Indomethacin therapy in hydramnios.S Abhyankar, VS Salvi
Department of Obstetrics and Gynaecology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai - 400 012, India., India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 11298464
Source of Support: None, Conflict of Interest: None
AIM: The use of indomethacin in treatment of hydramnios was evaluated. SUBJECTS & METHODS: Twelve patients with symptomatic hydramnios were treated with indomethacin (2.2- 3.0 mg/kg body weight/day). RESULTS: The treatment was started at a gestational age of 31.17-/+7.94 weeks and continued for 3.74-/+2.3 weeks. Eleven patients responded to the therapy both subjectively and objectively and pregnancies were prolonged by 4.6-/+3.1 weeks (range 0.1-10 weeks). Five women had term deliveries. Six patients had a favourable perinatal outcome. Four patients who had a known congenital anomaly in the foetus, delivered stillborn babies or had an early neonatal death. One patient who did not follow up after commencing therapy delivered a full-term stillbirth. One patient delivered within 1 day of starting therapy. Indomethacin therapy caused no maternal complications. CONCLUSION: Indomethacin was effective in the management of hydramnios and preventing it's complications.
Keywords: Adult, Anti-Inflammatory Agents, Non-Steroidal, administration &dosage,Drug Administration Schedule, Female, Follow-Up Studies, Gestational Age, Human, Indomethacin, administration &dosage,Polyhydramnios, drug therapy,ultrasonography,Pregnancy, Pregnancy Outcome, Severity of Illness Index, Treatment Outcome, Ultrasonography, Prenatal, methods,
Polyhydramnios has been defined as an amniotic fluid volume greater than 2000 ml. Though, the incidence is less than 1%, it is still a source of worry for obstetricians as it can jeopardise both maternal and foetal outcome.,, The maternal hazards include respiratory compromise, antepartum haemorrhage, abnormal presentations, uterine dysfunction, postpartum haemorrhage and increased operative intervention. The perinatal outcome is compromised due to prematurity, placental abruption and umbilical cord prolapse. Moreover, the causes of polyhydramnios such as diabetes mellitus, congenital malformations and twins are also associated with an adverse perinatal outcome.
No active management may be required in patients with asymptomatic hydramnios. For patients developing evidence of respiratory embarrassment, excessive uterine activity or premature opening of os one of the therapeutic options is decompression by amniocentesis. However it has a risk of preterm labour and infections. The medical management of hydramnios utilising indomethacin was first reported by Cabrol. Though the use of indomethacin is described in standard literature, there are very few cases of symptomatic hydramnios requiring therapy. Worldwide only 56 cases have been reported.,,,,,,,,,,,,,, We report 12 cases of symptomatic hydramnios treated with indomethacin.
Twelve cases of symptomatic hydramnios requiring treatment at the KEM Hospital, Mumbai, over a period of 10 years (1990-1999) are being reported. Hydramnios was diagnosed clinically and confirmed by ultrasound. Clinically, the patients had a fundal height greater than the period of amenorrhoea , foetal parts were not easily palpable, foetal heart sounds were heard as if coming from a distance and a fluid thrill was present. At ultrasound examination the largest pocket of amniotic fluid was measured. Hydramnios was graded as mild, moderate and severe if the largest vertical pocket of liquor measured 8 to 11cm, 12 to 15 cm and greater than 16 cm respectively.
The patients received indomethacin only if they had symptoms due to hydramnios such as respiratory embarrassment, premature opening of os or presence of uterine activity. Since mild hydramnios is relatively uncomplicated, indomethacin was utilised only in moderate and severe hydramnios. The only exception was a patient with mild hydramnios in both sacs of a twin gestation. Patients were evaluated for determining the cause of hydramnios such as maternal diabetes, rhesus incompatibility, or a congenital anomaly in the foetus.
Indomethacin was given in a dose of 2.2-3 mg/kg/day (75 mg twice daily). The changes in the following parameters were evaluated to determine the effect of indomethacin therapy a) maternal symptoms and uterine contractions; b) weekly measurement of fundal height and abdominal girth at the level of the umbilicus and serial ultrasound (to monitor foetal growth and amniotic fluid); and c) prolongation of pregnancy.
