Dosering van oxytocine ter preventie van HPP
Uitgangsvraag
Wat is de meest aangewezen strategie (of beleid) bij intraveneuze (i.v.) toediening van oxytocine ter preventie van HPP?
Aanbeveling
Kies bij vrouwen die een sectio caesarea ondergaan voor de profylactische dosering oxytocine van 3 IU iv in 5 minuten als bolus, gevolgd door een onderhoudsdosering van 2,5 IU per uur gedurende 4 uur.
Kies bij vrouwen die vaginaal bevallen met een verhoogd risico op HPP voor de profylactische dosering oxytocine van 3 IU iv in 5 minuten als bolus, gevolgd door een onderhoudsdosering van 2.5 IU per uur gedurende 4 uur.
Geef bij klinisch barende vrouwen met een laag risico op HPP, indien gekozen wordt voor profylaxe, een eenmalige dosering van 5 IE iv in 5 minuten (zonder onderhoudsdosering) of 10 IE im indien geen intraveneuze toegang aanwezig is.
Voor de identificatie van risicofactoren voor HPP en de behandeling van HPP wordt verwezen naar de Fluxus Implementatie Strategie en naar het modelprotocol behandeling van HPP.
Overwegingen
Voor- en nadelen van de interventie en de kwaliteit van het bewijs
De werkgroep heeft een literatuurstudie verricht om te achterhalen wat de meest aangewezen oplaaddosis oxytocine is ter preventie van HPP, waarbij de minste bijwerkingen te verwachten zijn. In totaal werden er vijf studies geïncludeerd, waarbij alleen vrouwen met een electieve sectio caesarea werden geincludeerd. (Butwick, 2010; Kim, 2011; Kothari, 2018; McDonagh, 2022; Sartain, 2008). Dit maakt een generalisatie naar vrouwen met een secundaire sectio of een al dan niet gecompliceerde vaginale baring niet goed mogelijk.
0.5 IU versus 5 IU oxytocine
Twee studies onderzochten het effect van een oplaaddosis van 0.5 IU oxytocine vergeleken met 5 IU oxytocine (Butwick, 2010; McDonagh, 2022). De bewijskracht voor de cruciale uitkomstmaat ‘bloedverlies >1000 mL’ was laag vanwege spreiding in de richting van het effect. In de studie van Mc Donagh werd bij 0.5 IU oxytocine minder vaak ernstige bloedverlies (>1000 mL) beschreven in vergelijking met 5 IU oxytocine. In beide groepen werd een onderhoudsdosering van 2.4 IU per uur gegeven wat mogelijk de resultaten beïnvloedde. Voor de cruciale uitkomstmaten shock, maternale sterfte en bloedtransfusie werd geen bewijs gevonden. Echter leek 0.5 IU oxytocine het gebruik van aanvullende uterotonica te verhogen vergeleken met 5 IU oxytocine. Over het algemeen werd er geen verschil gezien in de bijwerkingen tussen 0.5 IU en 5 IU oxytocine, maar 0.5 IU oxytocine resulteerde mogelijk in minder misselijkheid vergeleken met 5 IU oxytocine.
1 IU versus 5 IU oxytocine
Eén studie onderzocht het effect van 1 IU oxytocine vergeleken met 5 IU oxytocine (Butwick, 2010). Voor de cruciale uitkomstmaten bloedverlies >1000 mL, shock, maternale sterfte en bloedtransfusie werd geen bewijs gevonden. Echter leek 1 IU oxytocine te resulteren in minder hypotensie ten opzichte van 5 IU oxytocine.
2 IU versus 5 IU oxytocine
Twee studies onderzochten het effect van 2 IU oxytocine vergeleken met 5 IU oxytocine (Kim, 2011; Sartain, 2008). Voor de cruciale uitkomstmaten bloedverlies >1000 mL, shock, maternale sterfte en bloedtransfusie werd geen bewijs gevonden. Echter leek 2 IU oxytocine te resulteren in minder misselijkheid vergeleken met 5 IU oxytocine.
