Effect of oral nifedipine or combined with sildenafil.pptx

Oral nifedipine vs combined nefidipine and slidenafil

1. Effect of oral nifedipine or combined with sildenafil citrate for management of threatened preterm labour randomized trial Moderator – Dr. Kavita M Bhatti Presentor – Dr. Cyril Thomas

2. Overview – Pre-term Labor is the onset of regular painful uterine contractions with effacement and dilatation of the cervix prior to the completion of 37 weeks of pregnancy. Threatened preterm labor occurs when regular uterine contractions occur at least once every 10 minutes and last for more than 30 minutes before the 37t h week of pregnancy without the cervix dilation causes 75% of neonatal mortality and 50% of long-term morbidities such as respiratory distress and neurodevelopmental impairment. main goal of obstetrician is to delay delivery for at least 24-48 hours in order to give adequate time for corticosteroids to be administered which aids in lowering the newborn complications.

3. DRUG DRUG DESCRIPTION Indomethacin A nonsteroidal anti-inflammatory (NSAID) used for symptomatic management of chronic musculoskeletal pain conditions and to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants. Magnesium sulfate used to treat convulsions during pregnancy, nephritis in children, magnesium deficiency, and tetany . Orciprenaline A beta-2 adrenergic agonist used to treat bronchospasm, asthma, and COPD. Ritodrine An adrenergic beta agonist used to treat premature labor. Terbutaline A beta-2 adrenergic agonist used as a bronchodilator and to prevent premature labor. Salbutamol A beta-2 adrenergic receptor agonist used to treat asthma, bronchitis, COPD, as well as prevent exercise induced bronchospasms. Nifedipine A dihydropyridine calcium channel blocker indicated for the management of several subtypes of angina pectoris, and hypertension. Fenoterol A beta-2 adrenergic agonist and bronchodilator used for the symptomatic treatment of asthma. Nylidrin A vasodilator used to treat patients with peripheral vascular disorders, and elderly patients with symptoms associated with organic mental disorders. Isoxsuprine A beta-adrenergic agonist used in the symptomatic treatment of cerebrovascular insufficiency, peripheral vascular disease of arteriosclerosis obliterans , thromboangiitis obliterans ( Buerger's disease) and Raynaud's disease. Drugs used in – Pre-term labor

4. Sildenafil phosphodiesterase type 5 inhibitor affects uteroplacental perfusion . inhibits phosphodiesterase type 5 (PDE5), an enzyme responsible for degradation of nitric oxide, and its efficacy is greater in the placental territory, as the maternal side of the placenta have more PDE5 than other sites. can improve fetoplacental perfusion in pregnancies complicated by intrauterine growth restriction. It could be a potential therapeutic strategy to improve uteroplacental blood flow in pregnancies with fetal growth restriction (FGR ).   pharmacokinetic data suggest 25-50 mg of Sildenafil administered orally as the initial dose for most patients.  

