestational age. Her complaint was nausea and vomiting for the last 24 hours. She was advised to try sips of clear liquids through the evening and to come to the office in the morning if the vomiting persisted. The next morning M.S. came to the office for evaluation. She continued to experience nausea and intermittent emesis. Her weight was 142 pounds, a reduction of 2 pounds from her initial evaluation examination 2 weeks earlier. Her vital signs were normal, but urine specific
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gravity was 1.030 and showed a trace of ketones. The midwife ruled out other potential underlying diseases by a complete history and physical examination and initiated treatment for nausea and vomiting of pregnancy. An IV of D5LR with 50 mg of Phenergan added was administered in the office. After the infusion of 1 L of fluids, M.S. stated that she was much better and was sent home after receiving counseling regarding diet modification and fluid recommendations. She was also given a prescription for Phenergan suppositories (25 mg) to use every 6 hours as needed for nausea. She was advised to take vitamin B6 supplements (50 mg) po twice daily. One week later, M.S. called again to complain of nausea and vomiting. She stated the Phenergan was no longer relieving her symptoms. She had lost an additional 5 pounds, and her urine was very concentrated. A later office check showed 2⫹ ketones. She had tried to use a wet to dry diet, but continued to experience vomiting several times a day. The midwife arranged to have M.S. admitted to the hospital’s antepartum unit for a short stay. At that time, an ultrasonogram was performed, which confirmed an intrauterine pregnancy at 9 weeks’ gestational age. A complete blood count and chemistry panel were obtained, and values were normal except for a potassium level of 3.3 mmol/L (normal range, 3.5–5.3 mmol/L). A urinanalysis showed a high specific gravity and 2⫹ ketones. An IV of D5LR was started along with 0.625 mg of droperidol IV push. One ampule of multivitamin was added to the first liter of IV fluids. The next afternoon, M.S. was tolerating a bland diet, her urine was negative for ketones, and she was discharged with a prescription for Zofran (8 mg) to be taken every 8 hours for nausea. Five days after discharge, at almost 10 weeks’ gestation, M.S. returned to the midwifery service. She had lost an additional 6 pounds, for a total of 13 pounds of weight loss. Urine dipstick indicated 3⫹ ketones. She could not hold down any food and only retained minimal liquids for 2 days. Her potassium was 3.0 mEq/mL. Her hemoglobin was 14.8 g/dL. The midwife recommended hospital admission and contacted the consulting physician for medical evaluation. The medical management included an initial dose of diphenhydramine, 50 mg IV, to be continued every 6 hours; Droperidol, 25 mg in 500mL normal saline, was also started at 1 mg (20mL)/hour IV. Arrangements were made for the placement of a central venous line for total parenteral nutrition. M.S. was allowed nothing by mouth for 2 days, when she requested the initiation of a dry diet. Once established, there was some improvement, and she was discharged to home care with the central line in place. Both the obstetric consultant and the midwife saw her over the next 3 weeks by which time she had resumed a nearly normal diet. After 1 week without nausea or vomiting, the central line was removed, and the manage-
ment of her care was resumed fully by the midwife. The pregnancy progressed to a term delivery without complications. In summary, despite the homeopathic and pharmacologic regimens advocated to date, no single therapeutic approach has consistently proven efficacious in the treatment of HG. The midwife and medical consultant must remain clinically diligent in their evaluation, active in their therapeutic collaboration, and mutually supportive during the patient’s time in recovery. Only by such cooperative use of respective expertise can optimal patient care be rendered and a successful outcome achieved. CONCLUSION
HG is the extreme state of the common complaint of nausea and vomiting in pregnancy. Recognition of its onset and prompt intervention requires midwifery care and support. Prompt use of midwifery and medical resources will minimize long-term care and lead to restitution of normal function and life activity for the afflicted gravida. Dynamic collaborative activity on the part of the midwife and physician will afford the patient who has hyperemesis the optimum of diagnostic and therapeutic assistance. REFERENCES 1. Signorello LB, Harlow BL, Wang S, Erick MA. Saturated fat intake and the risk of severe hyperemesis gravidarum. Epidemiology 1998;9: 636 – 40. 2. Vellacott ID, Cooke EJ, James CE. Nausea and vomiting in early pregnancy. Int J Obstet Gynecol 1988;27:57– 62. 3. Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract 1993;43:245– 8. 4. Scott LD, Kozinetz C, Gonik B. Gastrointestinal function in pregnancy [abstract]. Gastroenterology 1986;90:1624. 5. Abell TL, Riely CA. Hyperemesis gravidarum. Gastroenterol Clin North Am 1992;21:835– 49. 6. Klebanoff MA, Koslowe PA, Kaslow R, Rhoads GG. Epidemiology of vomiting in early pregnancy. Obstet Gynecol 1985;66:612– 6. 7. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol 1998; 41:597– 605. 8. Wald NJ, Cuckle HS. Biochemical screening. In: Brock DJH, Rodek CH, Ferguson-Smith MA, eds. Prenatal diagnosis and screening. Edinburgh: Churchill Livingstone, 1992. 9. Deuchar N. Nausea and vomiting in pregnancy: a review of the problem with particular regard to psychological and social aspects. Br J Obstet Gynaecol 1995;102:6 –10. 10. Frigo P, Lang C, Reisenberger K, Kolbl H, Hirschl AM. Hyperemesis gravidarum associated with Helicobacter pylori seropositivity. Obstet Gynecol 1998;91:615–7. 11. Goodwin TM, Hershman JM, Cole L. Increased concentration of the free -subunit of human chorionic gonadotropin in hyperemesis gravidarum. Acta Obstet Gynecol Scand 1994;73:770 –2. 12. Goodwin TM, Mestman J. Transient hyperthyroidism of hyperemesis gravidarum. Cont Ob-Gyn 1996;41(6):65–78. 13. Price A, Davies R, Heller SR, Milford-Ward A, Weetman AP. Asian