3 IU versus 5 IU oxytocine
Twee studies onderzochten het effect van 3 IU oxytocine vergeleken met 5 IU oxytocine (Butwick, 2010; Kothari, 2018). Voor de cruciale uitkomstmaten bloedverlies >1000 mL, shock, maternale sterfte en bloedtransfusie werd geen bewijs gevonden. Echter leek 3 IU oxytocine te resulteren in minder hypotensie vergeleken met 5 IU oxytocine.
3 IU versus 10 IU oxytocine
Eén studie onderzocht het effect van 3 IU oxytocine vergeleken met 10 IU oxytocine (Kothari, 2018). Voor de cruciale uitkomstmaten bloedverlies >1000 mL, shock, maternale sterfte en bloedtransfusie werd geen bewijs gevonden. Echter leek 3 IU oxytocine te resulteren in minder hypotensie, misselijkheid/overgeven en pijn op de borst dan 10 IU oxytocine.
Vanwege de methode, waarbij in de huidige PICO vorm 2 interventies worden vergeleken, waarna een gerichte literatuursearch vorm uitgevoerd wordt, worden netwerk meta- analyses niet geïncludeerd. Hierdoor wordt een belangrijk artikel van Tantry uit 2023 niet opgenomen terwijl deze waarschijnlijk wel een beter antwoord kan geven omdat juist veel verschillende combinaties van oxytocine dosering in zowel bolus, infusie gedurende langere tijd of combinaties hiervan mogelijk zijn.
In een systematische review met netwerk meta-analyse van cluster based groups van Tantry et al werden verschillende behandelstrategieën met een bolus, onderhoudsdosering of combinaties vergeleken met als belangrijkste uitkomstmaat de noodzaak van additionele uterotonica en de hoeveelheid bloedverlies maar ook bijwerkingen bij vrouwen na een electieve sectio. De bolusdosering werd gecategoriseerd in < 3, 3-5 en > 5 IU oxytocine in een periode van minder dan 10 minuten. De infusiedosering werd gecategoriseerd in < 0.25, 0.25-1.0 of > 1 IU oxytocine per minuut en bedroegen periodes langer dan 10 min. In totaal werden 33 RCT’s met 6721 vrouwen geïncludeerd. Er werden 14 verschillende combinaties van bolus en infusie vergeleken. Er werd geconcludeerd dat de combinatie van een bolus van 3-5 IU gevolgd door een infusie van 0.25-1.0 IU/min het meest optimale effect gaf. Hogere doses gaven meer bijwerkingen. De duur van de onderhoudsdosering verschilde, betrof wel vaak meerdere uren. Er werd door de auteurs geen advies over de onderhoudsdosering gegeven.
De individuele studies uit onze literatuurstudie suggereren dat een lagere dosis dan de tot nu toe gebruikte 5 IU niet tot meer bloedverlies leidt, met minder bijwerkingen maar bij een aantal van deze studies werd de initiële bolus van 0.5-3 IU wel gevolgd door een onderhoudsdosis. Er zou dus overwogen kunnen worden wel de laagere dosis (3 IU) te gebruiken, gevolgd door een onderhoudsdosering.
De studies die voor deze PICO gebruikt konden worden betreffen vrouwen na een electieve sectio, wat de generaliseerbaarheid naar vrouwen met een vaginale baring of secundaire sectio waarbij eerder oxytocine als bijstimulatie gebruikt is lastig maakt.
Op basis van studies naar effectiviteit van oxytocine bij diverse patiëntengroepen bij sectio caesarea (primaire SC, secundaire SC, SC bij obesitas) kan geconcludeerd worden dat minder dan 5 IU als oplaaddosis afdoende is. De ED90 (effectieve dosis om een adequate contractie te bewerkstelligen) bij een electieve SC is 0.35 IE (Carvalho Obst & Gyn 2004), de ED 90 bij obesitas is 0.75 IE (Peska Anaesthesia 2021), de ED 90 bij een secundaire SC is 2.99 IE (Balki Obst&Gyn 2006).