5. Study (year) Population (n) Intervention—Sildenafil (n) Control—Placebo (n) Analyzed outcomes Follow up time Samangaya (2009) 20 Women with pre-eclampsia and gestational age between 24 and 34 weeks. (39) Sildenafil 20 to 80 mg oral daily, (19) Placebo orally. (20) Fetal weight at birth, indication of pregnancy resolution, umbilical artery PI, neonatal mortality, and side effects. From recruitment to the day of birth. Von Dadelszen (2011) 23 Pregnant women with severe early onset intrauterine growth restriction. (27) Sildenafil 25 mg every 8 hours orally from recruitment to the day of birth. (10) Placebo orally. (17) Gestational age at birth, neonatal mortality, and side effects. From recruitment to the day of birth. Dastjerdi (2012) 22 Pregnant women with intrauterine growth restriction—percentile 3. (59) Oral sildenafil 50 mg, one single dose. (29) Placebo orally, one single dose. (30) Umbilical artery pulsatility index (PI), neonatal mortality and side effects. No follow up. Trapani (2016) 21 Women with pre-eclampsia and single gestation between 24 and 33 weeks of gestation. (100) Sildenafil 50 mg every 8 hours orally from recruitment to the day of birth. (50) Placebo orally. (50) Fetal weight at birth, indication of pregnancy resolution, umbilical artery PI, neonatal mortality, and side effects. From recruitment to the day of birth. El Sayed (2017) 24 Pregnant women with fetal growth restricition due to placental insufficiency with 24 weeks or more. (54) Oral sildenafil 50 mg, daily. (27) Placebo orally. (27) Fetal weight at birth, gestational age at birth, umbilical artery PI, neonatal mortality, and side effects. From recruitment to the day of birth. Maher (2017) 26 Pregnant women with oligohydramnios (ILA <5 cm), older than 30 weeks. (184) Sildenafil 25 mg orally every 8 hours and intravenous hydration. (89) Intravenous hydration. (95) Fetal weight at birth, neonatal mortality, and side effects. From recruitment to the day of birth. Sharp (2018) 25 Pregnant women with fetal growth restriction (percentile <10) and absent or reversed end-diastolic flow in umbilical artery on Doppler, from 22 to 29 weeks and 6 days. (135) Sildenafil 25 mg every 8 hours orally from recruitment to 32 weeks or birth (70) Placebo orally. (65) Fetal weight at birth, gestational age at birth and neonatal mortality. From recruitment to the day of birth.

6. Research article “ Effect of oral nifedipine or combined with sildenafil citrate for management of threatened preterm labour randomized trial ” by – Dr.Shreya Singh, Dr.Sheela S Conducted at Sri Devaraj Urs Academy of Higher Education and Research, Kolar , Karnataka, India

7. Objective To assess the efficacy of nifedipine combined with sildenafil citrate in preventing the progress of threatened preterm labor. To evaluate the efficacy of nifedipine alone for preventing the progress of uterine contraction in threatened preterm labor. To determine the maternal and perinatal outcome among the groups using nifedipine alone and nifedipine combined with sildenafil citrate.

8. Materials and Methods Study population All the eligible pregnant women admitted to labor room with threatened preterm labor at R.L JALAPPA Hospital attached to Sri Devaraj Urs Medical College were considered as the study population. Study design Randomized Trial Group A: Nifedipine Group B: Sildenafil+Nifedipine Sample size required sample size was calculated using the following formula as proposed by Kirkwood BR et al s required sample size as per the above-mentioned calculation was 26 in each group. To account for a non-participation rate/loss-to-follow-up rate of about 11%, another 4 subjects will be added to sample size. Hence, the final required sample size would be 30 subjects in each group

9. Materials and Methods Study duration The data collection was done between January 2020-June 2021 for a period of 1 year 5 months. Inclusion criteria Age : 18-35 years gestational age 28-37 weeks. Singleton pregnancy. No vaginal discharge. Exclusion criteria Cervical dilatation Cervical length>15mm on TVS Chorioamnionitis (unexplained fetal tachycardia or maternal temperature) Maternal complications like eclampsia , HELLP syndrome Bronchial asthma, cardiac or thyroid disorder.

10. Methdology Pregnant women hospitalized to labor room were recruited for the study General examination includes 1 . Maternal pulse rate. 2 . Blood pressure. 3 . Uterine contraction. 4 . Fetal heart rate. 4.12 . Routine examination 1 . Complete blood count. 2 . Serology: HIV and Hepatitis-B. 3 . Bleeding time. 4 . Clotting time. 5 . Random blood sugar. 6 . Transvaginal ultrasound- cervical length more than 15 mm, diagnostic for preterm labor .

11. Methodology Chit system randomization by chit system. Chit system was F irst group had received nifedipine alone Second group had received nifedipine along with sildenafil citrate per vaginal . Nifedipine 20mg orally stat dose followed by 10mg orally every 6-8hours at the same time as vaginal administration of sildenafil citrate 25mg at 8t h hourly interval every 6-8hrs. Each woman was followed up until delivery, and the outcome was recorded. The success of tocolysis was considered at the end of 48hours, after the onset of tocolysis Tocolysis was considered as failed if uterine quiescence was not stopped, despite a maximum dose of delivery or when the patient delivered within 48hours of initiation of therapy.

