Tranexamic Acid Versus Misoprostol in Reducing Blood Loss in Cesarean Section in Primigravida
Tranexamic Acid Versus Misoprostol in Reducing Blood Loss in Cesarean Section in Primigravida
The aim of the work is to compare the efficacy of preoperative IV tranexamic acid and rectal
 misoprostol in reducing blood loss in the elective cesarean section.

 Research question:

 In women undergoing elective cesarean section, is preoperative administration of IV
 tranexamic acid better than rectal misoprostol in reducing blood loss?
-  Type of study: Prospective double-blinded randomized placebo-controlled Clinical trial

 -  Time plan: Approximately 12 months according to calculated sample size.

 -  study setting: this study will be conducted obstetrics and gynecology department at
 Cairo University.

 -  study population: Patients will be enrolled in this study of those attending the
 obstetric clinic at kasr el ainy hospital for elective cesarean section.

 -  Methodology:

 -  Methodology in details:

 -  Verbal and written consent will be obtained before history taking All women will be
 subjected to

 History taking:

 -  Detailed clinical history.

 -  Personal history:

 Name, Age, Parity, Occupation, Residency, and Special habits.

 -Present history: History of onset, course, and duration of vaginal bleeding or bloody
 vaginal discharge, presence of uterine contraction, PROM, IUGR, or any indication for
 cesarean section.

 -Obstetric history: History of previous abortion.

 -Menstrual history: For estimation of gestational age using Naegele's rule, provided that she
 had regular cycles for the last three months before she got pregnant and was not taking
 contraceptive pills during this period and she was sure of her dates.

 Term pregnancy defined as delivery between 37 and 42 weeks of gestation. Gestational age will
 be assessed from the menstrual history and will be confirmed by measurement of fetal
 crown-rump length at a first-trimester scan.

 -Past history: History of medical disorders, drug therapy or allergy, or history of intake of
 other tocolytic drugs.

 -Family history: For consanguinity in the case of CFMF.

 Examination

 -  Full clinical examination (pulse, temperature, and blood pressure).

 -  General examination including blood pressure, heart rate, body temperature, body mass
 index, head& neck examination, Bilateral lower limb examination, chest, heart.

 -  Local clinical examination; assessment of maternal health, obstetric abdominal
 examination for fundal level, fetal presentation, estimating fetal weight, and scars of
 previous operations, uterine contraction if present, auscultation of FHR.

 -  Preoperative investigations (Rh, CBC, HTC, Hb, Coagulation profile, fasting and
 postprandial blood sugar, and complete urine analysis).

 -  Ultrasonography examination: to assess the following data:

 -  Gestational age

 -  Fetal viability

 -  Fetal presentation and EFW.

 -  Detection of any fetal congenital anomalies.

 -  To ensure that all inclusion criteria are present.

 -  Check amniotic fluid index (the amniotic fluid index (AFI) will be estimated using
 abdominal ultrasonography on the day of delivery or the day before delivery. The uterus
 will be divided into four quadrants; the right and left quadrants will be defined by the
 linea nigra, and the upper and lower quadrants will be defined by the umbilicus. The
 maximum vertical diameter of amniotic fluid in each quadrant will be measured in
 centimeters. The sum of these four quadrants will be used to calculate the AFI. The
 volume of amniotic fluid in ml. will be estimated by multiplying the AFI by 30.

 Intervention:

 The cesarean section will be done by a senior registrar who performed at least 300 cesarean
 sections before the start of the study. All CS will be performed using spinal anesthesia; the
 abdomen will be entered by Pfannenstiel abdominal incision.

 The allotted sealed envelope (allocation concealment will be discussed later) will be taken
 to the theatre and handed over to the anesthetist who will administrate the drug (TXA or
 Misoprostol) or the placebo to the patient without telling neither the researcher nor the
 patient the content of the envelope. With the induction of anesthesia, patients assigned to
 group 1 will receive 1 gram of TXA (kapron®, Amoun, Egypt) 10 minutes before skin incision,
 by slow intravenous injection over 10 minutes and preoperative placebo (4 tablets similar to
 misoprostol in size and shape as peroxide) will be administrated rectally. (Tranexamic acid
 injection will be prepared by diluting 1gm (10ml) TXA in 100 ml of normal saline.
 Participants are assigned to group 2 will receive 800μg rectal misoprostol (Misotac®, SIGMA,
 Egypt) immediately after urinary catheterization and before skin incision and preoperative
 placebo (10 minutes before skin incision, 10 ml of distilled water ampoules or normal saline
 by slow intravenous injection over 10 minutes).

 All women will receive 10 IU of oxytocin (syntocinon®, NOVARTIS) by slow intravenous after
 cord clamping.