Waarden en voorkeuren van patiënten (en evt. hun verzorgers)
Deze uitgangsvraag gaat niet over of er wel of geen profylaxe gegeven dient te worden, maar over de dosering. Als er aan de hand van de principes van Samen Beslissen samen met de cliënt voor wordt gekozen om profylaxe te geven ter preventie van hevig bloedverlies, is het voor de vrouw belangrijk een middel toegediend te krijgen dat zo effectief mogelijk is en zo min mogelijk bijwerkingen met zich meebrengt. Hierbij moeten vrouwen altijd een individuele afweging kunnen maken tussen de mate van/kans op preventie en de bijwerkingen die zij mogelijk zullen ervaren in het belangrijke eerste levensuur, het gouden uur. Het is belangrijk voor de vrouw (en haar partner) dat er in een gesprek ruim voor de bevalling over de mogelijke preventie van HPP door toediening van profylaxe wordt gesproken, zodat de cliënt een goede afweging kan maken. Bij een eventuele onderhoudsdosis is het van belang dat ook deze in afstemming met de vrouw wordt besproken en (her)bevestigd.
Kosten (middelenbeslag)
Oxytocine is een goedkoop middel. Het effect op kosten zal met name liggen in het effect en het al dan niet noodzakelijk zijn van aanvullende maatregelen en niet in de kosten die een hoge of lage dosis met zich meebrengen.
Aanvaardbaarheid, haalbaarheid en implementatie
De richtlijn uit 2018 adviseerde een bolus oxytocine van 5IU, gevolgd door een onderhoudsdosering van 2.5 IU per uur gedurende 4 uur bij mensen met een verhoogd risico op HPP. Dit betrof zowel vaginale baringen als sectio’s waarbij een sectio op zichzelf als hoog risico werd gezien.
Op basis van de studies naar de dosis die een effectieve contractie van de uterus verkrijgt zou ervoor gekozen kunnen worden om bij verschillende situaties aangepaste doseringen van de initiële bolus toe te passen, variërend van 1 tot 3 IU. De bewijskracht van het effect op het bloedverlies en de praktische toepasbaarheid maakt echter dat een meer generiek protocol mogelijk te verkiezen is. De netwerkanalyse geeft een voorkeur voor 3-5 IU als initiële bolus.
De werkgroep is van mening dat de initiële bolus kan worden teruggebracht naar 3IU, gegeven in een periode van 5 minuten indien er een onderhoudsdosering volgt. Hoewel de generaliseerbaarheid naar vaginale bevallingen bediscussieerd kan worden, wordt ervoor gekozen om voor vrouwen na een keizersnede en een vaginale bevalling met een verhoogd risico op HPP het advies eenduidig te maken om de kans op fouten te verkleinen.
De meeste studies geven na een initiële bolus een onderhoudsdosering. Dit betreft wederom studies naar vrouwen met een sectio caesarea. De netwerkanalyse geeft een advies om 15 IU per uur te geven. Dit zou betekenen dat een zeer forse verhoging van de dosering nodig zou zijn. De werkgroep is van mening dat dit ten opzichte van de huidige situatie een onwenselijke stijging zou betekenen en adviseert de huidige dosering te handhaven maar dit wel als kennislacune te duiden.
Voor vrouwen met een laag risico op HPP kan op basis van de huidige literatuursearch geen goed antwoord gegeven worden. Er kan geen uitspraak gedaan worden van het effect van het verlagen van dosering van de bolus indien geen additionele onderhoudsdosering wordt gegeven. Er is dan ook te weinig bewijs om het huidige beleid aan te passen voor deze vrouwen en volledigheidshalve wordt deze in de aanbeveling opgenomen.
