- Email: [email protected]
Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given pre- and post-operative after elective cesarean section
Middle East Fertility Society Journal (2014) 19, 8–12
Middle East Fertility Society
Middle East Fertility Society Journal www.mefsjournal.org www.sciencedirect.com
OPINION ARTICLE
Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given pre- and post-operative after elective cesarean section Ahmed H. Abd-Ellah, Abdel Aziz E. Tamam, Mostafa Mohammed Khodry
*
Department of Obstetrics & Gynecology, Faculty of Medicine, South Valley University, Qena, Egypt Received 13 June 2013; accepted 22 September 2013 Available online 22 October 2013
KEYWORDS Cesarean section; Misoprostol; Blood loss; Uterotonic drugs; Pre-operative; Post-operative
Abstract Objective: The aim of the current study was to compare blood loss in pre- and postoperatively rectally administered 600 lg of misoprostol in elective cesarean delivery, in order to determine the optimal time for drug administration (CS). Study design: A 30-month prospective, single-blind, randomized, clinical trial was done in the Qena University Hospital, Egypt, from January 2010 to October, 2012. Methods: Intervention consisted of pre and post-operative rectally administered misoprostol. At baseline, there were no significant differences in the demographic and obstetric variable between groups. Primary outcome measures were differences in intra-operative and postoperative blood loss between groups. Secondary outcomes measures were hemoglobin levels pre and operative (24 h after CS) and the need for additional uterotonic drugs. Results: A total of 300 subjects were enrolled (pre-operative administrated rectally misoprostol n = 150, post-operative administrated rectally misoprostol n = 150). Subjects receiving pre-operative misoprostol achieved significantly lower blood loss compared to those receiving post-operative misoprostol (620 ± 291 ml vs. 898 ± 321 ml, p < 0.05), respectively. The need for additional uterotonic was significantly higher in subjects receiving post-operative misoprostol compared to those receiving pre-operative misoprostol (53.3% vs. 30%, p, 0.05), respectively. Conclusion: Pre-operative rectally administrated misoprostol appears to be more effective than post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need for other uterotonic drugs in cesarean section delivery. Ó 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.
* Corresponding author. Tel.: +20 1007088098. E-mail address: [email protected] (M.M. Khodry). Peer review under responsibility of Middle East Fertility Society.
Production and hosting by Elsevier
1. Introduction Cesarean section is one of the most commonly performed major operations in women throughout the world. Postpartum hemorrhage (PPH) is defined as a blood loss of more than
1110-5690 Ó 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. http://dx.doi.org/10.1016/j.mefs.2013.09.002
Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given 1000 ml in the first 24 h. following cesarean section. Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, and the number of maternal deaths due to postpartum hemorrhage is estimated to exceed 100,000 maternal deaths each year (1). Misoprostol is a synthetic PGE1 analogue, owing to its uterotonic properties; it is now one of the most popular drugs in obstetrics (2). The low cost of drug, safety, stability, and the ease of administration through multiple routes make it a good option in poor setting and in patients who are vomiting or under anesthesia (3). The drug was proved to be effective in reducing blood loss when administered orally, buccally and rectally in many previous studies (4,5). However, the optimal time of drug administration has not been addressed in these previous studies. The current study was set to compare blood loss in pre- and post-operatively rectally administered 600 lg of misoprostol in elective cesarean delivery, in order to determine the optimal time for drug administration. 2. Materials and methods This is a prospective, randomized; single-blind controlled clinical study was conducted at the department of Obstetrics & Gynecology, Qena University Hospital from January 2010 to October, 2012. The study was approved by the Ethics Committee of Qena University Hospital, Egypt. The total number of elective CS during the study period was 358. Of these; 305 women met the inclusion criteria who were randomly allocated into two groups by using computer generated tables. Group 1, women receiving pre-operatively rectally administered 600 lg of misoprostol (n = 153) and Group 2, women receiving post-operative 600 lg of misoprostol (n = 152). Three women were lost to follow-up in group 1, and 2 women were lost to follow-up in the group 2 and finally 300 women were enrolled (150 subjects in each group) in both groups (Figure 1). 