Table 1 Studies Included in Scoping Review
Study & Country | Study type | Intervention (I1) & Control (I2) | Time point of drug application | Population | Follow-up & beginning and end of study | ||||
|---|---|---|---|---|---|---|---|---|---|
Week of gestation (mean ± SD) | Women (n) | Age (mean ± SD; median [range]) | Indication | ||||||
Comparative dose-response studies | Balki 2006 [26] Canada | RCT | “the dose of oxytocin for each patient was determined by the response of the previous patient (±0,5 IU) to the drug, according to a biased coin up- and-down sequential allocation scheme to cluster doses close to the minimum effective dose (ED90)”a | “immediately upon delivery of the anterior shoulder of the infant” | 39.9 ± 1.1 | total: 30 | 32.7 ± 4.4 | CS for labour arrest “augmentation with iv oxytocin for a minimum of 2 h” | 48 h 03/04–12/04 |
Lavoie 2015 [27] US | RCT | “dose-response study using a 9:1 biased-coin sequential allocation method to estimate the ED90 of an infusion of prophylactic oxytocin in women undergoing CS with neuraxial anesthesia. The starting infusion rate was 18 IU/h, with an incremental dose of 2 IU/h.” | “immediately after the umbilical cord was clamped” | I1: 40 (40–41) I2: 39 (39–39) | I1: 32 I2: 38 | I1: 33 (28–35) I2: 33 (31–36) | I1:“labouring group: women scheduled for intrapartum CS after prior exposure to exogenous oxytocin”b I2:“non-labouring group: women scheduled for CS” | 24 h 08/12–06/13 | |
Different Oxytocin doses | Munn 2001 [28] US | RCT | I1: Oxytocin 10 IU, iv, 30 min I2: Oxytocin 80 IU, iv, 30 min +prn Oxytocin for labour induction;c after delivery in the postanesthesia care unit, all patients received oxytocin, 20 IU, iv, 8 h | “after cord clamping” | I1: 37 ± 4.3 I2: 37 ± 4.9 | I1: 163 I2: 158 | I1: 25 ± 6.0 I2: 25 ± 6.1 | labour before CSd | 1 day 01/97–11/99 |
Ayedi 2011 [55] Tunisia | RCT | I1: Oxytocin 2 IU (in 5 ml volume), iv, single-dose, 5–10 s I2: Oxytocin 5 IU (in 5 ml volume), iv, single-dose, 5–10 s +prn uterotonics | “after delivery of the baby and cord clamping” | ≥37 | total: 60 | – | – | – | |
Chou 2015 [56] Malaysia | RCT | I1: Oxytocin 40 IU (in 500 ml NaCl), iv, over 6 h I2: Oxytocin 80 IU (in 500 ml NaCl), iv, over 6 h +all P. were given an oxytocin bolus of 5 IU | “post-delivery” | – | – | – | – | - 11/12–05/13 | |
Khan 2012 [32] India | RCT | I1: Oxytocin 10 IU (in 500 ml NaCl), iv, over 1 h I2: Oxytocin 20 IU (in 500 ml NaCl), iv, over 1 h +prn uterotonics | – | – | total: 200 | – | emergency | 24 h study duration: 6 mos | |
Kintu 2012 [54] Uganda | RCT | I1: Oxytocin 2.5 IU, no further information I2: Oxytocin 10 IU, no further information +prn uterotonics | “following cord clamping” | – | total: 380 | – | emergency and elective | 24 h - | |
Lee 2014 [48] US | Non-RCT (retrospective) | I1: Oxytocin 10 IU, iv Infusion was continued until P. transfer to the recovery room I2: Oxytocin 30 IU, iv, over 1 h | “following cord clamping” | – | I1: 483 I2: 418 | I1: 32 ± 6 I2: 33 ± 6 | – | - I1: 09/08–11/08 I2: 11/08–01/09 | |