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women are at increased risk of gestational thyrotoxicosis. J Clin Endocrinol Metab 1996;81:1160 –3. 14. Mori M, Amino N, Tamaki H. Morning sickness and thyroid function in normal pregnancy. Obstet Gynecol 1988;72:355–9. 15. Mestman JH. Hyperthyroidism in pregnancy. Endocrinol Metab Clin North Am 1998;27:127– 49. 16. Gross S, Librach C, Cecutti A. Maternal weight loss associated with hyperemesis gravidarum: a predictor of fetal outcome. Am J Obstet Gynecol 1989;160:906 –9. 17. Hallak M, Tsalamandris K, Dombrowski M, Isada N, Pryde PG, Evans MI. Hyperemesis gravidarum: effects on fetal outcome. J Reprod Med 1996;41:871– 4. 18. Tsang IS, Katz VL, Wells SD. Maternal and fetal outcomes in hyperemesis gravidarum. Int J Gynaecol Obstet 1996;55:231–5. 19. Varney H. Varney’s midwifery. Boston: Blackwell Scientific Publications, 1997. 20. Vutyavanich T, Wongtrangan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized double blind placebo-controlled trial. Am J Obstet Gynecol 1995;173:881– 4. 21. Sahakian V, Rouse D, Sipes S. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized double blind placebo controlled trial. Obstet Gynecol 1991;78:33– 6. 22. Shapiro S, Heinonen OP, Siskind V, Kaufman DW, Monson RR, Slone D. Antenatal exposure to doxyalamine succinate and dicyclomine hydrochloride (Bendectin) in relation to congenital malformations, perinatal mortality rate, birth weight and intelligence quotient score. Am J Obstet Gynecol 1997;128:480 –5. 23. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med 1998;338:1128 –37. 24. Nagotte MP, Briggs GG, Towers CV, Asrat T. Droperidol and diphenhydramine in the management of hyperemesis gravidarum. Am J Obstet Gynecol 1996;174:1801–5. 25. Sullivan CA, Johnson CA, Roach H, Martin RW, Stewart DK, Morrison JC. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol 1996;174:1565– 8. 26. Safari HR, Fassett MJ, Souter IC, Alsulyman OM, Goodwin TM. The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double blind, controlled study. Am J Obstet Gynecol 1998;179:921– 4. 27. Taylor R. Successful management of hyperemesis gravidarum using steroid therapy. Q J Med 1996;89:103–7. 28. Hsu JJ, Clark-Glena R, Nelson DK, Kim CH. Nasogastric enteral feeding in the management of hyperemesis gravidarum. Obstet Gynecol 1996;88:343– 6. 29. Newman V, Fullerton JT, Anderson PO. Clinical advances in the management of severe nausea and vomiting during pregnancy. J Obstet Gynecol Neonatal Nurs 1993;22:483–90.
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30. Cowan MJ. Hyperemesis gravidarum: implications for home care and infusion therapies. J Intraven Nurs 1996;19:46 –58. 31. Naef RW, Chauhan SP, Roach H, Roberts WE, Travis KH, Morrison JC. Treatment of hyperemesis gravidarum in the home: an alternative to hospitalization. J Perinatol 1995;15:289 –92. 32. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol 1998; 41:597– 605. 33. Gorbach JS, Counselman FL, Mendelson MH. Spontaneous pneumomediastinum secondary to hyperemesis gravidarum. J Emerg Med 1997;15:639 – 40. 34. Robinson JN, Banerjee R, Thiet MP. Coagulopathy secondary to vitamin K deficiency in hyperemesis gravidarum. Obstet Gynecol 1998; 92:673–5. 35. Orazi G, Dufour PH, Puech F. Jaundice induced by hyperemesis gravidarum. Int J Gynaecol Obstet 1998;61:181–3. 36. Nelson-Piercy C. Treatment of nausea and vomiting in pregnancy: when should it be treated and what can be safely taken? Drug Safety 1998;19:155– 64. 37. Murphy PA. Alternative therapies for nausea and vomiting of pregnancy. Obstet Gynecol 1998;91:149 –55. 38. Belluomini J, Litt R, Lee K, Katz M. Acupressure for nausea and vomiting of pregnancy: a randomized blinded study. Obstet Gynecol 1994; 84:245– 8. 39. Hoo JJ. Acupressure for hyperemesis gravidarum [letter] Am J Obstet Gynecol 1997;176:1395–7. 40. Fischer-Rasmussen W, Kjuer S, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1990;38:19 –24. 41. Baram DA. Hypnosis in reproductive health care: a review and case reports. Birth 1995;22:37– 42. 42. Vickers AJ. Can acupuncture have specific effects on health? A systematic review of acupuncture antiemesis trials. J R Soc Med 1996;89: 303–11. 43. Belluomini J, Litt RC, Lee K, Katz M. Acupressure for nausea and vomiting of pregnancy: a randomized blinded study. Obstet Gynecol 1994; 84:245– 8. 44. Hyde E. Acupressure therapy for morning sickness: a controlled clinical trial. J Nurse Midwifery 1989;34:171– 8. 45. Briggs GG, Freeman RK, Yaffe SY. Drugs in pregnancy and lactation. 5th ed. Baltimore: Williams & Wilkins, 1998. 46. Physician’s Desk Reference. 54th ed. Montvale, NJ: Medical Economics, 2000. 47. Briggs GG. A guideline for treating hyperemesis gravidarum. Contemp Ob/Gyn 1997;April:70 –9.