2.1. Inclusion criteria Patients included in the study were those not in active labor, had reactive non-stress test, had no hypersensitivity or contraindications to prostaglandins, and had no history of coagulopathy. 2.2. Exclusion criteria The reasons for exclusion were placenta previa, maternal hypertension, diabetes mellitus and previous CS and those with active labor. Patients who met the inclusion criteria were subjected to clinical evaluation, and laboratory investigations such as complete blood picture, urine analysis, blood sugar and coagulation profile (including prothrombin time, and partial thromboplastin time). Sonographic evaluation was offered to all study subjects with special emphasis on placental localization, estimated of the expected date of delivery and biophysical profile. Group 1, included 153 patients who received 600 lg misoprostol rectally after spinal anesthesia and urinary bladder catheterization (3 tablets each 200 lg) and Group 1 included 152 patients who received 600 lg misoprostol rectally postoperatively on the operating theater (3 tablets each 200 lg). Cesarean section delivery was done under spinal anesthesia by senior obstetricians who were blind to allocation. The
9
placenta was delivered by cord clamping and uterine compression. The uterus was closed in situ in continuous unlocked suture in 2 layers using Vicryl 1 suture (Johnson & Johnson, USA). The peritoneum and muscle was closed by Vicryl 0 suture. The sheath was closed by Vicryl 1, and the skin was closed by subcutical suture using proline double zero suture in both groups. Estimation of blood loss was started after skin incision. A dedicated nurse was responsible for collection of blood and amniotic fluid in two separate suction sets and weighting surgical towels before and after the operation. Post partum blood loss during the first 24 h after the operation was assessed by weighting soaked napkins. Preoperative hemoglobin was measured 2 h before surgery and assessed 24 h after the operation. The neonatal outcome including; Apgar score, the need for neonatal intensive care unit (NICU) admission and neonatal death were assessed in the two groups. The drug side effects as regards post operative fever, vomiting and shivering were compared in both groups. Data were collected and tabulated and statistically analyzed by IBM computer using the Statistical Package for the Social Sciences (SPSS version 15). Chi-square test was used to compare qualitative variables between groups and Fisher exact test was used instead of Chisquare test when the expected cell count is less than 5. Student t-test was used to compare the quantitative variables in parametric data. p value < 0.05 was set significant. 3. Results There were no significance differences between both groups as regards age, parity, body mass index, and gestational age, and preoperative hemoglobin level (Table 1). The mean blood loss during and after CS delivery was significantly lower in the preoperatively rectally administered misoprostol group (620 ± 291) when compared to the post-operative rectally administered misoprostol group (898 ± 321) and this difference was statistically significant with p value < 0.05. The need for additional uterotonic was significantly higher in the preoperatively rectally administered misoprostol group than the post-operative rectally administered misoprostol group (53.3% vs. 30%, p < 0.05), respectively (Table 2). Postoperative hemoglobin level (24 h) was significant lower in the postoperative rectally administered misoprostol group, (9.8 ± 1.24) than the pre-operatively rectally administered misoprostol group (10.5 ± 1.31) with p value 0.034. However, the change in Hb level between the preoperative level and post operative level was obviously higher in the post-operative rectally administered misoprostol group (1.9 ± 0.45) than the pre-operatively rectally administered misoprostol group (1.2 ± 0.67) (p = 0.032). The neonatal outcomes and drug side effects were nearly comparable in both groups as regards the Apgar score at 1 and 5 min, need for neonatal intensive care admission, post operative fever, shivering and vomiting in both groups (Table 3). 4. Discussion Prophylactic administration of misoprostol rectally after cesarean delivery is increasing nowadays to decrease blood loss after CS delivery. To the best of our knowledge, this is the first study that compares preoperative and post-operative rectally administrated misoprostol in reducing blood loss at cesarean
10
A.H. Abd-Ellah et al. Total number of elecve CS (n=358) "Excluded (n =53) • •
Did not meet inclusion criteria (n=43) Refused parcipaon (n=10)
Consented to parcipate (n=305)
Randomizaon
Allocated to Pre-operave rectally administrated misoprostol
Allocated to post-operave rectally administrated misoprostol
Lost to flow-up
Lost to flow-up (n=3)
(n=2)
Analyzed (n=150)
Figure 1
Table 1
Analyzed (n=150)
Flow chart of the study design.