Onderbouwing
Achtergrond
Prophylactic oxytocin is used to prevent postpartum haemorrhage (HPP). The NVOG guideline of 2018 advises a dosage of 5 IU bolus in all women, followed by an infusion of 2.5 IU per hour in the course of 4 hours in women with a high risk of HPP, including primary and secondary caesarean section. Oxytocin, especially a rapidly given bolus dose, can lead to nausea, vomiting and cardiovascular side effects like hypotension, tachycardia and ischemia and studies suggest a lower bolus dose to have less side effects. Therefore the question is what the optimal strategy of oxytocin is to prevent HPP with the least side effects.
Conclusies / Summary of Findings
Comparison 0.5 IU versus 5 IU
|
Low GRADE |
The evidence suggests that initial dose of 0.5 units of oxytocin reduces blood loss >1000 mL when compared with 5 units in women postpartum during caesarean section. However, in both groups a continuous infusion of 2.4 IU was given.
Source: McDonagh, 2022 |
|
Very low GRADE |
The evidence is very uncertain about the effect of 0.5 units of oxytocin on blood loss when compared with 5 units of oxytocin in women postpartum during and caesarean section.
Source: Butwick, 2010; McDonagh, 2022 |
|
Low GRADE |
The evidence suggests that an initial dose of 0.5 units of oxytocin increases the use of additional uterotonics when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: McDonagh, 2022 |
|
Moderate GRADE |
Initial dose of 0.5 units of oxytocin probably results in little to no difference in adverse effects when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: McDonagh, 2022 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 0.5 units of oxytocin on hypotension when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; McDonagh, 2022 |
|
Low GRADE |
The evidence suggests that an initial dose of 0.5 units of oxytocin results in little nausea when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; McDonagh, 2022 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 0.5 units of oxytocin on vomiting when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; McDonagh, 2022 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 0.5 units of oxytocin on chest pain when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; McDonagh, 2022 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 0.5 units of oxytocin on irregular heart beat when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; McDonagh, 2022 |
|
NO GRADE |
No evidence was found regarding the effect of an initial dose of 0.5 units of oxytocin on shock, maternal death, blood transfusion, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and PTSD when compared with 5 units of oxytocin in women postpartum during caesarean section. |
Comparison 1 IU versus 5 IU
|
Low GRADE |
The evidence suggests that an initial dose of 1 unit of oxytocin results in little to no difference in blood loss when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
Low GRADE |
The evidence suggests that an initial dose of 1 unit of oxytocin results in little to no difference in use of additional uterotonics when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
Low GRADE |
The evidence suggests that an initial dose of 1 unit of oxytocin results in a reduction of hypotension when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
Low GRADE |
The evidence suggests that an initial dose of 1 unit of oxytocin results in little to no difference in nausea when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 1 unit of oxytocin on vomiting when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 1 unit of oxytocin on chest pain when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 1 unit of oxytocin on irregular heart beat when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
NO GRADE |
No evidence was found regarding the effect of an initial dose of 1 unit of oxytocin on blood loss >1000 mL, shock, maternal death, blood transfusion, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and PTSD when compared with 5 units of oxytocin in women postpartum during caesarean section. |
Comparison 2 IU versus 5 IU oxytocin
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 2 units of oxytocin on blood loss when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Kim, 2011 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 2 units of oxytocin on use of additional uterotonics when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Kim, 2011; Sartain, 2008 |
|
Low GRADE |
The evidence suggests that an initial dose of 2 units of oxytocin results in less nausea when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Kim, 2011; Sartain, 2008 |
|
Very low GRADE |
The evidence suggests that an initial dose of 2 units of oxytocin results in less vomiting when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Kim, 2011; Sartain, 2008 |
|
NO GRADE |
No evidence was found regarding the effect of an initial dose of 2 units of oxytocin on shock, maternal death, blood transfusion, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, hypotension, chest pain, irregular heart beat and PTSD when compared with 5 units of oxytocin in women postpartum during caesarean section. |
Comparison 3 IU versus 5 IU
|
Low GRADE |
The evidence suggests that an initial dose of 3 units of oxytocin results in little to no difference in blood loss when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; Kothari, 2018 |
|
Low GRADE |
The evidence suggests that an initial dose of 3 units of oxytocin results in less hypotension when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; Kothari, 2018 |
|
Low GRADE |
The evidence suggests that an initial dose of 3 units of oxytocin results in little to no difference in nausea when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; Kothari, 2018 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 3 units of oxytocin on vomiting when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; Kothari, 2018 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 3 units of oxytocin on chest pain when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010; Kothari, 2018 |
|
Very low GRADE |
The evidence is very uncertain about the effect of an initial dose of 3 units of oxytocin on irregular heart beat when compared with 5 units of oxytocin in women postpartum during caesarean section.