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CNM, MSN
and J. Patrick Lavery,
ABSTRACT Hyperemesis gravidarum is an infrequent, yet significant, maternal complication of pregnancy. Beginning with the frequently experienced nausea and vomiting of pregnancy, symptoms can progress to hyperemesis, a debilitating condition affecting maternal and fetal well-being. A basic understanding of the pathophysiology of the disease process and an awareness of the therapeutic interventions that are available will facilitate midwifery planning for either the collaborative care or the potential referral to medical management, both of which may be required with this clinical entity. The diagnosis and initial management of hyperemesis is within the purview of midwifery care. As certain critical features of duration and severity evolve, medical collaboration and ultimate hospitalization may be required. For those few individuals requiring the most intense level of care, the critical support and encouragement afforded by midwifery participation will contribute to timely resolution of this debilitating condition. This article discusses the continuum from differential diagnosis to ultimate care of the woman who has excessive nausea and vomiting of pregnancy. Collaboration among health care providers will allow all to exercise their respective skills in achieving the optimum in safe therapy and support for their patients. J Midwifery Womens Health 2000;45:457– 64 © 2000 by the American College of Nurse-Midwives. INTRODUCTION
Nausea and vomiting in early pregnancy is common, affecting a significant number of all women during pregnancy. When it reaches the clinical picture of a metabolic disturbance with weight loss, alkalosis, dehydration, hypokalemia, and altered nutritional status, the diagnosis of hyperemesis gravidarum (HG) is made. More than 50,000 pregnant women are hospitalized each year in the United States for HG for an average of 4 days (1). The criteria for the diagnosis have ranged from the arbitrary need for hospitalization to a metabolic disturbance associated with persistent vomiting, large ketonuria, and loss of more than 5% of body weight. Resolution is usually achieved by midpregnancy. However, in the interim, this condition may pose a diagnostic and therapeutic challenge for the care provider and incalculable misery for the afflicted gravida. This article discusses the physiology, differential diagnosis, and therapeutic aspects of HG. The progression from midwifery diagnosis and evaluation to the comple-
Address correspondence to Joan Slager, CNM, MSN, Bronson Medical Office Pavilion, 601 John Street, Suite M-351, Kalamazoo, MI 49007.
MD
ment of medical interventions illustrates the critical roles played by the respective providers to achieve a successful outcome. It challenges certified nurse-midwives (CNMs)* and certified midwives (CMs)* who must frequently evaluate the patient, initiate appropriate diagnostic studies, and facilitate the use of a broad armamentarium of pharmacologic agents and nonpharmacologic interventions for therapy. The use of midwifery* skills in clinical diagnosis and support is essential for the patient so affected. The medical resources that are often implemented will be reviewed in this discussion so as to delineate the parameters for initiating collaborative care or primary medical management. Ongoing midwifery participation in the care of the patient often contributes to a more satisfactory outcome as medical therapy is implemented. The impact of nausea, vomiting, and ultimately, hyperemesis cannot be overstated. In one study, nearly 50% of employed women believed that their work efficiency was affected by pregnancy-related nausea and vomiting and as many as 25% required time off (2). In a similar review, Gadsby et al (3) found that of 206 pregnant women in paid employment, 35% spent an average of 62 hours away from their job. The personal and social impact of this clinical disturbance is clearly quite significant; thus, midwives* should be prompt in the assessment, management, and initiation of therapy for this complex and occasionally progressive malady of gestation. PHYSIOLOGY
Reports indicate that 66 –70% of gravid women have nausea and that 18 – 44% experience significant vomiting in pregnancy (3,4). Nausea and vomiting of pregnancy typically begin at 4 – 6 weeks of gestation, reaching their most severe degree at 8 –12 weeks and abating by 20 weeks. The diagnosis of “hyperemesis” with associated metabolic disturbances occurs in 3.3–10 per 1,000 pregnancies (5). Clinical conditions that show a statistical association with hyperemesis diagnosis include increased body weight, nulliparity, multiple gestation, gestational * CNMs/CMs and midwives as used herein refer to those midwifery practitioners who are certified by the American College of Nurse-Midwives (ACNM) or the ACNM Certification Council, Inc.; midwifery refers to the profession as practiced in accordance with the standards promulgated by the ACNM.