Patients characteristics of the study groups.
Age (years) Parity Body mass index Gestational age Preoperative Hb level
Study group (N = 150)
Control group (N = 150)
p value
24.7 ± 4 3.20 ± 1.1 21 ± 0.8 39.4 ± 0.8 11.8 ± 3.6
25.08 ± 3.9 3.5 ± 1.9 22 ± 0.6 39.1 ± 0.9 11.6 ± 4.8
0.542 0.461 0.442 0.58 0.48
Values presented by mean ± SD, p value < 0.05 was set be significant.
section. Reduction of operative blood loss at cesarean section is beneficial to patients in terms of decreased postoperative morbidity and a decrease in risks associated with blood transfusions (6). Misoprostol, a PGE1 analogue, has been investigated both for prevention and management of PPH due to its uterotonic effect. However, there is no general consensus on the optimal time, dose or route of administration (7). Rectally administered misoprostol has the advantage of a slower absorption rate, lower concentration level and consequently lower adverse effects (8) compared to Sublingual misoprostol, which has the greatest bioavailability among all routes of administration and a higher incidence of complications (6). On the other hand, oral route has the highest side effects (8,9). For these reasons, the rectal route was the preferred route of administration in the present study. The current study used 600 lg of misoprostol which was administered rectally in
both groups after catheter insertion and before draping to allow time for absorption and action to occur. Because we are comparing the optimal time for misoprostol administration, other uterotonic drugs were instituted when intra-operative or post-operative bleeding exceeded 500 ml. In the current study, the mean blood loss during and after CS delivery was significantly lower in the pre-operative rectally administered misoprostol group compared to those receiving misoprostol post-operatively. This can be explained by the fact that, high availability and higher concentration of misoprostol had occurred after the end of the surgical procedure, hence leading to strong uterine contraction and consequently resulted in the reduction of blood lost. Further study is warranted to determine the concentration of misoprostol in the blood in both groups following the end of the procedure. A randomized controlled trial using 400 lg was conducted to evaluate the im-
Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given Table 2
11
Primary outcome measures in the two studied groups.
Characteristics
Study group (n = 150)
Control group (N = 150)
p value
Blood loss ML Need for uterotonic drug No need Need Mean Hb level((g/dl) Postoperative 24 h Change in Hb
620 ± 291
898 ± 321
0.003
105 (70) 45 (30)
70 (46.7) 80 (53.3)
0.023
10.5 ± 1.31 1.2 ± 0.67
9.8 ± 1.24 1.9 ± 0.45
p < 0.05 0.032
Values are presented as (Mean ± SD), number (percentage), p value < 0.05 was set be significant.
Table 3
Fetal and drug adverse effect in both groups.