 Sterilization and toweling of the patient then the standard technique of trans-peritoneal
 lower segment cesarean will be adopted. The placenta will be removed by cord traction and
 uterine compression. The uterus will be exteriorized and compressed during closure which will
 be achieved by continuous unlocked sutures in 2 layers using 2/0 polyglactin suture and 1 cm
 interval between sutures. The peritoneum and muscle will be closed by 2/0 polyglactin suture
 and the sheath will be closed by 1/0 polyglactin, and the skin will be closed by subcuticular
 suture using proline double zero suture in both groups. The estimation of blood loss will be
 started after skin incision.

 -  The linen towels will be weighted in (mg) with its cover before and after the operation
 using a highly accurate digital balance and the difference in weight between dry and
 soaked linen towels will be calculated.

 -  Blood loss during the operation will be calculated as follows:

 -  Volume of the contents of the suction bottle (ml) (A).

 -  Difference in weight of linen towels (gm) (B) (weight of soaked linen towels (gm) - the
 weight of dry linen towels (gm)).

 -  Amniotic fluid volume (ml) (C).

 -  So, blood loss during operation (ml) = (A + B) - C.

 -  Allowable blood loss will be calculated for all women according to the underlying law.

 ABL= EBV x (Hi - Hf) / Hi

 Hi = initial Hct Hf = final lowest acceptable Hct Estimated Blood Volume (EBV) EBV = weight
 (kg) X average blood volume (75-85 ml/kg)

 -  A trained nurse will be responsible for the collection of wound dressing placed in the
 vulval area during the first 24 hours after surgery and the difference in weight will be
 calculated. The overall blood loss will be calculated.

 -  The difference between preoperative and 24 hours postoperative in hemoglobin
 concentration and hematocrit value will be measured to calculate allowable blood loss

 -  The need for additional uterotonics drugs will be given according to the attendant
 consultant decision or a blood loss of more than 1000ml intraoperative.

 -  Operative time, need for blood transfusion and side effects of study drug e.g. nausea,
 vomiting, diarrhea will be recorded.

 -  All the patients will receive non-steroidal anti-inflammatory preparation in the form of
 (Rheumarene®) 75mg IM (one ampoule) immediately postoperative than one ampoule 12 hours
 postoperative and the need for extra analgesics will be recorded.

 -  All the patients will receive prophylactic broad-spectrum antibiotics in form of
 (Ceftriaxone®, Sandoz, Egypt) 1 gm./12 hours.

 -  The Apgar score of the fetus at 1 and 5 minutes, the need for neonatal intensive care
 unit (NICU) admission, and neonatal death will be assessed in the two groups.

 -  Data will be collected, tabulated, and statistically analyzed by IBM computer using the
 Statistical Package for the Social Sciences (SPSS version 24). Chi-square test will be
 used to compare qualitative variables between groups and Fisher exact test will be used
 instead of the Chi-square test when the expected cell count less than 5. The student
 t-test will be used to compare the quantitative variables in parametric data. P-value
 <0.05 will be set signiﬁcant.
Inclusion Criteria:

 -  Women booked for a primary elective cesarean section, not in active labor

 -  Aged between 18-40 years.

 -  BMI 18.5-29.9 kg/ m2 pre-pregnancy weight

 -  Term pregnancies (Early term: between 37 weeks, 0 days and 38 weeks, 6 days. Full
 term: between 39 weeks, 0 days and 40 weeks, 6 days. Late term: between 41 weeks, 0
 days and 41 weeks, 6 days).

 -  Singleton pregnancies.

 -  Indication of elective cesarean section (Malpresentation, Malposition, Cephalopelvic
 disproportion, active herpes)

 -  Fetal macrosomia (Macrosomia is defined as birth-weight over 4,000 g irrespective of
 gestational age)

 -  Certain congenital fetal malformation and skeletal disorders (Several congenital
 anomalies are controversial indications for cesarean delivery; these include fetal
 neural tube defects (to avoid sac rupture), particularly defects that are larger than
 5-6 cm in diameter as anterior cystic hygroma vascular sacrococcygeal teratoma, giant
 omphalocele and hydrocephalus with an enlarged biparietal diameter, and some skeletal
 dysplasia such as type III osteogenesis imperfecta. (Hamrick et al., 2008)

 Exclusion Criteria:

 -  Placenta previa.

 -  Maternal hypertension and Preeclampsia.

 -  Diabetes mellitus.

 -  Severe medical disorder (renal or hepatic).

 -  Multiple Fibroid uterus.

 -  Multiple pregnancies.

 -  Polyhydramnios.

 -  Previous uterine surgery as myomectomy.

 -  Contraindication to spinal anesthesia.

 -  Blood coagulopathy and bleeding disorder.

 -  Marked maternal anemia (Preoperative hemoglobin <9 gm/dl).

 -  Contraindications to prostaglandin therapy (e.g. history of severe bronchial asthma or
 allergy to misoprostol) or TXA