To compare the efficacy of Drotaverine hydrochloride and Valethamate bromide in shortening of the first stage of labour

Background: To compare the efficacy of Drotaverine Hydrochloride and Valethamate Bromide in shortening of the first stage of Labor. Drotaverine is more effective in regards of shorten the 1st stage of labor, rate of cervical dilatation with less side effects in compare to Valethamate Bromide.   Methods: Two Hundred demographically similes woman with full term pregnancy in active labour were included in the study and divided into two groups viz.  First Group: 100 women were given injection Drotaverine Hydrochloride (Drotin) 40 mg intramuscularly at 3-4 cm dilation at two hour interval.  Second Group: 100 women were given injection Valethamate Bromide Intramuscularly at 3-4 cm dilation at one hour interval.  Maximum three injections were given in both the groups. Comparative analysis was carried out as regards to duration of various stages of labor, rate of cervical dilatation, mode of delivery, side effects and feto-maternal outcome.   Results: In Group-I Average duration of active phase of first stage of labor was 149.78 minutes.   In Primigravida it was 170.22 minutes and 129.35 minutes in Multigravida.  In Group II Average duration of active phase of first stage of labor was 294.62 minutes.  In Primigravida it was 321.71 minutes and 267.54 minutes in Multigravida.  Average rate of cervical dilatation in Group-I was 2.81cm/hour. In Primigravida it was 2.50 cm/hour while in Multi gravid it was 3.33cm/hour.  In Group-II average rate was 1.42 cm/hour, in Primigravida it was 1.30 cm/hour and in Multigravida1.57 cm/hour.   Conclusions: Drotaverine significantly shorten the duration of first stage of labor and found to be safe with no adverse effect on the mother and fetus.

section_content: Drotaverine Hydrochloride: It is a phosphodiasterase 4 enzyme inhibitor a new addition to cervical dilator. It was initially used in Europe for spasmodic condition like renal, ureteric and biliary colic and in dysmenorrhea. 3, 4 ts use for cervical dilatation was first studied by Chinoin in 1963 in Hungary. 5 otaverine is Benzyle Iso Quinoline derivative. It causes smooth muscle relaxation by increasing cellular level of cyclic adenosine monophosphate (CAMP), secondary to inhibition of phosphodiesterase four enzyme. The Pharmacological dose of Drotaverine unable to inhibit labour contraction but relaxes only the smooth muscle tone of lower uterine segment and cervix 4, that's why the active labour pains are not inhibited, It is safe to mother and foetus with no drug interaction. 5 lethamate Bromide (Epidosin): It is an ester of quatery ammonium compound; it is an anticholinergic, antispasmodic, musculotropic and neurotropic agent having peripheral action similar to atropine. It is a potent and rapidly acting drug which helps in cervical dilatation. It has side effect like dryness of mouth, flushing of face, nausea, Vomiting, nervousness, giddiness, hypotension due to its effect in smooth muscle of vessel wall. 5, 6

section_content: A prospective randomized, controlled clinical trial was conducted in the department of obstetrics and Gynecology at Chhattisgarh Institute of Medical Sciences Bilaspur during the period of December 2013 to December 2014. Detail history of cases has been taken regarding age, occupation and socio economic status. Their presenting complaints were recorded with special attention to Period of amenorrhea, duration since onset of labour pain, leaking per vaginum and other complain. If any obstetric history was elicited regarding outcome of previous pregnancies, any history of prolong labour, retained placenta, abortion, preterm labor or still birth. Past history regarding any major illness or systemic disease was also taken. Detail Clinical and physical examination have been performed. Per abdomen examination with special attention for height of the uterus, presentation and frequency of contractions was noted. Foetal well-being was monitored by noting the heart rate, rhythm and regularity of foetal heart sound. By per vaginum examination cervical dilatation, effacement, consistency and station of presenting part were noted. Pelvic examination was performed to exclude any pelvic contraction or cephalopelvic disproportion. 

Routine investigations advised including Hb, BT,CT, Blood grouping,Blood sugar, Sickling, VDRL, HIV, HbS-Ag and Urine for routine and microscopic examination, Following inclusion and exclusion criteria were considered for selection of the uncomplicated patients: Inclusion criteria: In Group I (n=100) cases received Intramuscular (IM) Drotaverine 40 mg in supine position. Injection was repeated after 2 hours as per requirement (Cervical dilatation <7 cm) to maximum of three Injections. 

In Group II (n=100) cases received IM injection of Valethamate Bromide 8 mg at hourly interval to maximum of three. 

