Gen. Health Med. Sci., Vol(2), No (1), February, 2015. pp.

1-4

TI Journals

ISSN:

General Health and Medical Sciences

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Different Modalities in First Stage Enhancement of Labor

Mahmoud Edessy
Professor and head of Obstet. & Gynecol. Depart. Faculty of Medicine- Al-Azhar University Assiut, Egypt.

Abd El-Aziz G. EL-Darwish

Professor of Obstet. & Gynecol. Depart. Faculty of Medicine- Al-Azhar University Assiut, Egypt.

Ahmed A.M. Nasr

Assistant Professor of Obstet. & Gynecol. Depart. Faculty of Medicine- Al-Azhar University Assiut, Egypt.

Abd El-Naser Abd El-Gaber Ali

Assistant Professor of Obstet. & Gynecol. Depart. Faculty of Medicine- Al-Azhar University Assiut, Egypt.

Hosam El-Katatny
Assistant Professor of Obstet. & Gynecol. Depart. Faculty of Medicine- Al-Azhar University Assiut, Egypt.

M. Tammam
MBBCH
*Corresponding author: aam_nasr@yahoo.com

Keywords

Abstract

First stage of labor

Drotaverine
Hyoscine N-Butylbromide
Metoclopramide

BACKGROUND: Prolonged labor is one of the most important risk factors for perinatal compromise and, if caused
by obstructed labor, it carries the risk of uterine rupture, postpartum hemorrhage [PPH], puerperal sepsis, and maternal
death.
TYPE OF STUDY: A double-blind, randomized, controlled clinical trial.
OBJECTIVE: This study aimed to find out the effect of Drotaverine, Hyoscine-N-Butylbromide and Metoclopramide
on enhancement of first stage of labor.
SETTING: Obstetrics and Gynecology Departments of Al-Azhar university [Assiut] and Sohag general hospitals.
DURATION: From October 2012 to July 2013.
PATIENTS&METHDS: 200 full term primigravidae in labor [3-4cm dilation of internal os with regular progressive
uterine contractions 3-4 per 10 minutes, each lasting for at least 40 seconds] were recruited to this study. Patients were
divided into four groups [50 patients for each group]: Group I: Received [40mg] drotaverine hydrochloride slowly
intravenously. Group II: Received [20mg] hyoscine-n-butylbromide slowly intravenously. Group III: Received [20mg]
metoclopramide slowly intravenously. Group IV [control]: Received Sterile water for injection [placebo].
RESULTS: There was no statistically significant difference among studied groups as regard to maternal age, BMI,
GA, cervical dilatation and cervical effacement at start of study with p value > 0.05. There were highly statistically
significant differences among groups as regard to durations of 1st stage of labor, cervical dilatation after start of study
and amount of oxytocin augmentation used with p value <0.001. There were moderately significances as regard to
neonatal outcome [APGAR score and NICU admission] with p value <0.01 but there was no statistically significant
difference among studied groups as regard to, duration of 2nd stage of labor, mode of delivery and birth weight with p
value > 0.05. There were mildly statistically significant differences among groups in degree of labor pain and maternal
adverse effects of drugs used in this study with p value < 0.05.
CONCLUSION: All drugs used in this study had significant effects on shortening of 1st stage of labor with better
neonatal outcome but Drotaverine hydrochloride had the upper hand as it was more effective beside it had the
strongest labor pain relieve and lesser maternal adverse effects. RECOMMENDATIONS: We recommend using
Drotaverine hydrochloride routinely in enhancing first stage of labor as it cheap, effective with mild significant
maternal adverse effects. More randomized trials on a larger scale are needed to evaluate the utility and safety of these
drugs in labor.

1.