The results are depicted in [Table - 1]. All the patients except one had either moderate or severe hydramnios. All the patients complained of abdominal discomfort and respiratory embarrassment. Three of the cases already had premature opening of os. Patient No. 6 had a history of being tapped in the current pregnancy and 500 ml of amniotic fluid had been drained. The patients had a gestational age of 31.17?7.95 weeks (range 28-37 weeks). The fundal height was 37.67? 9.96 cm (range 32-48 cm). Hydramnios was idiopathic in 6 patients, 2 patients had a twin gestation and 4 foetuses were anomalous. Two patients had concomitant gestational diabetes. The therapy was given for a period of 3.74?2.32 weeks (range 0.14-8 weeks). All the patients except one (No 9) were relieved of their abdominal discomfort and respiratory embarrassment. Patient No 9 went into preterm labour, within a day of starting indomethacin and the baby expired due to extreme prematurity. In 10 patients, the hydramnios decreased both clinically and on ultrasound while in patient no 1 the fundal height remained static. Five patients went to term while the remaining 6 patients could be carried forward to 34 to 36 weeks. Delivery was postponed by 4.6?3.1 weeks (range 0.1-10 weeks). Six cases had a successful perinatal outcome. Case 7 did not follow up after initiating indomethacin therapy and came directly in labour with an intrauterine foetal death. All the four babies with congenital anomalies did not survive. There were no maternal complications except in case four who had sudden intrapartum bleeding at full dilatation.
Indomethacin is an anti-prostaglandin, which acts by reversible inhibition of the enzyme cyclo-oxygenase. Foetal urination and foetal lung fluid are major sources of amniotic fluid production and are balanced by fluid removal through foetal swallowing and intra-membranous absorption across the foetal surface of the placenta. Indomethacin acts by decreasing the production of amniotic fluid by reducing the urine output and also by increasing fluid reabsorption by the lungs secondary to foetal breathing and increased fluid movement across foetal membranes. Indomethacin is thought to act by impairing the normal prostaglandin mediated response of the renal vasculature.
A total of 56 patients have been reported in English literature in whom indomethacin was used in treatment of polyhydramnios. As in the current study, all the investigators enrolled patients only if maternal compromise in the form of cardio-respiratory embarrassment, abdominal pain or preterm labour were present. Although diagnostic criteria for hydramnios varied with each investigator, ultrasound was routinely used in all the patients.
In the 56 reported cases, 19 mothers had diabetes mellitus, 16 cases were idiopathic and 15 had a multiple gestation. There were two cases of foetal gastro-intestinal anomalies and one case each of foetal diabetes insipidus and neuro-muscular disorder. One mother was on haemodialysis while one had a chorio-angioma of the placenta.
In the current study, indomethacin was used in a dose of 2.2 to 3 mg/kg body weight, which is the same as that used by Cabrol. The lowest dose used in other studies was 25 mg 12 hourly, and at times the drug has also been administered per rectally in a few patients.
In the current study, delivery was postponed by 4.6?3.1 weeks and 50% of the pregnancies had a successful outcome.
In previous studies utilising indomethacin, maternal side effects were limited to nausea or epigastric discomfort. Rectal dosage produced rectal irritation. Some studies have shown maternal renal insufficiency after prolonged treatment. In the current study, there were no gastro-intestinal side effects. There were no maternal complications attributable to indomethacin.
Amniocentesis has also been described as therapy for hydramnios but it is an invasive procedure and multiple taps may be required. Complications of therapeutic amniocentesis include preterm labour, abruptio placenta, chorioamnio-nitis. In a study conducted by Elliott et al, of the 94 patients who had undergone therapeutic amniocentesis, 3 patients developed maternal complications like premature rupture of membranes, chorioamnionitis and antepartum haemorrhage. The ability of therapeutic amniocentesis to prolong pregnancy has only been addressed by Radestad. They utilised this procedure in acute polyhydramnios in twin pregnancy. Pregnancy was prolonged by 2 weeks in the group managed by amniocentesis as compared to 1 week in the conservatively managed group. In the current study, pregnancy was prolonged by 4.6?3.1 weeks in patients treated with indomethacin.
The use of indomethacin has raised concerns about premature closure of the ductus arteriosus. Though Moise and colleagues in 1988 reported that 50% of 14 foetuses whose mothers received indomethacin had ductal constriction detected by Doppler, persistent constriction was not demonstrated in the studies described earlier nor has it been described in the studies in which indomethacin was given for tocolysis. In the study by Dudley indomethacin was given up to 35 weeks and no foetal complication was noticed. In Vermillion’s study too, a dramatic reversal of ductal constriction was noted after stopping indomethacin and no significant adverse foetal outcome was attributed to indomethacin therapy. Though, all the cases with morphologically normal foetuses, in whom therapy was antenatally monitored, delivered healthy normal neonates, we suggest that indomethacin be used only in cases of symptomatic hydramnios where maternal well-being overrides concerns of foetal safety.
In conclusion, indomethacin can be used effectively in the therapeutic management of hydramnios in pregnancy.
[Table - 1]