Pursche 2012 [42] Germany | Non-RCT (retrospective) | I1: Oxytocin 3 IU, iv, single-dose + continuously 3 IU oxytocin, iv, infusion rate 100 ml/h I2: Oxytocin continuously 3 IU oxytocin, iv, infusion rate at least 120 ml/h | “postpartum” | I1: 37.9 I2: 37.9 | I1: 228 I2: 227 | – | elective (n = 71) and during labour (n = 384)e | 4 h 01/11–12/11 | |
McClune 2011 [44] UK | Non-RCT (retrospective) | Different doses oxytocin, not administered uniformlyf + prn uterotonics | “given at cord clamping” | – | total: 50 | – | – | - 08/10–09/10 | |
Application schema | Mangla 2012 [59] India | RCT | I1: Oxytocin 20 IU, iv I2: Oxytocin 5 IU, imy I3: Oxytocin 5 IU, imy No information about additional uterotonics | I1 + I2: “after separation of placenta” I3: “before separation of placenta” | – | I1: 50 I2: 50 I3: 50 | – | – | 1 h - |
Oxytocin vs other uterotonics time-dependent | Adefuye 2012 [50] Nigeria | RCT | I1: Oxytocin 20 IU, iv I2: Misoprostol 2 × 400 μg, sublingual +prn uterotonics intraop | I1: “after delivery” I2: “before delivery” | I1: 38.0 ± 0.2 I2: 38.1 ± 0.3 | I1: 50 I2: 50 | I1: 28.7 ± 0.7 I2: 29.9 ± 0.8 | elective (28%) and emergency (72%)g | 24 h 04/09–03/11 |
Chaudhuri 2010 [60] India | RCT | I1: Oxytocin 8 × 5 IU, iv + placebo, rectal I2: Misoprostol 4 × 200 μg, rectal + 8 placebo, iv +prn uterotonics | I1: “after delivery” I2: “before incision” | I1: 39.2 ± 1.4 I2: 39.5 ± 1.7 | I1: 100 I2: 100 | I1: 24.3 ± 5.0 I2: 24.0 ± 3.4 | elective and emergencyh without risk factors for PPH | 24 h 12/07–06/09 | |
Oxytocin vs placebo | King 2010 [49] Canada | RCT | I1: Oxytocin 5 IU, iv, über 30 s, single-dose I2: Placebo NaCl, iv, 30 s, single-dose +routinely oxytocin (40 IU, iv, 30 min) followed by oxytocin (20 IU) immediately after study drug +prn uterotonics | “as soon as the umbilical cord was clamped” | I1: 37.0 ± 3.0 I2: 38.0 ± 2.0 | I1: 75 I2: 75 | I1: 34 ± 5 I2: 34 ± 6 | elective (n = 76) and non-elective (n = 67) at least one risk factor for PPH | 24 h 11/05–10/06 |
Oxytocin vs other uterotonics | Attilakos 2010 [34] UK | RCT | I1: Oxytocin 5 IU, iv, 30–60 s I2: Carbetocin 100 μg, iv, 30–60 s +prn uterotonics (Oxytocin for PPH prophylaxis or treatment) | “after the birth of the baby” | ≥37 | I1: 189 I2: 188 | I1: 32 (18–44) I2: 32 (18–42) | elective (60%) and emergency (40%) 1/3 showed risk factors for PPH | until discharged 11/06–07/07 |
Borruto 2009 [35] Italy | RCT | I1: Oxytocin 10 IU, iv, 2 h I2: Carbetocin 100 μg, iv, single-dose +prn uterotonics | “immediately following placental delivery” | ≥36 | I1: 52 I2: 52 | 32.2 (22–41) | planned and emergencyi at least one risk factor for PPH | 24 h 09/07–01/08 | |
Catanzarite 1990 [47] US | RCT | I1: Oxytocin 20 IU, imy I2: Carboprost tromethamine 125 μg, imy +routinely oxytocin (20 IU, iv) after placental delivery | “immediately following placental delivery” | – | I1: 21 I2: 25 | I1: 24.5 I2: 24.1 | planned and emergencyj | 3 days - | |