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trophoblastic disease, a history of previous hyperemesis, and a pregestational high-fat diet (72 g/day), particularly in saturated fats (1). Hyperemesis is seen less frequently in smokers and women older than 35 years of age (5,6). Fetal factors associated with hyperemesis include triploidy (partial mole), trisomy 21, and hydrops fetalis (7). The reason for such associations is not clear. Aneuploidy (particularly trisomy 21) has been associated with elevated human chorionic gonadotropin (hCG) levels, (8); however, the association between hyperemesis and rising total hCG levels, once thought significant, has been disputed by Abel and Riely (5). The specific cause of hyperemesis is unknown. However, certain clinical factors have been suggested as contributors to the pathophysiology of hyperemesis; these include increased sensitivity of the chemoreceptor trigger zone (CTZ); disturbances in gastric motility (similar to diabetic gastroparesis) mediated by progesterone; and the influence of pregnancy-related hormonal change, including hCG, thyroxin, and cortisol. Psychological and social factors have been likewise implicated as has a lack of (less than 12 years) formal education (9). Frigo et al (10) have described a strong association with the presence of Helicobacter pylori IgG antibodies (90.5%) in patients with HG as opposed to 46.5% in the control population. In an extensive review of the various causes of hyperemesis, Abell and Riely (5) found no substantial or consistent factor among the multiple proposed causes of this significant clinical problem. Recently, Goodwin et al (11,12) have reported the finding of significantly higher concentrations of total hCG and the free  subunit of hCG in women with true hyperemesis compared with controls. A greater predilection to HG has been seen in Asian populations (13); this has been associated with specific isoforms of hCG and hyperthyroidism, suggesting that genetically determined predilections to HG exist, at least in this studied population. Mori et al (14) have demonstrated the thyroid-stimulating effect of hCG leading to an increase in free thyroxine (T4) and decrease in thyroid-stimulating hormone (TSH). This “biochemical” appearance of hyperthyroidism should not be confused with actual Graves’ disease. Resolution of the biochemical picture will occur,
Joan Slager is director of nurse-midwifery for the Bronson Women’s Service at Bronson Methodist Hospital, Kalamazoo, Michigan. She received her nurse-midwifery certificate from the community-based Nurse-Midwifery Education Program at the Frontier School of Midwifery and Family Nursing in 1991 and her Masters of Science in Nursing from Case Western Reserve University in 1993. J. Patrick Lavery is a perinatologist at Bronson Methodist Hospital, Kalamazoo, Michigan. He also serves as Bronson’s Medical Director of Women’s Reproductive Services. Dr. Lavery is a professor of obstetrics, gynecology, and reproductive medicine at Michigan State University, East Lansing, Michigan.
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and the hCG levels decline as symptoms abate generally after 16 –18 weeks’ gestation. Continued clinical problems and lack of remission of the symptoms may warrant further evaluation. Goodwin and Mestman (12) have shown a significant correlation between the severity of hyperemesis and transient disturbances in thyroid function, as measured by the T4 index and suppressed thyrotropin. Although biochemical levels may measure in the hyperthyroid range, this syndrome generally does not require antithyroid medication and resolves spontaneously with the diminution of symptoms (15). To facilitate differentiation between true thyroid disease and hyperemesis, the finding of a TSH level of 0.1 mU/L (lower than seen with hyperemesis), an elevated FT4 and/or FT3 suggest coexistent hyperthyroidism.
FETAL OUTCOMES
Even with the diagnosis of hyperemesis, the rate of pregnancy loss has been reported lower than expected in the general population (5). Although it would at least suggest that the metabolic disturbances incurred with the process do not have significant adverse fetal effects, Gross et al (16) reviewed pregnancy outcome from a fetal growth perspective and reported that fetal growth retardation was more prevalent (30% v 6%) in the population experiencing more than 5% weight loss when hyperemesis was present in early pregnancy. They suggested that weight loss and metabolic disturbance in early gestation may be a distinct entity placing the fetus at risk for subsequent growth problems. Other studies (17,18) have looked at later pregnancy outcome and have reported more favorable results for the fetus after early pregnancy hyperemesis. Hallak et al (17) reviewed data on 40 patients with mild hyperemesis and 98 with severe hyperemesis. When compared with the 12,335 nonaffected gravidas who served as controls, there was no difference when fetal growth, prematurity rates, incidence of congenital malformations, newborn parameters of Apgar score, and NICU admissions were considered. Tsang et al (18) also reported a similarly favorable outcome in their population of 193 women with HG. These women represented 1.5% of their total population (13,053) in which there were similar outcomes when mean birth weights, incidences of prematurity, Apgar scores, perinatal mortality, and incidences of anomalies were compared. In summary, research related to the long-term consequences of hyperemesis for the fetus has not thus far resolved all of the issues; however, there is good supporting information suggestive of a favorable fetal prognosis despite hyperemesis in early gestation.
