Home subcutaneous metoclopramide therapy for hyperemesis gravidarum

L. Buttino Jr., MD, C. Gambon, RN, BSN, S. Coleman, MS, RNC
Franciscan Medical Centre, Dayton, Ohio and Matria Healthcare Inc., Marietta, Georgia, U.S.A.

Background

Hyperemesis gravidarum is characterized by intractable nausea and vomiting in pregnancy with concurrent disturbances of nutrition and fluid balances.It is sometimes defined with a loss of > 5% pre-pregnancy weight.1 The pathophysiology is unknown and it remains a problem that is poorly understood and largely ignored in clinical research. It is relatively uncommon, occurring in approximately 1-2% of all pregnancies, but accounting for nearly 5% of all antenatal hospital admissions and 30% of admissions prior to 20 weeks' gestation.2 All obstetricians have been faced with the challenge of effectively treating hyperemesis gravidarum while trying to keep their patients from being admitted to the hospital. There is insufficient data available on effective treatment of nausea and vomiting in pregnancy, much less the extreme condition of hyperemesis gravidarum. Treatment for this disorder may include nutritional counselling, intravenous hydration, total parenteral nutrition, and antiemetic medications. The most commonly prescribed antiemetics are prochlorperazine (Compazine), trimethobenzamide (Tigan), promethazine (Phenergan), chlorpromazine (Thorazine), transdermal scopolamine, and metoclopramide (Reglan). Many of these medications may be given via rectal suppository, thus avoiding the gastrointestinal tract and allowing self-medication. In severe cases subcutaneous (SC), intramuscular (IM), or intravenous (IV) routes may be used.1,3-6 However, there are few reliable recommendations available. Successful subcutaneous metoclopramide therapy has been reported for the treatment of gastroparesis and chemotherapy-induced emesis.7,8 In 1994, home subcutaneous metoclopramide therapy (SMT) was made available for the treatment of hyperemesis gravidarum. The purpose of this study is to report on the effectiveness and cost efficiency of that therapy.

Methods

Data were reviewed from patients who received subcutaneous therapy from January 1, 1994 through December 31, 1995 (Group I) and from January 1, 1997 through December 31, 1997 (Group II). Every effort was made to manage patients with the least complicated or invasive therapies. Simple interventions (diet modifications, over-the-counter medications, etc.) were always attempted first. Only after persistent or recurrent symptoms, in spite of the initial therapies, was SMT initiated by a perinatal nurse at the hospital or in the home. Included during therapy initiation were: thorough education on diet modification, pump operation, infusion site maintenance and rotation, and emergency procedures. The SMT protocol included an initial 10 mg loading dose, administered either IM or IV followed by continuous SC administration via a portable, programmable micro-infusion pump (MiniMed 404SP - MiniMed Technologies, Sylmar, CA). The continuous infusion rate was titrated based on the patient's symptoms. Once the patient reported cessation of symptoms, the infusion rate was held constant. Additional patient instructions included: nothing by mouth (NPO) until symptoms abated, plus activity level, diet advancement and metoclopramide dosage decreased, as tolerated. A total of 301 patients are included in Group I and 853 patients in Group II. Data were collected on patient location at initiation of SMT, need for adjuvant therapy (other antiemetics and IV hydration) pre- and post-SMT, average effective dose, number of dose increases during therapy, side effects and adverse reactions to therapy, and outcome.

Results

During the initial study period 192 (63.9%) patients were started on SMT in the hospital or physician's office, with 109 (36.1%) started at home. However, as SMT became more widely available and utilized, those numbers reversed; during 1997, 311 (36.5%) patients had SMT initiated in the hospital or physician's office and 542 (63.5%) at home. This trend probably represents two factors. Firstly, initial concern about the safety or side effects of this new form or therapy decreased as it was proven safe. Secondly, obstetricians realized that hospitalization was no longer necessary with most symptomatic hyperemesis gravidarum patients and that many patients who historically had been admitted for this diagnosis could now be effectively managed at home with SMT.

A very significant difference was found in the need for either antiemetics or IV hydration pre-SMT versus post-SMT (Table 1). Information on IV hydration was not available for Group I, but only six patients in whom hyperemesis was resolved required additional antiemetics after discontinuation of SMT. For Group II the need for both antiemetics and IV hydration dropped substantially after successful SMT.

Table 1

 

Forty-eight and one-half percent (48.5%) of Group I and 49% of Group II were managed with the initial baseline dose or one increase in baseline dosage during therapy. The average effective maintenance dose was low for both groups (Table 2).

Table 2

 

In Group I a total of 164 (54.5%) patients experienced side effects. Most patients experienced more than one side effect, but the vast majority were reportedly mild and did not require discontinuation of therapy. One hundred and thirty-seven (45.5%) patients experienced no side effects at all. In Group II, 427 (49.9%) patients experienced some side effects. Fewer patients in Group II experienced multiple side effects and again most side effects were reportedly mild. A total of 429 (50.1%) patients in Group II experienced no side effects. Only 11 (3.6%) patients in Group I and 105 (12.3%) patients in Group II experienced extra-pyramidal symptoms (EPS). Although there is a slightly higher incidence of EPS for Group II compared to Group I, it is consistent with the reported incidence (10-13%) of this type of adverse reaction associated with the administration of metoclopramide (Table 3).7,8

Table 3

 

Outcome in these patients was very encouraging. In Group I, 195 (54.7%) patients had resolution of their hyperemesis gravidarum. This improved to 640 (75.0%) patients in Group II. These are very positive numbers for a single form of therapy. Historically, this success rate has been achieved with hyperemesis gravidarum patients largely through the use of multiple therapies/agents in sequence or in combination, normally requiring prolonged or recurrent hospitalization. Worsening of the symptoms of hyperemesis gravidarum in spite of therapy is common; however, it occurred in only 43 (14.3%) patients in Group I and 59 (6.9%) patients in Group II. This is positive data to recommend home subcutaneous metoclopramide therapy. The percentage of patients who discontinued therapy due to side effects remained low and fairly constant at 10.6% and 12.7% in Groups I and II respectively (Table 4).

Table 4

 

According to the Normative Health Care Measures the average daily charge for patients treated for ICD-9-CM 643.13, "Hyperemesis with metabolic disturbance-Antepartum", in the hospital is US$976.00. When compared to that of home subcutaneous metoclopramide therapy of US$265.00/day, there is clear economic advantage to utilizing this new therapy.

Finally, the added benefit for these stressed and disheartened patients, of being treated in their own homes and familiar surroundings with their families and support networks, cannot be overestimated.

Conclusion

Hyperemesis gravidarum is a complication that occurs in a small percentage of pregnancies but accounts for approximately 78,000 patients annually. Historically, this condition has had high costs in loss of productivity, physical and emotional sequellae, and prolonged and/or recurrent hospital admissions. The use of home subcutaneous metoclopramide therapy appears to be effective, safe, economical, and a way to treat these woeful patients in a familiar, secure, and emotionally supportive environment, which may hasten recovery.

References:

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  3. Leathem AM. Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy. Clin Pharm 1986;5:660-8.
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  7. McCallum RW, Valenzuela G, Polepalle S, Spyker D. Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. J Pharmacol Exp Ther 1991;258:136-42.
  8. Bruera E, Michaud M, Partington J, Brenneis C, Paterson AH, MacDonald RN. Continuous subcutaneous (CS) infusion of metoclopramide (MCP) using a plastic disposable infusor for the treatment of chemotherapy-induced emesis. J Pain Symptom Manage 1988;3:105-7.

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