Source: Butwick, 2010 |
|
NO GRADE |
No evidence was found regarding the effect of an initial dose of 3 units of oxytocin on blood loss >1000 mL, shock, maternal death, blood transfusion, use of additional uterotonics, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and PTSD when compared with 5 units of oxytocin in women postpartum during caesarean section. |
Comparison 3 IU versus 10 IU
|
Low GRADE |
The evidence suggests that an initial dose of 3 units of oxytocin results in little to no difference in blood loss when compared with 10 units of oxytocin in women postpartum during caesarean section.
Source: Kothari, 2018 |
|
Low GRADE |
The evidence suggests that an initial dose of an initial dose of 3 units of oxytocin results in less hypotension when compared with 10 units of oxytocin in women postpartum during caesarean section.
Source: Kothari, 2018 |
|
Low GRADE |
The evidence suggests that an initial dose of 3 units of oxytocin results in less nausea/vomiting when compared with 10 units of oxytocin in women postpartum during caesarean section.
Source: Kothari, 2018 |
|
Low GRADE |
The evidence suggests that an initial dose of 3 units of oxytocin results in less chest pain when compared with 10 units of oxytocin in women postpartum during caesarean section.
Source: Kothari, 2018 |
|
NO GRADE |
No evidence was found regarding the effect of an initial dose of 3 units of oxytocin on blood loss >1000 mL, shock, maternal death, blood transfusion, use of additional uterotonics, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, irregular heart beat and PTSD when compared with 5 units of oxytocin in women postpartum during caesarean section. |
Samenvatting literatuur
Description of studies
Butwick (2010) performed a double-blind randomized controlled trial to assess the lowest effective bolus dose of oxytocin during elective caesarean delivery. Women between 18 and 40 years old with a singleton pregnancy of ³37 weeks who received elective caesarean delivery with a Pfannenstiel incision and had ASA I or II were included. Exclusion criteria were active labor, ruptured membranes, known drug allergy to oxytocin, multiple gestation, significant obstetric disease (including pregnancy-induced hypertension or pre-eclampsia), known risk factors for postpartum haemorrhage (including abnormal placentation, multiple gestation, uterine fibroids, history of postpartum haemorrhage or uterine atony, and
previous classical uterine incision), inherited or acquired coagulation disorder, and thrombocytopenia (platelet count <100x109). Fifteen women received 0.5 unit oxytocin, 14 women received 1.0 unit oxytocin, 15 women received 3.0 units oxytocin and 15 women received 5.0 units oxytocin. Groups were comparable at baseline. Outcomes of interest were blood loss, additional uterotonics and adverse events.
Kim (2011) performed a randomized controlled trial to assess the lowest effective dose of oxytocin during spinal anesthesia for elective cesarean delivery. Women with a gestational age of 38 weeks or more who were supposed to undergo planned cesarean section under spinal anesthesia and who were classified as Class 1 or 2 according to the American Society of Anesthesiologist (ASA) physical status classification were included. Exclusion criteria were contraindications for spinal anesthesia, a weight of 100 kg or higher, fetal abnormalities, diabetes, gestational hypertension, cardiovascular disease, or cerebral haemorrhage, and women whose labor pain had already started. In total, 20 women received 2 IU bolus-continuous oxytocin injection and 20 women received 5 IU bolus-continuous oxytocin injection. Groups were comparable at baseline. Outcomes of interest were blood loss, additional uterotonics and adverse events.