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DIFFERENTIAL DIAGNOSIS
When a pregnant woman with hyperemesis initially is seen for midwifery care, it is important to promptly assess the patient’s clinical picture and initiate appropriate diagnostic studies. Underlying diseases should be ruled out. Initiation of conservative pharmacologic therapy, dietary counseling, and psychological support will be effective in most cases. A detailed history should be taken when a woman has nausea and vomiting in pregnancy. A previous pregnancy afflicted by hyperemesis is often a clue to recurrence; however, primary medical and surgical conditions must be considered before such a conclusion can be drawn. Elements of the history should include potential for acute problems such as food poisoning, diet history, the frequency of vomiting episodes, relationship of the vomiting to intake, the nature of the vomitus, and psychological factors precipitating the vomiting, if any exist. Sensitivity to food odors is more characteristic of hyperemesis than other medical causes of significant vomiting, whereas the presence of fever, chills, or localized pain is more suggestive of an inflammatory process. The history of any medical condition warrants further attention. Conditions such as chronic pancreatitis, Crohn’s disease, and other inflammatory bowel disease may be exacerbated in pregnancy. Assessment for weight loss is also an essential part of the diagnostic work-up. The continued evaluation of a patient with HG must take into consideration pregnancy-related conditions and other systemic processes (see Table 1). A prior medical history of gastrointestinal (GI) or renal problems may be significant. Critical diagnoses to eliminate are inflammatory GI disorders (eg, appendicitis, cholecystitis, and pancreatitis), pregnancy-related problems (multiple gestation, trophoblastic disease), and other systemic medical disorders (diabetes, acute renal disease, pyelonephritis, and metabolic disorders such as hyperthyroidism and hyperparathyroidism). Unless a specific diagnosis of hyperthyroidism is made, antithyroid hormonal therapy is not required, because both hyperemesis and chemical hyperthyroidism appear to resolve with the passage of time (5). The physical examination should be complete and comprehensive observing carefully for signs of dehydration. In addition to monitoring the vital signs, assessment should include assessment of the lips and mucous membranes, the turgor of the skin, urinary output, and concentration of the urine. This evaluation will give some indication of the presence and severity of any dehydration and will dictate the degree of intervention that is warranted. Abdominal examination should include assessment of bowel sounds, point tenderness, and organomegaly (19). In the case of hyperemesis, abdominal findings are usually mild and nonspecific. Localizing
TABLE 1
Considerations in the Differential Diagnosis of Hyperemesis Gravidarum Pregnancy-related Multiple gestation Trophoblastic disease Fetal anomalies/aneuploidy (see text) Genitourinary disorders Pylonephritis Uremia Kidney stones Degenerating leiomyomata Gastrointestinal disease Biliary tract (gallbladder) disease Hepatitis Pancreatitis Appendicitis Gastroenteritis Peptic ulcer disease Gastroesophageal reflux disease Intestinal obstruction Metabolic problems Hyperthryoidism (thyrotoxicosis) Hyperparathyroidism Diabetic ketoacidosis Porphyria Addison’s disease Central nervous system disorders Pseudotumor cerebri Brain tumor Neuropsychiatric diagnoses Migraine headache Vestibular nerve stimulation Increased intracranial pressure Meningeal irritation
symptoms are more suggestive of specific disease entities such as appendicitis and pyelonephritis. On physical examination, eliciting point tenderness, rebound pain, and finding ileus with tympanitic percussive findings and hypoactive bowel sounds are more suggestive of an inflammatory disease than hyperemesis. The presence of a fever is likewise more suggestive of an inflammatory process. A repeat evaluation of the patient should occur in a timely fashion (4 – 6 hours) if an inflammatory process is suspected. DIAGNOSTIC TESTS
The laboratory evaluation of the patient is important to clarify the diagnosis and obtain an impression of the severity of the disease. Patients with only mild nausea and vomiting will often respond to simple hydration and supportive care. Extensive laboratory work may not be required. With more clinically significant disease, more thorough investigations are warranted. Although an elevated white blood cell (WBC) count occurs physiologically during pregnancy, a total WBC count greater than
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TABLE 2
Evaluation of Hyperemesis Gravidarum Laboratory studies Complete blood count Urinalysis (specific gravity, ketones, WBCs) Urine for culture and sensitivity Urine drug screen Electrolytes (sodium, potassium, chloride, bicarbonate) Amylase Lipase Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) BUN Creatinine Bilirubin TSH Free T3 and T4 Free thyroxine index Radiologic studies Obstetric ultrasonography (abdominal and/or vaginal as warranted) Computed axial tomography (CT) scan used if specific physical findings warrant evaluation Magnetic resonance imaging (MRI) scan used if specific physical findings warrant evaluation
15,000 and a shift to the left (increased neutrophil count) suggests an inflammatory process. Medical consultation is advisable with the finding of significant aberrations in laboratory studies. Recommended diagnostic studies are summarized in Table 2. Judicious selection should be made, considering the need for clinical information and medical cost. For the patient who is severely dehydrated, attention should be paid to blood chemistries that may suggest the need for supplementation particularly of potassium and chloride. The results of such diagnostic studies will indicate whether further medical intervention will be necessary. An obstetric ultrasonogram should be performed if there are no recent data to rule out multiple gestation or trophoblastic disease that may be contributing factors in the patient’s clinical condition. Such diagnostic studies should be selectively ordered, depending on the clinical circumstances and likely differential diagnosis. Any physical, laboratory, or radiologic finding(s) that indicate the presence of pathologic condition should immediately be called to the attention of medical colleagues so as to initiate prompt therapeutic interventions. INITIAL MANAGEMENT