Apgar score at 5 min Meconium aspiration NICU admission Pyrexia Shivering Vomiting
Study group (N = 100)
Control group (N = 100)
p value
9.74 ± 0.66 8 ± 0.42 7 ± 0.31 15 (15%) 20 (20%) 7 (7%)
9.88 ± 0.60 6 ± 0.56 7 ± 0.42 17 (17%) 18 (18%) 11 (11%)
>0.05 >0.05 >0.05 >0.05 >0.05 >0.05
pact of preoperative administration of rectal misoprostol on blood loss among 400 women undergoing elective cesarean delivery and concluded that, preoperative treatment with 400 lg rectal misoprostol significantly reduced blood loss (10). Most of the relevant studies supported the view that rectally administered misoprostol is better than other uterotonic drugs in reducing blood loss specially if administered rectally (11). In the present study, post-operative Hb level (after 24 h) was significantly lower in the post-operative rectally administered misoprostol (9.8 ± 1.24 g/dl) than pre-operatively administered group (10.5 ± 1.31 g/dl), p < 0.05. This finding agrees with results obtained by Elsedeek who concluded that, pre-operative rectally administered misoprostol after elective CS resulted in a significantly higher Hb level and hematocrit values in rectally administered misoprostol than placebo (10). Pre-operative misoprostol was used via oral (12) and sublingual routes for different operations for blood reduction which was reported to be effective in reducing blood loss during surgery (13). The additional need for other uterotonic drugs to control blood loss during CS delivery was markedly noticed in women who received post-operative misoprostol (n = 80, 53.3%) compared to women who received pre-operative misoprostol (n = 4530%), p < 0.05 respectively. Again, this finding is in agreement with the results of Elseedeek (10) who mention in their studies that the percentage of women requiring additional oxytocics was significantly higher in the control group than in the study group (10). Jennifer et al., 2005, reported the same findings however, in their study they used the buccal route, not the rectal route for drug administration (11). In this study, there was no clinically significant difference in the neonatal outcomes in both groups as regards the timing of administration of the drug and this agrees with the results obtained by Elsedeek (10) who reported that the preoperative administration of the misoprostol rectally did not cause any fetal adverse effects in the study group.
5. Conclusion Pre-operative rectally administrated misoprostol appears to be more effective than post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need for other uterotonic drugs in cesarean section delivery. Conflict of interest We declare no conflict of interest. References (1) Mousa H, Alfirevic Z. Treatment for primary postpartum hemorrhage (Cochrane review). Chichcster (UK): John Wiley & Sons Ltd. The Cochrane Library; 2009, Issue 4. (2) Chong Y, Sull A, Arulkumaran S. Current strategies for the prevention of postpartum hemorrhage in the third stage of labor. Curr Opin Obstet Gynecol 2004;16(2):143–50. (3) Derman R, Kodkany B, Goudar S, Geller S, Naik V, Belied M, et al. Oral misoprostol in preventing postpartum hemorrhage in resource-poor communities: a randomized controlled trail. Lancet 2006;368(9543):124–53. (4) Tang O, Schwer H, Eberth H. Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod 2002;17:332–6. (5) Picklu C, Gita B, Apurba. Rectally administrated misoprostol versus intravenous oxytocin infusion during cesarean delivery to reduce intraoperative and postoperative blood loss. Int J Gynaecol Obstet 2010;109(1 (April)):25–9. http://dx.doi.org/10.1016/ j.ijgo.2009.11.00, Epub 2010 January 13. (6) Lapaire O, Schneider MC, Stotz M, Surbek DV, Holzgreve W, Hoesli IM. Oral misoprostol vs. intravenous oxytocin in reducing blood loss after emergency cesarean delivery.. Int J Gynaecol Obstet 2006;95(1 (October)):2–7, Epub 2006 August 23. (7) El-Refaey H, Rodeck C. Postpartum hemorrhage: definitions, medical and surgical management. A time for change. Br Med Bull 2003;67:205–17.