Kothari (2018) performed a double-blind randomized controlled trial to assess effects of three doses of oxytocin (3, 5 and 10 IU) in elective caesarean delivery under spinal anaesthesia. Pregnant women between 18 and 35 years with singleton pregnancies who had ASA grade I or II and who received elective Lower Segment Caesarean Section were included. Exclusion criteria were active labor, ruptured membranes, known drug allergy to oxytocin, multiple gestations, pregnancy-induced hypertension/ preeclampsia, high-risk cases for postpartum haemorrhage, inherited or acquired coagulation disorder and thrombocytopenia (platelet count <100x109) and significant cardiorespiratory diseases. In total, 50 women received 3 IU oxytocin, 50 women received 5 IU oxytocin and 50 women received 10 IU oxytocin. Groups were comparable at baseline. Outcomes of interest were blood loss and adverse events.
McDonagh (2022) performed a double-blind randomized controlled trial to assess the effects of low- versus high-dose oxytocin at elective caesarean delivery. Pregnant women with a gestational age between 37+0 to 40+6 weeks who underwent elective caesarean delivery under spinal anesthesia were included. Exclusion criteria were an allergy or hypersensitivity to oxytocin or carbetocin, active labor, requirement for general anesthesia, BMI ≥40 kg/m2, and conditions predisposing to uterine atony and postpartum haemorrhage (such as placenta previa, multiple gestation, (pre-)eclampsia, macrosomia, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum haemorrhage, bleeding diathesis, and hepatic, renal or cardiovascular disease). Besides, women who refused to give written informed consent were excluded. In total, 69 women received low-dose oxytocin (0.5 IU bolus + infusion of 40 mIU/min) and 69 women received high-dose oxytocin (5 IU bolus + infusion of 40 mIU/min). Both groups received 20 IU oxytocin in 1 l Ringer’s
lactate solution at a rate of 120 ml/h (40 mIU/min, being 2.4 IU/h). Groups were probably comparable at baseline. Outcomes of interest were use of additional uterotonics, blood loss, and adverse events.
Sartain (2008) performed a randomized double-blind trial to assess hemodynamic and adverse effects of either 2 IU or 5 IU bolus of oxytocin. Women undergoing elective caesarean delivery under regional anesthesia who received either 2 or 5 IU of intravenous oxytocin after delivery were included. Exclusion criteria were women with an increased risk of uterine atony or excessive bleeding (more than two previous caesarean sections, a history of previous postpartum haemorrhage, known placenta previa or accreta, twin pregnancy, and polyhydramnios) or cardiovascular instability (pre-eclampsia or essential hypertension). In total, 40 women received a bolus of 2 units of oxytocin intravenously and 40 women received a bolus of 5 units of oxytocin intravenously. Both groups received a separate infusion of oxytocin 40 units in 1 liter of Hartmann’s solution at 250 ml/h (i.e., 10 units/h for 4 hours). Groups were comparable at baseline. Outcomes of interest were blood loss, use of additional uterotonics and adverse events.
Table 1. Description of included studies.