Initial management of patients with HG includes diet modification with avoidance of foods known to be irritating to the individual, wet-to-dry nutrients (sherbet, broth, gelatin, to dry crackers, toast), and various drug regimens. The use of pyridoxine (vitamin B6) (20) has 460
been advocated, and its efficacy has been demonstrated in clinical trials (20,21). Pyridoxine was combined with doxylamine succinate and dicyclomine in Bendectin, a previously popular antiemetic for pregnancy. Although approved by the Food and Drug Administration (FDA), Merrill National Laboratories voluntarily withdrew the drug from the market in 1982 because of intense litigation fears. This action was taken despite the fact that there was no evidence to support the alleged teratogenic claims against the drug (22). Of note, the rate of hospitalization for severe nausea and vomiting of pregnancy increased by a factor of two in the United States and Canada subsequent to its removal (23). Outpatient therapy has included the use of many of the phenothiazines either orally or by suppository. The initial management of nausea and vomiting in pregnancy is clearly within the CNM/CM’s scope of practice. Correcting mild dehydration, when the woman is able to retain some liquids, can be accomplished on an outpatient basis along with intermittent infusion of D5 and lactated Ringer’s solution. The addition of a parenteral antiemetic agent may help control nausea and allow for prompt discharge from the ambulatory or outpatient setting. With persistent symptoms, progressive weight loss, and/or abnormalities in laboratory studies, medical comanagement and hospitalization is often required (see Table 3). Weight loss (greater than 5% of body weight), persistent ketonuria, and metabolic disturbances (electrolytes, liver function disturbances, thyroid abnormalities) all require physician consultation and collaborative management; medical referral and follow-up may be warranted when conservative management (hydration, antiemetics) fails to relieve the nausea and vomiting of hyperemesis and/or electrolyte imbalance in a timely fashion. The role of the physician in determining the treatment plan increases with the severity of the symptoms. The physician should primarily manage the patient with hyperemesis to correct metabolic disturbances and restore nutritional balance. The midwife should provide emotional and psychological support to the patient and family in this highly stressful time. As the clinical condition improves, the midwife may resume the role of primary care provider or may continue to comanage the pregnancy. Hospitalization may be required when home and outpatient therapies are unsuccessful in stabilizing the patient from a metabolic perspective. With hospitalization, parenteral pharmacologic agents will usually be used. Recently, a regimen of continuous intravenous (IV) droperidol and bolus IV diphenhydramine was shown to be more effective than traditional intermittent therapy in terms of duration of hospital stay and readmission rate (24) (see Table 4). Parenteral ondansetron has been tried in a small group of patients with HG (25). Unfortunately, it proved no
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TABLE 3
Criteria for Management of Hyperemesis Gravidarum Independent Midwifery Management
Collaborative Management
Timing Severity
First Trimester Mild, no weight loss, fluid tolerance, first line medications
Beyond 14 weeks’ gestation Unresponsive to first line drugs, no tolerating fluids
Laboratory
Normal laboratory results
Ketonuria, increasing BUN, creatinine, mild hypokalemia
Weight status
Negligible weight loss (⬍5 lb) In remission
Loss greater than 5–10 lb
Concurrent medical disorders (diabetes, GI disorders)
more effective than promethazine in controlling the patient symptoms. Safari et al (26) have recently used a protocol using oral methylprednisolone, an agent that has been reported as successful in improving the patient’s clinical condition and decreasing hospital readmission for hyperemesis compared with promethazine. Other data using prednisolone for up to 10 weeks have demonstrated that it is effective in the control of hyperemesis (27). When pharmacologic efforts have proven unsuccessful and nutrition must be established, Hsu et al (28) demonstrated, in a small series, the value of enteral feeding with the use of an 8-F Dobbhoff nasogastric feeding tube. This allowed the progressive increase in nutritional support until caloric needs were met, and continuation of the therapy was effectively carried out at home. Total parenteral nutrition may become necessary in those cases resistant to therapies discussed. This can be successfully accomplished within hospital (29) and home environments (30). The use of home therapy has been demonstrated to be efficacious, safe, and economically advantageous. Naef et al (31) showed a favorable total cost differential for daily care ($708 vs $2,701) for patients treated at home with the same therapy as in hospital. The psychological aspects of nausea and vomiting of pregnancy have been reviewed in the literature (9). Controversy exists as to the impact of such factors. In some cases, psychosocial factors that may influence nausea and vomiting in pregnancy include unwanted pregnancy, conflict with the significant partner, low socioeconomic status, generalized anxiety or depressive episodes, and lost wages or loss of control at home because of debilitation. Sensitivity to such influencing factors is critical and may facilitate a more prompt recovery. Brief, focused psychotherapy in conjunction