12 (8) Tang OS, Ho PC. The pharmacokinetics and different regimens of misoprostol in early first-trimester medical abortion. Contraception 2006;74(1):26–30. (9) Khan RU, El-Refaey H. Pharmacokinetics and adverse-effect profile of rectally administered misoprostol in the third stage of labor. Obstet Gynecol 2003;101(5 Pt 1):968–74. (10) Elsedeek MS. Impact of preoperative rectal misoprostol on blood loss during and after elective cesarean delivery. Int J Gynaecol Obstet 2012;118(2 (August)):149–52. http://dx.doi.org/10.1016/ j.ijgo.2012.03.038, Epub 2012 June 13. (11) Chaudhuri P, Banerjee GB, Mandal A. Rectally administered misoprostol versus intravenous oxytocin infusion during cesarean
A.H. Abd-Ellah et al. delivery to reduce intraoperative and postoperative blood loss. Int J Gynecol Obstet 2010;109(1):25–9. (12) El Tahan MR, Warda OM, Rashad A, Yasseen AM, Ramzy EA, Ahmady MS, Diab DG, Matter MK. Effects of preoperative sublingual misoprostol on uterine tone during isoflurane anesthesia for cesarean section. Rev Bras Anestesiol 2012; 62(5 (September)):625–35. http://dx.doi.org/10.1016/S0034-7094 (12)70162-9. (13) Ercan CM, Coksuer H, Karasahin KE, Alanbay I, Aydogan U, Parlak A, Baser I. Comparison of different preoperative sublingual misoprostol regimens for surgical termination of first trimester pregnancies: a prospective randomized trial. J Reprod Med 2011;56(5–6 (May–June)):247–53.
Middle East Fertility Society
Middle East Fertility Society Journal www.mefsjournal.org www.sciencedirect.com
OPINION ARTICLE
Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given pre- and post-operative after elective cesarean section Ahmed H. Abd-Ellah, Abdel Aziz E. Tamam, Mostafa Mohammed Khodry
*
Department of Obstetrics & Gynecology, Faculty of Medicine, South Valley University, Qena, Egypt Received 13 June 2013; accepted 22 September 2013 Available online 22 October 2013
KEYWORDS Cesarean section; Misoprostol; Blood loss; Uterotonic drugs; Pre-operative; Post-operative
Abstract Objective: The aim of the current study was to compare blood loss in pre- and postoperatively rectally administered 600 lg of misoprostol in elective cesarean delivery, in order to determine the optimal time for drug administration (CS). Study design: A 30-month prospective, single-blind, randomized, clinical trial was done in the Qena University Hospital, Egypt, from January 2010 to October, 2012. Methods: Intervention consisted of pre and post-operative rectally administered misoprostol. At baseline, there were no significant differences in the demographic and obstetric variable between groups. Primary outcome measures were differences in intra-operative and postoperative blood loss between groups. Secondary outcomes measures were hemoglobin levels pre and operative (24 h after CS) and the need for additional uterotonic drugs. Results: A total of 300 subjects were enrolled (pre-operative administrated rectally misoprostol n = 150, post-operative administrated rectally misoprostol n = 150). Subjects receiving pre-operative misoprostol achieved significantly lower blood loss compared to those receiving post-operative misoprostol (620 ± 291 ml vs. 898 ± 321 ml, p < 0.05), respectively. The need for additional uterotonic was significantly higher in subjects receiving post-operative misoprostol compared to those receiving pre-operative misoprostol (53.3% vs. 30%, p, 0.05), respectively. Conclusion: Pre-operative rectally administrated misoprostol appears to be more effective than post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need for other uterotonic drugs in cesarean section delivery. Ó 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.
* Corresponding author. Tel.: +20 1007088098. E-mail address: [email protected] (M.M. Khodry). Peer review under responsibility of Middle East Fertility Society.