Chaudhuri 2014 [33] India | RCT | I1: Oxytocin 8 × 5 IU, iv, 12 h + placebo rectal I2: Misoprostol 4 × 200 μg, rectal + placebo iv, 12 h +routinely oxytocin, not later than 1 min after delivery | “at the end of the operation” | I1: 38.8 ± 1.2 I2: 39.0 ± 1.1 | I1: 96 I2: 96 | I1: 23.2 ± 3.7 I2: 23.5 ± 4.5 | emergency without risk factor for PPH | 24 h 05/11–05/12 | |
Lapaire 2006 [36] Switzerland | RCT | I1: Oxytocin 20 IU, iv, 8 h + placebo oral I2: Misoprostol 800 μg, oral + placebo iv, 8 h +routinely oxytocin (5 IU, iv) after cord clamping | “immediately after cord clamping” | I1: 38.7 ± 1.3 I2: 38.6 ± 1.3 | I1: 28 I2: 28 | I1: 31.2 ± 5.1 I2: 32.2 ± 6.5 | elective and indicatedk low risk for PPH | 48 h 01/99–02/02 | |
Lokugamage 2001 [37] UK | RCT | I1: Oxytocin 10 IU, iv, single-dose + placebo, oral I2: Misoprostol 500 μg, oral + placebo iv, single-dose +prn uterotonics | “immediately after the delivery of the baby” | I1: 38.3 ± 1.1 I2: 36.7 ± 8.9 | I1: 20 I2: 20 | I1: 31.4 ± 5.5 I2: 32.3 ± 6.4 | elective (n = 38) and emergency (n = 2) excluded: previous rupture of the uterus | 3 days - | |
Owonikoko 2011 [51] Nigeria | RCT | I1: Oxytocin 20 IU, iv I2: Misoprostol 400 μg, sublingual +prn Oxytocin iv | “immediately after extraction of the baby” | I1: 39.7 ± 1.9 I2: 38.7 ± 2.3 | I1: 50 I2: 50 | I1: 30.4 ± 4.8 I2: 31.5 ± 4.1 | elective (35%)l and emergency (65%)m | 24 h 06/06–04/07 | |
Razali 2016 [30] Malaysia | RCT | I1: Oxytocin 10 IU, iv, single-dose I2: Carbetocin 100 μg, iv, single-dose +prn uterotonics | “after delivery” | “at term” | I1: 300 I2: 300 | I1: 29.7 ± 4.3 I2: 29.5 ± 4.6 | emergencyn | 24 h 14/08–09/12 | |
Vimala 2006 [61] India | RCT | I1: Oxytocin 20 IU, iv, 6 h I2: Mis +prn uterotonics | “immediatiely after delivery of the neonate” | I1: 38.7 ± 1.1 I2: 38.7 ± 1.2 | I1: 50 I2: 50 | I1: 26.3 ± 3.7 I2: 25.6 ± 5.1 | elective (17%) and emergency (83%)o without risk factors for PPH | 24 h 08/04–04/05 | |
El Behery 2016 [29] Egypt | RCT | I1: Oxytocin 20 IU, iv I2: Carbetocin 100 μg, iv, 2 min +prn uterotonics | “after delivery of the infant preferably before placental removal” | I1: 38.2 ± 0.8 I2: 38.2 ± 1.2 | I1: 90 I2: 90 | I1: n = 90 I2: n = 90 | emergency | 24 h 01/13–06/14 | |
Whigham 2016 [31] Australia | RCT | I1: Oxytocin 5 IU, iv I2: Carbetocin 100 μg, iv +prn uterotonics | “immediately after birth of the baby” | I1: 40.0 ± 1.4 I2: 39.6 ± 1.5 | I1: 53 I2: 59 | I1: 28.9 ± 5.8 I2: 28.3 ± 5.9 | non-elective and emergencyp | - 08/12–02/13 | |
Alli 2013 [53] Nigeria | RCT | I1: Oxytocin 10 IU, iv, single-dose I2: Misoprostol 600 μg, sublingual +prn uterotonics | “immediately after delivery of the baby” | – | total: 100 | – | – | – | |
Begum 2015 [57] Bangladesh | RCT | I1: Oxytocin 20 IU (in 100 ml Dextrose NaCl), iv I2: Misoprostol 400 μg, sublingual +prn uterotonics | “soon after delivery” | “term pregnancy” | total: 100 | – | – | – | |