If likely relevant to care
Hospitalization and Medical Management Unremitting and persistent Unresponsive to home care, abnormal laboratory results, significant weight loss Severe ketonuria, acidosis, hypokalemia, elevated liver function tests and/or amylase and lipase Weight loss above 5% of body weight If in exacerbation
with medical therapy may be indicated in cases of severe hyperemesis. Among the more serious complications of hyperemesis is the potential for Wernicke’s encephalopathy, a clinical triad of ophthalmoplegia, gait ataxia, and confusion. This condition is primarily a deficiency of thiamin (vitamin B1). Persistent disease requires replacement of this vitamin and others in the B complex, including vitamin B6 and B12 (32). Other reported adverse maternal side effects have included spontaneous pneumomediastinum (33), coagulopathy resulting from vitamin K deficiency (34), jaundice (35), central pontine myelinolysis, and death (36). Because of the various roles women fill, medical management, even when coupled with psychological support or therapy, may not address all of the needs facing women with hyperemesis. Ancillary stressors such as childcare, housework, meal preparation, and home organization must also be considered. The care provider should explore with the woman and her family the resources that are available to her for assistance in these areas. Modification of work schedules, time off from work, and explanation of the condition to employers will facilitate the return to work of the individual with hyperemesis who is employed outside of the home. All care providers must have sensitivity for the impact of lost work on income, job security, health insurance, and other employee benefits to the affected patient so that a reassuring and supportive atmosphere is maintained. Outside community resources can be accessed when appropriate. Many “alternative” or nonpharmacologic remedies have been thought to achieve measures of success in controlling hyperemesis in pregnancy (37). The therapies are as diverse as the providers who recommend them. Acupressure and acupuncture (38,39), gingerroot (40), and hypnosis or hypnotherapy (41) are among modalities
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TABLE 4 (45– 47)
Pharmacologic Regimens for the Treatment of Hyperemesis Gravidarum Parenteral Therapy: Intravenous fluids (D5 & 1/2NS) with additional K⫹ as necessary; total parenteral nutrition with appropriate additives, including K⫹ and multivitamins, particularly thiamin, B6 and B12. Pharmacologic Therapy Drug (Commercial Name)
FDA Risk Category
Dose
Vitamin B6 (pyridoxine) Promethazine (Phenergan) Droperidol (Inapsine) Combination therapy of droperidol and diphenhydramine
A C
30 mg qd 25 mg po/rectal suppositories q4–6h
CM CM
0.625–1.25 mg IV/IM 25 mg in 500 mL NS @ 1 mg (20 mL)/h IV and 50 mg IV q6h (begin before droperidol)
Prochlorperazine (Compazine)
C
Trimethobenzamide (Tigan)
C
5–10 mg PO 3–4⫻/day 2.5–10 mg Not to exceed 40 mg/d Rectal suppository 25 mg bid 250 mg PO tid to qid 200 mg tid to qid or by suppository
Hydroxyzine (Vistrail) (Atarax)
C
25–100 mg q4–6h IM/PO
Metoclopramide (Reglan)
BM
10 mg PO qid Continuous subcutaneous infusion
Ondansetron (Zofran)
BM
4 mg (over 2–5 min) IV/IM 8 mg PO q8h
Methyl Prednisolone (Medrol) Ginger root
B
Multidose regimen (21) 250 mg bid
Major Side Effects/ Contraindications* None known Drowsiness Extrapyramidal signs† Extrapyramidal symptoms Akathisia (restlessness, hyperactivity, anxiety) Dystonia Dizziness Extrapyramidal symptoms Neuroleptic signs Tarditive dyskinesia Extrapyramidal symptoms Hepatotoxicity Blood dyscrasias Possible anomalies with first trimester use: potentiates, narcotics, barbiturates Involuntary motor activity Mental depression Tarditive dyskinesa Acute dystonic reactions Headache Dizziness Musculoskeletal pain Drowsiness Fluid retention Change in carbohydrate tolerance Increased salivation Not to be taken if gallstones present
* A full review of the side effects and contraindications of any agent administered in pregnancy should be undertaken if the provider is not familiar with the pharmacologic agent being dispensed. † Diphenhydramine (Benedryl) is the specific antidote for the extrapyramidal manifestations seen on occasion with the phenothiazines.
discussed in the literature to control or improve hyperemesis. Acupuncture was deemed efficacious in a review of 12 randomized placebo controlled trials as “an effective antiemetic technique” (42). Other investigators (43,44) have found the use of acupressure at the PC-6 point (on the flexor tendon) on the medial aspect of both arms to be beneficial (39). Improvement in nausea, but not vomiting, was demonstrated by these studies (43,44). In a review of the literature addressing several alternative therapies, Murphy (37) noted that some of these studies are flawed in design, selection bias, and face difficulties with comparison to control populations. In her review, it was believed that the best-studied “alternative” remedy was acupressure, which may afford some relief; ginger and pyridoxine were also thought to be beneficial. Care should be exercised in adopting any
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“new” therapy without reasonable demonstration of success based on appropriate investigations. CASE STUDY
M.S. is a 23-year-old gravida 1 para 0 who called her midwife one evening when she was at 8 weeks’ gestational age. Her complaint was nausea and vomiting for the last 24 hours. She was advised to try sips of clear liquids through the evening and to come to the office in the morning if the vomiting persisted. The next morning M.S. came to the office for evaluation. She continued to experience nausea and intermittent emesis. Her weight was 142 pounds, a reduction of 2 pounds from her initial evaluation examination 2 weeks earlier. Her vital signs were normal, but urine specific