Introduction

Labor is a natural physiological process characterized by progressive increase in frequency, intensity and duration of uterine contractions,
effacement and dilatation of cervix with descent of the fetus through the birth canal [1]. Prolonged labor is one of the most important risk factors
for perinatal compromise and, if caused by obstructed labor, it carries the risk of uterine rupture, postpartum hemorrhage [PPH], puerperal
sepsis, and maternal death [2]. The two major factors that determine duration of labor are uterine contractility and rate of cervical dilation. In
addition to mechanical factors such as sweeping of membranes, cervical stretching [3] and amniotomy [4] various pharmacological agents have
been found to facilitate cervical dilation. The role of oxytocin and prostaglandins has been established worldwide in augmentation of labor [5]
and the cervical application of hyaluronidase has also been used with some success [6].The cervix is made up of only 10 to 15 percent smooth
muscle with the remaining tissue comprised primarily of extracellular connective tissue. Constituents of the latter include type I, III, and IV
collagen, glycosaminoglycans, proteoglycans, and elastin [7]. Cervical softening results from increased vascularity, stromal hypertrophy,
glandular hypertrophy and hyperplasia, and compositional or structural changes of the extracellular matrix [8]. Drotaverine is highly effective in
reducing the duration of active phase of labor by hastening cervical dilatation, more effective when given in more dilated cervix than with less
dilatation and more effective in multigravida than in primigravida. There was no interference with uterine contractility and no increase in
operative delivery. It reduces the incidence of traumatic postpartum hemorrhage by reducing the incidence of cervical tear. It is a safe drug for
the mother as well as for the baby [9]. Only one study was found which looked at hyoscine-n-butylbrmide primarily as an analgesic for the pain
associated with labor. The study was shown that intravenous Hyoscine-N-butylbromide smoothens the passage of labor effects by affording pain
relive of up to 36% and also shortening the duration of active phase without any fetal or maternal complications [10].
Aim of the Work: This study aimed to find out the effect of Drotaverine, Hyoscine-N-Butylbromide and Metoclopramide on enhancement of
first stage of labor.

Mahmoud Edessy, Abd El-Aziz G. EL-Darwish, Ahemed A. M. Nasr *, Abd El-Naser Abd El-Gaber Ali, Hosam El-Katatny , M. Tammam

General Health and Medical Sciences Vol(2), No (1), February, 2015.

2.

Patients and methods

The study was designed as a double-blind, randomized, controlled, clinical trial comparing four groups of women [50 patients for each]; Group I
[Received 40mg of Drotaverine hydrochloride slowly intravenously]. Group II [Received 20mg of Hyoscine-n-butylbromide slowly
intravenously]. Group III [Received 20mg of Metoclopramide slowly intravenously. Group IV [control]: Enrolment for this study commenced in
October 2012 and was completed in July 2013. Women were recruited from the antenatal clinics of our hospitals and full informed consent was
obtained in the antenatal clinic during the patients routine visits. Adequate Opportunity was provided at that time for the women to voice any
questions or concerns regarding the study. Women included in the study were all 20 years or older, were at term, and had no chronic or
pregnancy-induced illnesses. No woman had any contraindication to vaginal delivery, and all women were in established, spontaneous labor.
Established labor was defined as the presence of regular uterine contractions associated with progressive cervical effacement and dilatation. The
syringes containing the drugs and placebo were prepared by the principal investigator, under aseptic conditions and on a rolling basis [i.e. fresh
batches were prepared as additional participants were enrolled]. Each syringe contained either 1 ml of, drotaverine hydrochloride [40mg],
hyoscine butylbromide [20 mg], metoclopramide [20mg] or 1 ml of normal saline; all liquids are colorless, so the syringes containing the drugs
were indistinguishable from those containing placebo. A computer program was used to generate a random sequence of numbers. Sequentially
numbered, sterile syringes were then prepared using the random numbers to determine their content: drugs or placebo. Only the principal
investigator knew the correlation between the labels of the syringes and their contents, and this was only showed after the study was completed.
Participants received drugs as a single dose, given intravenously, when they were assessed as being in labor, with cervical dilatation of 45 cm,
as confirmed and documented by residents in the Obstetrics and Gynaecology departments. The woman and the caregivers were blinded as to
whether the active drug or placebo was being administered. The progress of the participants was closely documented, with the conduct of labor
for both the drugs and control groups in accordance with our normal labor ward protocol, which is based on the principle of active management.
Thus, routine amniotomy was performed for all women in established labor who were found to have cervical dilatation of 3 cm or more, and
who had not had spontaneous rupture of membranes. Oxytocin augmentation was initiated if the initial progress of labor [as assessed through
partographs] was unsatisfactory. Intervention through instrumentation or caesarean delivery was dictated by the usual obstetric determinants.
Laboring mothers were monitored in bed, and the use of electronic cardiotocography assisted in the monitoring of fetal wellbeing. All data
sheets [containing the raw data obtained during the study] were collected by the principal investigator and kept in a combination locked filing
drawer in his office. At the end of the study, the data were disaggregated by the principal investigator, using the record of randomization
sequences and the label of the syringes to sort the participants and their data into the appropriate groups [drugs or control]. The data were then
analyzed using the Statistical Package for the Social Sciences [SPSS].

3.

