Department of Obstetrics and Gynaecology, Iizuka Hospital, Fukuoka, Japan
Hyperemesis gravidarum is a clinical condition in which pernicious vomiting of pregnancy, which is manifested chiefly by gastrointestinal symptoms, leads to deterioration and impaired intake of meals, nutritional and metabolic disturbances, and a status requiring treatment.
The current therapeutic modality for hyperemesis gravidarum is palliative treatment which is based on fluid therapy. There are many patients who fail to be improved by fluid therapy alone. Since hyperemesis gravidarum develops in coincidence with the phase of organogenesis in the early stages of pregnancy, antiemetics are generally not administered. Chinese herbal medicines, which are considered effective and safe for morning sickness and hyperemesis gravidarum in East Asia, present some disadvantages when ingested orally, e.g., induction of nausea because of their characteristic odour. Because of the above reason, we formulated and used suppositories of Chinese herbal medicine extracts. The chief symptoms of hyperemesis gravidarum are subjective, making it difficult to compare the symptoms and evaluate efficacy of treatment. In the present clinical trial, therefore, we categorised symptoms by severity and evaluated therapeutic efficacy according to a questionnaire-based survey using the Index for Nausea and Vomiting of Pregnancy (INVP), Table 1.
The present clinical trial was conducted from April, 1997 to August, 1998 for pregnant women in whom ultrasonography confirmed heart beats of the foetus in the uterine cavity, who showed nausea or vomiting, and who gave consent to the use of Chinese medicine extract suppositories.
Preparation of Chinese Herbal Medicine Suppositories
Hard fat (1.5 g, Witepsol S55) was melted by warming and used as the base. Subsequently, 1.25 g of Chinese herbal medicine extract granules were mixed with the base, and the mixture was stirred well. The mixture was then poured into a suppository mould and cooled to obtain solid suppositories.
Two suppositories were equivalent to one dose of oral extract. Although these Chinese herbal medicine suppositories differ little from the commercial ones in terms of both shape and size, their colour is dark brown. The suppositories were stored in a cool place.
The following Chinese herbal medicine extracts were used: TSUMURA Hange-koboku-to Extract Granules for Ethical Use (TJ-16) as Suppository HKT; and TSUMURA Bukuryon-in-go-hange-koboku-to Extract Granules for Ethical Use (TJ-116) as Suppository BIH.
Usage of Chinese Herbal Medicine Suppositories
The Chinese herbal medicine suppositories were used in combination with fluid therapy. H2-receptor antagonists were also administered intravenously for reflux oesophagitis and gastritis. One or two suppositories were inserted into the anus 30 minutes before each meal and at bedtime.
Suppository HKT was used as the drug of first choice for patients who had nausea or vomiting. Suppository BIH was used for patients who showed symptoms of reflux oesophagitis or gastritis.
Items of Examination
To evaluate the efficacy of the Chinese herbal medicine suppositories, a questionnaire-based survey, on the basis of the INVP, was conducted after the termination of the present clinical trial. The questionnaire required the selection of the options in Table 1 in terms of symptoms found before and after treatment.
The INVP values represented the total score of six items in terms of the symptoms that were found before and after treatment. Symptoms were categorised as follows: "less than mild", when INVP values were 2 points or lower; "mild", when the INVP values were 3 to 6 points; "moderate", when INVP values were 7 to 12 points; and "severe", when the INVP values were 13 to 18 points.
Categories for the Efficacy of the Treatment
The efficacy of the treatment was categorised as follows: "excellent effect", when the INVP values, being 3 points or higher before treatment, decreased to 2 points or lower after treatment; "good effect", when the INVP values, being 3 points or higher before treatment, decreased to 2 points or higher after treatment; and "poor effect", when the INVP values remained unchanged or increased after treatment.
There were three patient groups: Group I of outpatients; Group II of patients who were hospitalised due to hyperemesis gravidarum (showing no complications other than gastritis and reflux oesophagitis); and Group III of patients who were hospitalised due to threatened abortion (showing symptoms of hyperemesis during hospitalisation).
Each group was further divided into the subgroups of Suppository HKT and Suppository BIH. The patients, for whom the suppository was changed from HKT to BIH, were considered as patients who used suppository BIH.
The Wilcoxon test was used to evaluate the efficacy of the treatment, with a significant difference at p = 0.05.
The number of patients in whom the suppositories were used were as follows: 21 for HKT and two for BIH in Group I; 13 for HKT and 13 for BIH in Group II; and five for HKT and one for BIH in Group III. Of these, the number of patients who replied to the questionnaire were as follows: 16 for HKT and one for BIH in Group I; 10 for HKT and 13 for BIH in Group II; and five for HKT and one for BIH in Group III.
The INVP values before and after treatment are shown in Figure 1. The means of the INVP values in Group I were 9.4 ± 3.0 points and 4.1 ± 2.3 points; in Group II they were 13.1 ± 4.0 points and 4.3 ± 4.0 points; and in Group III they were 8.7 ± 3.4 points and 4.3 ± 1.5 points before and after treatment. Therefore, a significant difference was found in all groups.
Furthermore, the means of the INVP values by drug were as follows: for HKT, 10.0 ± 4.0 points before treatment and 4.0 ± 2.5 points after treatment; and for BIH, 12.9 ± 4.0 points before treatment and 4.0 ± 2.8 points after treatment. Therefore, a significant difference was found in the total scores which were determined before and after treatment.
Six patients had side effects using the suppositories; all side effects were watery diarrhoea. Two of these patients discontinued using the suppository.
It is difficult to evaluate hyperemesis gravidarum objectively, because of the fact that it mainly consists of subjective symptoms. Furthermore, the number of classes of the complaints considered to be symptoms of hyperemesis gravidarum is as numerous as 20. Based on the above background, the Emesis Index (EI) has been created, modified and used. The EI originally created chiefly consisted of three symptoms of high incidence and intense severity, i.e., nausea, vomiting, and appetite. The INVP, modified to include the symptoms of salivation and dryness of mouth and acetone in the urine, was used in the present clinical trial. The INVP is thought to be more useful than the EI for evaluating hyperemesis gravidarum.
Fluid therapy was combined in treating many cases. Suppositories alone were used in the majority of outpatients and in the inpatients who detested the odour of the fluid. These patients showed no particular problems, and the improving process of symptoms did not differ from the patients in whom fluid therapy was combined. In the patients in whom fluid therapy was used alone and in combination with suppositories, symptoms improved earlier at the time of combined therapy than at the time of fluid therapy alone.
Herbal remedies are recommended commonly for nausea and vomiting of pregnancy.1 Chinese herbal medicine suppositories appear to be a reasonable therapeutic alternative for hyperemesis gravidarum. A randomised trial is needed to confirm the efficacy of Chinese herbal medicine suppositories for hyperemesis gravidarum.
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