Production and hosting by Elsevier
1. Introduction Cesarean section is one of the most commonly performed major operations in women throughout the world. Postpartum hemorrhage (PPH) is defined as a blood loss of more than
1110-5690 Ó 2013 Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society. http://dx.doi.org/10.1016/j.mefs.2013.09.002
Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given 1000 ml in the first 24 h. following cesarean section. Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, and the number of maternal deaths due to postpartum hemorrhage is estimated to exceed 100,000 maternal deaths each year (1). Misoprostol is a synthetic PGE1 analogue, owing to its uterotonic properties; it is now one of the most popular drugs in obstetrics (2). The low cost of drug, safety, stability, and the ease of administration through multiple routes make it a good option in poor setting and in patients who are vomiting or under anesthesia (3). The drug was proved to be effective in reducing blood loss when administered orally, buccally and rectally in many previous studies (4,5). However, the optimal time of drug administration has not been addressed in these previous studies. The current study was set to compare blood loss in pre- and post-operatively rectally administered 600 lg of misoprostol in elective cesarean delivery, in order to determine the optimal time for drug administration. 2. Materials and methods This is a prospective, randomized; single-blind controlled clinical study was conducted at the department of Obstetrics & Gynecology, Qena University Hospital from January 2010 to October, 2012. The study was approved by the Ethics Committee of Qena University Hospital, Egypt. The total number of elective CS during the study period was 358. Of these; 305 women met the inclusion criteria who were randomly allocated into two groups by using computer generated tables. Group 1, women receiving pre-operatively rectally administered 600 lg of misoprostol (n = 153) and Group 2, women receiving post-operative 600 lg of misoprostol (n = 152). Three women were lost to follow-up in group 1, and 2 women were lost to follow-up in the group 2 and finally 300 women were enrolled (150 subjects in each group) in both groups (Figure 1). 2.1. Inclusion criteria Patients included in the study were those not in active labor, had reactive non-stress test, had no hypersensitivity or contraindications to prostaglandins, and had no history of coagulopathy. 2.2. Exclusion criteria The reasons for exclusion were placenta previa, maternal hypertension, diabetes mellitus and previous CS and those with active labor. Patients who met the inclusion criteria were subjected to clinical evaluation, and laboratory investigations such as complete blood picture, urine analysis, blood sugar and coagulation profile (including prothrombin time, and partial thromboplastin time). Sonographic evaluation was offered to all study subjects with special emphasis on placental localization, estimated of the expected date of delivery and biophysical profile. Group 1, included 153 patients who received 600 lg misoprostol rectally after spinal anesthesia and urinary bladder catheterization (3 tablets each 200 lg) and Group 1 included 152 patients who received 600 lg misoprostol rectally postoperatively on the operating theater (3 tablets each 200 lg). Cesarean section delivery was done under spinal anesthesia by senior obstetricians who were blind to allocation. The
9
placenta was delivered by cord clamping and uterine compression. The uterus was closed in situ in continuous unlocked suture in 2 layers using Vicryl 1 suture (Johnson & Johnson, USA). The peritoneum and muscle was closed by Vicryl 0 suture. The sheath was closed by Vicryl 1, and the skin was closed by subcutical suture using proline double zero suture in both groups. Estimation of blood loss was started after skin incision. A dedicated nurse was responsible for collection of blood and amniotic fluid in two separate suction sets and weighting surgical towels before and after the operation. Post partum blood loss during the first 24 h after the operation was assessed by weighting soaked napkins. Preoperative hemoglobin was measured 2 h before surgery and assessed 24 h after the operation. The neonatal outcome including; Apgar score, the need for neonatal intensive care unit (NICU) admission and neonatal death were assessed in the two groups. The drug side effects as regards post operative fever, vomiting and shivering were compared in both groups. Data were collected and tabulated and statistically analyzed by IBM computer using the Statistical Package for the Social Sciences (SPSS version 15). Chi-square test was used to compare qualitative variables between groups and Fisher exact test was used instead of Chisquare test when the expected cell count is less than 5. Student t-test was used to compare the quantitative variables in parametric data. p value < 0.05 was set significant. 