Results

Statistical analysis
Data were analyzed by computer using SPSS [Statistical Package for Social Science], version 11. The methods used were:
1. Mean x: To measure the average value of a group of data.
2. Standard deviation SD: To measure the degree of dispersion of data around their mean.
3. Students T test: To test the significant difference between two sample means.
4. Chi-square X test: To test the significant difference between percentage and qualitative data.
5. ANOVA [ANalysis Of VAriance] F test; To compare two means or more than two means. The P value was: Insignificant result was
considered if P > 0.05. Mild significant result was considered if P 0.05. Moderate significant result was considered if p <0.01 - High significant result was considered if P 0.001.
There was no statistically significant difference among studied groups as regard to maternal age, BMI, GA, cervical dilatation and cervical
effacement at start of study with p value > 0.05 [Table 1]. There were highly statistically significant differences among groups as regard to
durations of 1st stage of labor, cervical dilatation after start of study and amount of oxytocin augmentation used with p value <0.001 [Table 2].
There were moderately significances as regard to neonatal outcome [APGAR score and NICU admission] with p value <0.01 [Table 3] but there
was no statistically significant difference among studied groups as regard to mode of delivery, duration of 2nd stage of labor and birth weight
with p value > 0.05 [Figure 1 and Tables 2&3 respectively]. There were mildly statistically significant differences among groups in degree of
labor pain and maternal adverse effects of drugs used in this study with p value < 0.05[Table 2 & Figure 2].
Table 1. Comparison among studied groups in maternal age, BMI, GA cervical dilatation and effacement at start of study
Maternal Age in Years MSD
BMI in kg/m2 MSD
Gestational Age in Weeks MSD
Dilatation at time of injection in cm MSD
Cervical effacement at start of study [NO %]
<50%
> 50%

Group I N=50
22.3 2.04
24.1 0.63
39.1 0.80
4.4 0.67

Group II N=50
22.5 1.91
24.0 0.65
39.0 0.77
4.4 0.64

Group III N=50

22.9 2.10
24.2 0.58
39.2 0.77
4.4 0.70

Group IV N=50
22.3 1.49
24.2 0.60
39.40.60
4.3 0.53

P value
0.339 N.S.
0.425 N.S.
0.092 N.S.
0.452 N.S.

24[48]
26[52]

25[50]
25[50]

24[48]
26[52]

25[50]
25[50]

0.155
N.S.

N.S. =Non significant

Table 2. Comparison among studied groups in cervical effacement, durations of laor [1st and 2nd stages] and in oxytocin augmentation
Rate of cervical dilatation in cm/h MSD
Duration of 1st stage in hours MSD
Duration of 2nd stage in minutes MSD
Oxytocin Augmentation in units MSD
Labor pain [NO %]
Moderate
Severe

Group I N=45
1.9 0.55
2.1 0.55
31.0 7.52
5.2 0.54

Group II N=44
1.8 0.59
2.3 0.62
31.4 7.18
7.3 0.74

Group III N=44

1.9 0.59
2.1 0.59
30.7 7.80
8.2 0.72

Group IV N=42
0.98 0.55
3.1 0.78
33.9 7.4
15.7 0.65

P- value
0.001***
0.001***
>0.05 N.S.
0.001***

35 [77.8]
10[22.2]

30[68.2]
14[31.8]

21[47.7]
23[52.3]

18 [42.8]
24[57.2]

< 0.05*

N.S. = Non significant - * mildly significant - *** highly significant

Different Modalities in First Stage Enhancement of Labor

General Health and Medical Sciences Vol(2), No (1), February, 2015.

Table 3. Neonatal outcome in studied groups

Neonatal Outcome
Birth weight in kg MSD
APGAR score at one minute MSD
APGAR score at five minute MSD
NICU admission NO [%]

Group IV N=50
2.9 0.14
7.2 1.08
9.30.69
1[2]

Group III N=50

3.0 0.18
6.8 1.04
8.4 0.70
4[8]

Group II N=50
3.1 0.19
7.0 1.00
8.1 0.73
2[4]

Group I N=50
3.0 0.16
6.1 1.10
7.3 0.83
8[16]

P value
>0.05 N.S.
0.01**
0.01**
0.01**

N.S. = Non significant - * mild significant - **moderate significant

100%

90%

88%

90%

88%

84%

80%
70%

Normal Delivery

60%

Cesarean Section

50%
40%
30%
20%

10%

12%

12%

GI

G II

G III

16%

10%
0%
G IV

Figure 1. Comparison among studied groups in mode of delivery [p value >0.05]

12%
10%

10%
8%

8%
6%

6%

tachycardia

6%
5%

4%

4%
2%

dry tongue

2%

4%

4%

4%

2%

2% 2% 2%

2%
1%

0%

0%
GI

headache

1%

0%
G II

flushing

0%
G III

G IV

Figure 2. Comparison among studied groups in most common side effects [p value < 0.05].