12. STASTICAL METHODS Maternal side effects and neonatal outcomes were considered as primary outcome variables. The study group (Group-A vs. Group-B) was considered as the primary explanatory variable. Skewed distributed quantitative variables were summarized by the median and interquartile range. Data was also represented using appropriate diagrams like Error bar diagram, Stacked bar diagram, and cluster bar diagram. All Quantitative variables were checked for normal distribution. For normally distributed Quantitative parameters, mean values were compared between study groups using an independent sample ttest (2-groups). For non-normally-distributed Quantitative parameters, Medians and Interquartile range (IQR) were compared between study groups using Mann Whitney u test (2-groups). Categorical outcomes were compared between study groups using the Chi-square test/Fisher’s Exact test (If overall sample size was <20 or if expected number in any one of the cells is <5, Fisher’s exact test was used.). P-value<0.05 was considered statistically significant. Data were analyzed by using coGuide software, V.1.03

13. Result final analysis comprised a total of 60 subjects. Group A ( Nifedipine ) were 30 participants, and Group B ( Sildenafil+Nifedipine ) were 30 participants Gestational age Causes of preterm

14. RESULT Maternal Side-effects Birth weight

15. RESULT Neonatal complications Comparison of Loading Dose

16. RESULT Final outcome

17. Discussion Mean age of the study Group A - 21.07±3.31 Group B - 22.87±3.15 Above studies showed an increased mean of age compared to their study . In the present study, majority of the participants in both the groups belonged to early 20s. Gravida Present study- Primigravida – Group A – 86.67% , Group B – 73.33% Urmila Karya et al – Group A – 35 % Group B – 37.5 % More participants were primi gravida Study name Group A Group B Shoukat F et al. 30.67±3.90 29.95±4.32 Yousef Abou-Elwan El- Sayed et al 30.6±4.9 31.3±6.1 Elkattan R. et al 26.75 26.55

18. Discussion History of preterm Median prolongation of pregnancy Current Study - 2(2,5) days in group A & 7(2.75,20) in group B Saima Ayub et al – prolongation o f pregnancy between 48hours-1week in nifedipine group with 37.50% followed by >1week with 30.68% while, in sildenafil group majority of the women had >1week prolongation of pregnancy with 32.95% followed by 48hours-1week with 20.65% similar to their study Study Group A Group B Present study 40% 75% In Elham Mohammadi et al 9.1% 21.2%

19. Discussion Maternal Side-effects Comparable to their study Side-effects Group A Group B Present Study Palpitation 3.33% 10% Tachycardia 26.67% 10% Nausea & Vomitting 16.67% - Facial flushing - 6.67% Headache - 6.67% Urmila Karya et al. Facial flushing 22.5% 42.5% Palpitations 10% 7.5% Headache 25% 40% Nausea 7.5% 5%

20. Discussion Mean birth weight Mean birth weight is more in their study Cervical Length Decreased mean compared to their study Group A Group B Current Study 2090±372.64 2381.67±492.44 Elham Mohammadi et al 1609.0±204.3 2154.5±221.3 Group A Group B Cervical score length btw 31 and 36 Current Study 90% 93.3% Elham Mohammadi et al. 29.50cm 28.62cm

21. Discussion Neonatal outcomes Group A Group B Present Study Respiratory Distress syndrome 16.67 23.33 NICU admission 23.33 36.67 Perinatal death 20 3.33 Alive and well 53.33 56.67 Urmila Karya et al. Respiratory distress 22.5 10 Perinatal death 35 22.5 Abd El- Naser et al. Respiratory distress 7.40 8.30 Sepsis 4.20 4.10 Perinatal death 1.06 2.08

22. RESULTS ideal tocolytic agent should be safe, well tolerated, easily administered, rapidly absorbed and should relax myometrium to prevent threatened preterm labor. Effect of tocolytic is intensified through the synergistic effect of sildenafil citrate with nifedipine combination. In their study, a combination of sildenafil citrate and nifedipine was found to be more beneficial than nifedipine alone. The combination has better efficacy in maternal and neonatal outcome, compared to nifedipine alone

23. Thank You