3. Results There were no significance differences between both groups as regards age, parity, body mass index, and gestational age, and preoperative hemoglobin level (Table 1). The mean blood loss during and after CS delivery was significantly lower in the preoperatively rectally administered misoprostol group (620 ± 291) when compared to the post-operative rectally administered misoprostol group (898 ± 321) and this difference was statistically significant with p value < 0.05. The need for additional uterotonic was significantly higher in the preoperatively rectally administered misoprostol group than the post-operative rectally administered misoprostol group (53.3% vs. 30%, p < 0.05), respectively (Table 2). Postoperative hemoglobin level (24 h) was significant lower in the postoperative rectally administered misoprostol group, (9.8 ± 1.24) than the pre-operatively rectally administered misoprostol group (10.5 ± 1.31) with p value 0.034. However, the change in Hb level between the preoperative level and post operative level was obviously higher in the post-operative rectally administered misoprostol group (1.9 ± 0.45) than the pre-operatively rectally administered misoprostol group (1.2 ± 0.67) (p = 0.032). The neonatal outcomes and drug side effects were nearly comparable in both groups as regards the Apgar score at 1 and 5 min, need for neonatal intensive care admission, post operative fever, shivering and vomiting in both groups (Table 3). 4. Discussion Prophylactic administration of misoprostol rectally after cesarean delivery is increasing nowadays to decrease blood loss after CS delivery. To the best of our knowledge, this is the first study that compares preoperative and post-operative rectally administrated misoprostol in reducing blood loss at cesarean
10
A.H. Abd-Ellah et al. Total number of elecve CS (n=358) "Excluded (n =53) • •
Did not meet inclusion criteria (n=43) Refused parcipaon (n=10)
Consented to parcipate (n=305)
Randomizaon
Allocated to Pre-operave rectally administrated misoprostol
Allocated to post-operave rectally administrated misoprostol
Lost to flow-up
Lost to flow-up (n=3)
(n=2)
Analyzed (n=150)
Figure 1
Table 1
Analyzed (n=150)
Flow chart of the study design.
Patients characteristics of the study groups.
Age (years) Parity Body mass index Gestational age Preoperative Hb level
Study group (N = 150)
Control group (N = 150)
p value
24.7 ± 4 3.20 ± 1.1 21 ± 0.8 39.4 ± 0.8 11.8 ± 3.6
25.08 ± 3.9 3.5 ± 1.9 22 ± 0.6 39.1 ± 0.9 11.6 ± 4.8
0.542 0.461 0.442 0.58 0.48
Values presented by mean ± SD, p value < 0.05 was set be significant.
section. Reduction of operative blood loss at cesarean section is beneficial to patients in terms of decreased postoperative morbidity and a decrease in risks associated with blood transfusions (6). Misoprostol, a PGE1 analogue, has been investigated both for prevention and management of PPH due to its uterotonic effect. However, there is no general consensus on the optimal time, dose or route of administration (7). Rectally administered misoprostol has the advantage of a slower absorption rate, lower concentration level and consequently lower adverse effects (8) compared to Sublingual misoprostol, which has the greatest bioavailability among all routes of administration and a higher incidence of complications (6). On the other hand, oral route has the highest side effects (8,9). For these reasons, the rectal route was the preferred route of administration in the present study. The current study used 600 lg of misoprostol which was administered rectally in
both groups after catheter insertion and before draping to allow time for absorption and action to occur. Because we are comparing the optimal time for misoprostol administration, other uterotonic drugs were instituted when intra-operative or post-operative bleeding exceeded 500 ml. In the current study, the mean blood loss during and after CS delivery was significantly lower in the pre-operative rectally administered misoprostol group compared to those receiving misoprostol post-operatively. This can be explained by the fact that, high availability and higher concentration of misoprostol had occurred after the end of the surgical procedure, hence leading to strong uterine contraction and consequently resulted in the reduction of blood lost. Further study is warranted to determine the concentration of misoprostol in the blood in both groups following the end of the procedure. A randomized controlled trial using 400 lg was conducted to evaluate the im-
Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given Table 2
11
Primary outcome measures in the two studied groups.
Characteristics
Study group (n = 150)
Control group (N = 150)
p value
Blood loss ML Need for uterotonic drug No need Need Mean Hb level((g/dl) Postoperative 24 h Change in Hb
620 ± 291
898 ± 321
0.003
105 (70) 45 (30)
70 (46.7) 80 (53.3)
0.023
10.5 ± 1.31 1.2 ± 0.67
9.8 ± 1.24 1.9 ± 0.45
p < 0.05 0.032
Values are presented as (Mean ± SD), number (percentage), p value < 0.05 was set be significant.
Table 3
Fetal and drug adverse effect in both groups.