Continues monitoring of maternal and fetal condition was observed. Any abnormality if detected was managed accordingly. Evaluation of uterine activity was observed 1/2 hourly to assess the frequency and duration of contraction. 

Any relation with drug administration to uterine contraction was especially noted. 

Per vaginum examination was performed at the beginning of labour, at the time of administration of Drotaverine or Valethamate Bromide hourly, during labor and at further doses of drug, if required. 

All events of labor were graphically recorded in the form of Partograph. If labor did not end within 12 hours spontaneously, it was considered as failure of acceleration of labor and other methods of termination of pregnancy were looked for. Other outcome variables like injection delivery interval, total doses of drug required, route of delivery, incidence of operative interference, duration of first, second and third stages of labor, amount of blood loss, complications of the third stage like cervical tear, retained placenta, post-partum hemorrhage etc. were noted. Foetal outcome in terms of live or stillbirth, weight, Apgar scoring at 1 min and 5 min were recorded. Both mother and the baby were followed up for at least 48 hours.
section_name: METHODS

section_content: In the present study there was no significant difference in the demographic distribution, socioeconomic state, age, gravidity and registration of case in both the groups (Table 1 ). 3 ). Side effects like tachycardia were 4% in Group-I and 31% in Group-II. Dryness of mouth, flushing of face was more observed in Group-II (Table 6 ). 

There is no significant difference of mode of delivery. No newborn in Group-I has Apgar score less than 8 at birth but in Group-II four newborn had Apgar score less than 8 at birth. 

There was no foetal death in the groups, one case of PPH and one case of cervical tear found in Group-II (Table 7 ).
section_name: RESULTS

section_content: Acceleration of labor is considered to be an important factor in reducing maternal and neonatal morbidity. 1 ince long back Valethamate Bromide is used to relive cervical spasm. 6 newer drug Drotaverine is an iso-quinoline derivative acting by inhibition of phosphodiesterase enzyme type four4. That causes relaxation of smooth muscles. In addition it also has spasmolytic action. 5 our study Drotaverine is used during active dilatory phase of labor and results were compared with IM Valethamate Bromide injection. It was found Intramuscular administration of Drotaverine significantly reduces the duration of cervical dilatation and total delivery time. [3] [4] In present study duration of delivery is significantly shorten in Drotaverine group which is similar to finding of Kaur1 149. 82 ± 63 minutes.
section_name: DISCUSSION

section_content: Valethamate Bromide on cervical dilatation. They found average rate of cervical dilatation in primigravida with Drotaverine was 2. 05cm/hour and with Valethamate Bromide 1. 53 cm/hour. In Multigravida it was 3. 68 cm/hour and 2 cm/hour respectively. They found with Drotaverine the duration of labor was significantly shorten. 2 In our study we have observed almost similar findings. 

Pai et al. ( 2003 ) also found similar effect on cervical dilatation, shortening of labor time in their study. 3 nka, Khosla also found Drotaverine is very effective agent to relive cervical spasm. 7, 8 lay et al., Sharma JB, Nagria found Valethamate Bromide had more anti cholinergic side effects than Drotaverine. The same finding we have observed in our study. 

Drotaverine improves the cervical dilation rate which is supported by various previous studies (Table 8 ). 

In present study cervical dilatation rate was significantly higher and faster in Drotaverine group in comparison to Valethamate Bromide group. ] [10] [11] In present study we also observed the Drotaverine group had identical results. 

Valethamide Bromide is associated with higher incidence of adverse effect in therapeutic dose. 1, 6, 8, 11 Moreover present study also shows significantly higher incidence of minor adverse effect with Valethamate Bromide. Duration of second stage, third stage of labor, mode of delivery, maternal and neonatal outcome were similar in both group. 12
section_name: Mishra SL et al (2002) studied effect of Drotaverine and

section_content: Drotaverine significantly shortens the duration of first stage of labour and does not interfere with uterine contractility. Moreover it found to be safe with no adverse effect on mother and foetus. For this reason it is a better choice than Valethamate Bromide for shortening at the first stage of labour if used after proper selection of cases. Abbreviations: P-Primigravida, M-Multigravida, IDI-Injection Delivery interval, DM-Dryness of Mouth, T-Tachycardia, N-Nausea,V-Vomiting, F-Flushing, P-Palpitation
section_name: CONCLUSIONS

section_name: Funding: No funding sources

section_name: Conflict of interest: None declared Ethical approval: Approved by institutional ethics committee