|
Study |
Intervention |
Comparator |
Outcomes |
||
|
|
Characteristics |
Intervention type/ dose |
Characteristics |
Type of control |
|
|
Butwick, 2010 |
Arm 1a (n=15) Mean age (range): 33 (31–34)
Arm 1b (n=14) Mean age (range): 35.5 (32–38)
Arm 1c (n=15) Mean age (range): 33 (30–36)
|
Oxytocin 0.5 IU
Oxytocin 1 IU
Oxytocin 3 IU |
Arm 2 (n=15) Mean age (range): 32 (29–33) |
Oxytocin 5 U |
Blood loss, additional uterotonics, adverse effects |
|
Kim, 2011 |
Arm 1 (n=20) Mean age (SD): 31.1 (3.1) |
Oxytocin 2 IU |
Arm 2 (n=20) Mean age (SD): 31.1 (2.8) |
Oxytocin 5 IU
|
Blood loss, additional uterotonics, adverse effects |
|
Kothari, 2018 |
Arm 1 (n=50) Mean age (SD): 25.56 (2.72) |
Oxytocin 3 IU
|
Arm 2a (n=50) Mean age (SD): 25.06 (2.96)
Arm 2b (n=50) Mean age (SD): 24.62 (2.67)
|
Oxytocin 5 IU
Oxytocin 10 IU |
Blood loss, adverse effects |
|
McDonagh, 2022 |
Arm 1 (n=69) Mean age (SD): 34.8 (4.0) |
Oxytocin 0.5 IU |
Arm 2 (n=69) Mean age (SD): 35.1 (4.0) |
Oxytocin 5 IU |
Blood loss (>1000mL), additional uterotonics, adverse effects |
|
Sartain, 2008 |
Arm 1 (n=40) Mean age (range): 30.8 (20–40)
|
Oxytocin 2 IU |
Arm 2 (n=40) Mean age (range): 30.9 (21–41)
|
Oxytocin 5 U |
Blood loss, additional uterotonics, adverse effects |
All studies concern caesarean sections.
Results
Comparison 0.5 IU versus 5 IU
1. Blood loss > 1000 mL (critical)
McDonagh (2022) reported that 23 of the 68 women (34%) who received 0.5 units of oxytocin had a blood loss ³1000 mL as compared to 26 of the 67 women (39%) who received 5 units of oxytocin (RR=0.87, 95%CI 0.56 to 1.36). This difference is clinically relevant favouring 0.5 units of oxytocin. However, in this study, the bolus was followed by a continuous infusion in both groups.
2. Shock (critical)
Not reported.
3. Maternal death (critical)
Not reported.
4. Blood transfusion (critical)
Not reported.
5. Blood loss (important)
Butwick (2010) reported that women who received 0.5 units of oxytocin had an estimated blood loss of 836 mL (SD=175) as compared to 697 mL (SD=120) for women who received 5 units of oxytocin (MD=139, 95%CI 31.62 to 246.38). This difference is not clinically relevant.
McDonagh (2022) reported that women who received 0.5 units of oxytocin had a median blood loss of 777 mL (IQR 492 to 1090 mL) as compared to 829 mL (IQR 503 to 1169) for women who received 5 units of oxytocin. This difference is not clinically relevant.
6. Use of additional uterotonics (important)
McDonagh (2022) reported that 7 of the 69 women (10%) who received 0.5 units of oxytocin needed additional uterotonics in the first 24 hours postoperatively as compared to 5 of the 69 women (7%) who received 5 units of oxytocin (RR=1.40, 95%CI 0.47 to 4.20). This difference is clinically relevant favouring 5 units of oxytocin.
7. Transfer for higher level of care (important)
Not reported.
8. Women's sense of wellbeing (important)
Not reported.
9. Acceptability and satisfaction with the intervention (important)
Not reported.
10. Breastfeeding (important)
Not reported.
11. Adverse effects (important)
McDonagh (2022) reported that 40 of the 69 women (58%) who received 0.5 units of oxytocin had experienced adverse effects as compared to 46 of the 69 (67%) of the women who received 5 units of oxytocin (RR=0.87, 95%CI 0.67 to 1.13). This difference is not clinically relevant.
11.1. Hypotension
Butwick (2010) reported that 4 of the 15 women (27%) who received 0.5 units of oxytocin had hypotension at 1 minute as compared to 7 of the 15 (47%) of the women who received 5 units of oxytocin (RR=0.57, 95%CI 0.21 to 1.55). This difference is clinically relevant favouring 0.5 units of oxytocin.
McDonagh (2022) reported that 21 of the 69 women (30%) who received either 0.5 units or 5 units of oxytocin had hypotension.