Apgar score at 5 min Meconium aspiration NICU admission Pyrexia Shivering Vomiting
Study group (N = 100)
Control group (N = 100)
p value
9.74 ± 0.66 8 ± 0.42 7 ± 0.31 15 (15%) 20 (20%) 7 (7%)
9.88 ± 0.60 6 ± 0.56 7 ± 0.42 17 (17%) 18 (18%) 11 (11%)
>0.05 >0.05 >0.05 >0.05 >0.05 >0.05
pact of preoperative administration of rectal misoprostol on blood loss among 400 women undergoing elective cesarean delivery and concluded that, preoperative treatment with 400 lg rectal misoprostol significantly reduced blood loss (10). Most of the relevant studies supported the view that rectally administered misoprostol is better than other uterotonic drugs in reducing blood loss specially if administered rectally (11). In the present study, post-operative Hb level (after 24 h) was significantly lower in the post-operative rectally administered misoprostol (9.8 ± 1.24 g/dl) than pre-operatively administered group (10.5 ± 1.31 g/dl), p < 0.05. This finding agrees with results obtained by Elsedeek who concluded that, pre-operative rectally administered misoprostol after elective CS resulted in a significantly higher Hb level and hematocrit values in rectally administered misoprostol than placebo (10). Pre-operative misoprostol was used via oral (12) and sublingual routes for different operations for blood reduction which was reported to be effective in reducing blood loss during surgery (13). The additional need for other uterotonic drugs to control blood loss during CS delivery was markedly noticed in women who received post-operative misoprostol (n = 80, 53.3%) compared to women who received pre-operative misoprostol (n = 4530%), p < 0.05 respectively. Again, this finding is in agreement with the results of Elseedeek (10) who mention in their studies that the percentage of women requiring additional oxytocics was significantly higher in the control group than in the study group (10). Jennifer et al., 2005, reported the same findings however, in their study they used the buccal route, not the rectal route for drug administration (11). In this study, there was no clinically significant difference in the neonatal outcomes in both groups as regards the timing of administration of the drug and this agrees with the results obtained by Elsedeek (10) who reported that the preoperative administration of the misoprostol rectally did not cause any fetal adverse effects in the study group.
5. Conclusion Pre-operative rectally administrated misoprostol appears to be more effective than post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need for other uterotonic drugs in cesarean section delivery. Conflict of interest We declare no conflict of interest. References (1) Mousa H, Alfirevic Z. Treatment for primary postpartum hemorrhage (Cochrane review). Chichcster (UK): John Wiley & Sons Ltd. The Cochrane Library; 2009, Issue 4. (2) Chong Y, Sull A, Arulkumaran S. Current strategies for the prevention of postpartum hemorrhage in the third stage of labor. Curr Opin Obstet Gynecol 2004;16(2):143–50. (3) Derman R, Kodkany B, Goudar S, Geller S, Naik V, Belied M, et al. Oral misoprostol in preventing postpartum hemorrhage in resource-poor communities: a randomized controlled trail. Lancet 2006;368(9543):124–53. (4) Tang O, Schwer H, Eberth H. Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod 2002;17:332–6. (5) Picklu C, Gita B, Apurba. Rectally administrated misoprostol versus intravenous oxytocin infusion during cesarean delivery to reduce intraoperative and postoperative blood loss. Int J Gynaecol Obstet 2010;109(1 (April)):25–9. http://dx.doi.org/10.1016/ j.ijgo.2009.11.00, Epub 2010 January 13. (6) Lapaire O, Schneider MC, Stotz M, Surbek DV, Holzgreve W, Hoesli IM. Oral misoprostol vs. intravenous oxytocin in reducing blood loss after emergency cesarean delivery.. Int J Gynaecol Obstet 2006;95(1 (October)):2–7, Epub 2006 August 23. (7) El-Refaey H, Rodeck C. Postpartum hemorrhage: definitions, medical and surgical management. A time for change. Br Med Bull 2003;67:205–17.
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