4.

Discussion

Programmed labor protocol is based on incorporation of labor analgesia, active management of labor, and monitoring events of labor using a
partogram [11]. The process of labor puts great strain on the mother and her fetus. Shortening of labor duration would therefore minimize
maternal and fetal morbidity and mortality [12].In this study there was no statistically significant difference among studied groups as regard to
maternal age, BMI, GA, cervical dilatation and cervical effacement at start of study with p value > 0.05. Drotaverine hydrochloride is an
isoquinolone derivative, which has a powerful spasmolytic action on smooth muscle cells by altering the membrane potential and permeability
[13]. In our study Drotaverine hydrochloride showed a significant effect on shortening duration of 1st stage of labor which agreed with many
previous studies had shown that it shortens the duration of labor by 54 min [13] and 218 min [14]. Singh et al. [15] also demonstrated a mean
reduction of 15% and 19% in the duration of the first and second stages of labor, respectively These results are in sharp contrast to what had
been reported by [16] which showed no significant effect of drotaverine hydrochloride on cervical dilation. Other than the study by Singh et al.
[15] no other studies have demonstrated the effect of drotaverine hydrochloride in acceleration of the second stage of labor. Hyoscine-Nbutylbromide is a muscarinic antagonist that acts as a cervical spasmolytic agent. Our study showed a significant effect of Hyoscine-Nbutylbromide on shortening duration of 1st stage of labor which agreed with what had been reported by Sekhavat et al. [17] who showed the
meanSD of first stage duration was [186.8 125.6 minutes] and Baracho and Kamat [18] who stated that the total duration of labor in
primigravida and multigravida women was significantly reduced by 2 h and 1 h 37 min, respectively. Similar observations were also noted by
Bhattacharya and Joshi [19], who reported a significant reduction in the duration of labor with Buscopan. Sirohiwal et al [20] evaluated the
effect of Buscopan suppositories in the active management of labor and found a significant difference in the duration of labor between the
control and study groups [368.05 133.0 min versus 123.8668.89 min, respectively], but our results against what had been reported by Al

Mahmoud Edessy, Abd El-Aziz G. EL-Darwish, Ahemed A. M. Nasr *, Abd El-Naser Abd El-Gaber Ali, Hosam El-Katatny , M. Tammam

General Health and Medical Sciences Vol(2), No (1), February, 2015.

synapses and antagonizing dopamine. The precise mechanism of action of metoclopramide in the first stage of labor is unclear, but it was
documented that the mechanism of action of metoclopramide partially increase the catecholamine which are involved in the process of labor,
however no evidence base studies proved such action. In our study Metoclopramide had a significant effect on shortening duration of 1st stage of
labor and rate of cervical dilatation which agreed with what had reported by Mohamed, [22]. In our study metoclopramide had the least
shortening effect in comparison to other drugs used in this study. In this study there was no statistically significant difference among studied
groups as regard to rate of cesarean section delivery, duration of 2nd stage of labor and these results agreed with what had reported by Tar et al.
[23]. As regard to severity of labor pain, it was lesser in groups I and II [22.2% & 31.8% respectively] than in groups III and IV [52.3% & 57.2%
respectively] with p value <0.05 which agreed with that reported by Samuel et al. [10], Sirohiwal et al. [20], Roy et al. [9] and Aggarwal et al.
[24]. As regard to adverse effects of drugs used in this study, there was mildly statistically significant difference among groups in adverse effects
of drugs used where flushing and tachycardia were more obvious in group II and extra-pyramidal manifestations were only present in group III
which agreed with that reported by Davenport et al. [25]. In this study there were moderately significances as regard to neonatal outcome,
drotaverine hydrochloride and metoclopramide groups had the best neonatal outcome as regard to high APGAR score and low NICU admission
and that agreed with what had reported by Sharma et al. [26] and Tewari et al. [27].

5.

Conclusion

All drugs used in this study had significant effects on shortening of 1st stage of labor with better neonatal outcome but Drotaverine
hydrochloride had the upper hand as it was more effective beside it had the strongest labor pain relieve and lesser maternal adverse effects.

6.

Recommendations

We recommend using Drotaverine hydrochloride routinely in enhancing first stage of labor as it cheap, effective with mild significant maternal
adverse effects. More randomized trials on a larger scale are needed to evaluate the utility and safety of these drugs in labor.

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[22]
[23]
[24]
[25]
[26]
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