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gravity was 1.030 and showed a trace of ketones. The midwife ruled out other potential underlying diseases by a complete history and physical examination and initiated treatment for nausea and vomiting of pregnancy. An IV of D5LR with 50 mg of Phenergan added was administered in the office. After the infusion of 1 L of fluids, M.S. stated that she was much better and was sent home after receiving counseling regarding diet modification and fluid recommendations. She was also given a prescription for Phenergan suppositories (25 mg) to use every 6 hours as needed for nausea. She was advised to take vitamin B6 supplements (50 mg) po twice daily. One week later, M.S. called again to complain of nausea and vomiting. She stated the Phenergan was no longer relieving her symptoms. She had lost an additional 5 pounds, and her urine was very concentrated. A later office check showed 2⫹ ketones. She had tried to use a wet to dry diet, but continued to experience vomiting several times a day. The midwife arranged to have M.S. admitted to the hospital’s antepartum unit for a short stay. At that time, an ultrasonogram was performed, which confirmed an intrauterine pregnancy at 9 weeks’ gestational age. A complete blood count and chemistry panel were obtained, and values were normal except for a potassium level of 3.3 mmol/L (normal range, 3.5–5.3 mmol/L). A urinanalysis showed a high specific gravity and 2⫹ ketones. An IV of D5LR was started along with 0.625 mg of droperidol IV push. One ampule of multivitamin was added to the first liter of IV fluids. The next afternoon, M.S. was tolerating a bland diet, her urine was negative for ketones, and she was discharged with a prescription for Zofran (8 mg) to be taken every 8 hours for nausea. Five days after discharge, at almost 10 weeks’ gestation, M.S. returned to the midwifery service. She had lost an additional 6 pounds, for a total of 13 pounds of weight loss. Urine dipstick indicated 3⫹ ketones. She could not hold down any food and only retained minimal liquids for 2 days. Her potassium was 3.0 mEq/mL. Her hemoglobin was 14.8 g/dL. The midwife recommended hospital admission and contacted the consulting physician for medical evaluation. The medical management included an initial dose of diphenhydramine, 50 mg IV, to be continued every 6 hours; Droperidol, 25 mg in 500mL normal saline, was also started at 1 mg (20mL)/hour IV. Arrangements were made for the placement of a central venous line for total parenteral nutrition. M.S. was allowed nothing by mouth for 2 days, when she requested the initiation of a dry diet. Once established, there was some improvement, and she was discharged to home care with the central line in place. Both the obstetric consultant and the midwife saw her over the next 3 weeks by which time she had resumed a nearly normal diet. After 1 week without nausea or vomiting, the central line was removed, and the manage-
ment of her care was resumed fully by the midwife. The pregnancy progressed to a term delivery without complications. In summary, despite the homeopathic and pharmacologic regimens advocated to date, no single therapeutic approach has consistently proven efficacious in the treatment of HG. The midwife and medical consultant must remain clinically diligent in their evaluation, active in their therapeutic collaboration, and mutually supportive during the patient’s time in recovery. Only by such cooperative use of respective expertise can optimal patient care be rendered and a successful outcome achieved. CONCLUSION
HG is the extreme state of the common complaint of nausea and vomiting in pregnancy. Recognition of its onset and prompt intervention requires midwifery care and support. Prompt use of midwifery and medical resources will minimize long-term care and lead to restitution of normal function and life activity for the afflicted gravida. Dynamic collaborative activity on the part of the midwife and physician will afford the patient who has hyperemesis the optimum of diagnostic and therapeutic assistance. REFERENCES 1. Signorello LB, Harlow BL, Wang S, Erick MA. Saturated fat intake and the risk of severe hyperemesis gravidarum. Epidemiology 1998;9: 636 – 40. 2. Vellacott ID, Cooke EJ, James CE. Nausea and vomiting in early pregnancy. Int J Obstet Gynecol 1988;27:57– 62. 3. Gadsby R, Barnie-Adshead AM, Jagger C. A prospective study of nausea and vomiting during pregnancy. Br J Gen Pract 1993;43:245– 8. 4. Scott LD, Kozinetz C, Gonik B. Gastrointestinal function in pregnancy [abstract]. Gastroenterology 1986;90:1624. 5. Abell TL, Riely CA. Hyperemesis gravidarum. Gastroenterol Clin North Am 1992;21:835– 49. 6. Klebanoff MA, Koslowe PA, Kaslow R, Rhoads GG. Epidemiology of vomiting in early pregnancy. Obstet Gynecol 1985;66:612– 6. 7. Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol 1998; 41:597– 605. 8. Wald NJ, Cuckle HS. Biochemical screening. In: Brock DJH, Rodek CH, Ferguson-Smith MA, eds. Prenatal diagnosis and screening. Edinburgh: Churchill Livingstone, 1992. 9. Deuchar N. Nausea and vomiting in pregnancy: a review of the problem with particular regard to psychological and social aspects. Br J Obstet Gynaecol 1995;102:6 –10. 10. Frigo P, Lang C, Reisenberger K, Kolbl H, Hirschl AM. Hyperemesis gravidarum associated with Helicobacter pylori seropositivity. Obstet Gynecol 1998;91:615–7. 11. Goodwin TM, Hershman JM, Cole L. Increased concentration of the free -subunit of human chorionic gonadotropin in hyperemesis gravidarum. Acta Obstet Gynecol Scand 1994;73:770 –2. 12. Goodwin TM, Mestman J. Transient hyperthyroidism of hyperemesis gravidarum. Cont Ob-Gyn 1996;41(6):65–78. 13. Price A, Davies R, Heller SR, Milford-Ward A, Weetman AP. Asian
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