Pizzagalli 2015 [41] France | Non-RCT (prospective) | I1: Oxytocin 5 IU iv, followed by 10 IU iv during surgery, further infusions 10 IU 8 h postop I2: Carbetocin 100 μg iv I3: Oxytocin 5 IU iv, followed by 10 IU iv during surgery, further infusions 10 IU 8 h + Sulprostone | “during cord clamping” | ≥37 | I1: 282 I2: 262 I3: 258 | – | CS before labour (n = 283) and unclear indication (n = 519) | 24 h I1: 07/10–12/10 I2: 02/11–12/11 I3: 08/11–01/12 | |
Triopon 2010 [62] France | Non-RCT (retrospective) | I1: Carbetocin 100 μg, iv I2: Oxytocin 5 IU, iv | “after cord clamping” | I1: 38.2 ± 3.0 I2: 37.9 ± 3.2 | I1: 155 I2: 155 | I1: 30.6 ± 5.3 I2: 30.7 ± 5.4 | elective and during labour | 24 h I1: 04/09–07/09 I2: 03/07–06/07 | |
Demetz 2013 [46] France | Non-RCT (retrospective) | I1: Oxytocin 10 IU, iv, single-doseq +3 h after delivery: 10 IU Oxytocin iv over 12 h I2: Carbetocin 100 μg, iv, single-dose +3 h after delivery: 10 IU Oxytocin iv over 12 h | “at the delivery” | I1: 35.5 ± 2.5 I2: 34.3 ± 3.1 | I1: 24 I2: 39 | I1: 31.6 ± 4.3 I2: 31.1 ± 5.8 | planned (n = 31) and unclear (n = 32) | 48 h I1: 08/09–01/10 I2: 02/10–07/10 | |
Testa 2013 [45] Italy | Non-RCT (retrospective) | I1: Oxytocin 10 IU, iv, 2 h I2: Carbetocin 100 μg, iv, single-dose | – | – | I1: 14 I2: 14 | – | planned and emergency | 24 h after drug application - | |
Brzozowska 2015 [63] Polska | Non-RCT (retrospective) | I1: Oxytocin 10 IU, im I2: Carbetocin 100 μg, iv +prn uterotonics | – | I1: 38.3 ± 1.9 I2: 38.1 ± 1.9 | I1: 140 I2: 139 | I1: 30.5 ± 4.6 I2: 31.5 ± 5.1 | – | - 03/14–10/14 | |
Combination therapy | Koen 2016 [52] South Africa | RCT | I1: Oxytocin 2,5 IU, iv, single-dose + placebo im I2: Oxytocin + Ergometrine Placebo iv + Oxytocin 5 IU, im + Ergometrine 0.5 mg, im +routinely 10 IU Oxytocin | “after delivery of the neonate” | I1: 38.4 ± 2.2 I2: 38.5 ± 1.9 | I1: 214 I2: 202 | I1: 28.6 ± 6.0 I2: 28.9 ± 5.4 | elective (36%) and emergency (64%)r | 6–24 h 01/4–06/14 |
Mahmud 2014 [58] Pakistan | Non-RCT (prospective) | I1: Oxytocin 10 IU iv I2: Oxytocin 10 IU iv + Ergometrine 0,25 mg im | “intraoperatively” | I1: 37.5 ± 2.0 I2: 38.0 ± 1.8 | I1: 378 I2: 323 | I1: 28.0 ± 3.5 I2: 29.0 ± 3.4 | elective and emergency | 6 h I1: 11/10–12/10 I2: 01/11–02/11 | |
Bayoumeu 2003 [38] France | Non-RCT (retrospective) | I1: Oxytocin 5 IU iv (single dose), 10 IU iv 30 min, afterwards 25 IU iv 24 h I2: Oxytocin 5 IU iv (single dose), 10 IU iv 30 min, afterwards 25 IU iv 24 h + Dinoprost/Sulprostone | “after clamping the last umbilical cord” | I1: 32.0 ± 2.7 I2: 32.8 ± 1.7 | I1: 14 I2: 28 | I1: 29.1 ± 3.2 I2: 30.2 ± 3.3 | elective and emergency | 48 h I1: 01/93–11/96 I2: 12/96–12/00 | |
Lourens 2007 [40] UK | Non-RCT (prospective) | I1: Oxytocin 5 IU iv, single-dose I2: Oxytocin 5 IU iv, single-dose + Ergometrine 0.5 mg im | Oxytocin: “after delivery” Ergometrine: “during abdominal closure” | I1: 38.0 ± 1.0 I2: 38.0 ± 1.0 | I1: 158 I2: 107 | – | elective (n = 120) and emergency (n = 145) | - I1: 02/06–03/06 I2: 04/06–06/06 | |