11.2. Nausea
Butwick (2010) reported that one women who received 5 units of oxytocin experienced nausea at 6 minutes (RD=-0.07, 95%CI -0.23 to 0.10).
McDonagh (2022) reported that 15 of the 69 women (21.7%) who received 0.5 units of oxytocin experienced nausea as compared to 20 of the 69 women (29%) who received 5 units of oxytocin (RR=0.75, 95%CI 0.42 to 1.34). This difference is clinically relevant favouring 0.5 units of oxytocin.
11.3. Vomiting
Butwick (2010) reported that no vomiting occurred.
McDonagh (2022) reported that 1 of the 69 women (2%) who received 5 units of oxytocin experienced vomiting, while this did not occur for women who received 0.5 units of oxytocin (RD=-0.01, 95%CI -0.05 to 0.02).
11.4. Chest pain
Butwick (2010) reported that no chest pain occurred.
McDonagh (2022) reported that 2 of the 69 women (3%) who received 0.5 units of oxytocin experienced chest pain as compared to 1 of the 69 women (2%) who received 5 units of oxytocin (RR=2.00, 95%CI 0.19 to 21.55). This difference is clinically relevant favouring 5 units of oxytocin.
11.5 Irregular heart beat
Butwick (2010) reported that no arrythmias occurred.
McDonagh (2022) reported that women who received either 0.5 or 5 units of oxytocin had no dysrhythmias.
12. PTSD
Not reported.
Level of evidence of the literature
According to GRADE, randomized controlled trials start at a high level of evidence.
The level of evidence regarding the outcome measure blood loss >1000 mL was downgraded to low because the 95% confidence interval crossed both lines of no (clinically relevant) effect (-2, imprecision).
The level of evidence regarding the outcome measure blood loss was downgraded to very low because of differences in the direction of the effect and assessment of the outcome (-1, inconsistency) and the optimal information size was not achieved (-1, imprecision).
The level of evidence regarding the outcome measure use of additional uterotonics was downgraded to low because the 95% confidence interval crossed both lines of no (clinically relevant) effect (-2, imprecision).
The level of evidence regarding the outcome measure adverse effects was downgraded to moderate because the 95% confidence interval crossed the line of no (clinically relevant) effect (-1, imprecision).
The level of evidence regarding the outcome measure hypotension was downgraded to very low because of differences in the direction of the effect (-1, inconsistency) and the 95% confidence interval crossed both lines of no (clinically relevant) effect (-2, imprecision).
The level of evidence regarding the outcome measure nausea was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure vomiting was downgraded to very low because of differences in the direction of the effect (-1, inconsistency) and the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure chest pain was downgraded to very low because of differences in the direction of the effect (-1, inconsistency) and the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure irregular heart beat was downgraded to very low because the optimal information size was not achieved and no events occurred
(-3, imprecision).
The level of evidence regarding the outcome measures shock, maternal death, blood transfusion, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and PTSD were not reported and therefore could not be assessed with GRADE.
Comparison 1 IU versus 5 IU
1. Blood loss >1000 mL (critical)
Not reported.
2. Shock (critical)
Not reported.
3. Maternal death (critical)
Not reported.
4. Blood transfusion (critical)
Not reported.
5. Blood loss (important)
Butwick (2010) reported that women who received 1 unit of oxytocin had an estimated blood loss of 764 mL (SD=237) as compared to 697 mL (SD=120) for women who received 5 units of oxytocin (MD= 67.00, 95%CI -71.20 to 205.20). This difference is not clinically relevant.
6. Use of additional uterotonics (important)
Butwick (2010) reported that one patient who received 1 unit of oxytocin needed additional uterotonics (i.m. methylergonovine maleate 0.2 mg at 9 minutes) (RD=0.07, 95%CI -0.10 to 0.25).
7. Transfer for higher level of care (important)
Not reported.
8. Women's sense of wellbeing (important)
Not reported.
9. Acceptability and satisfaction with the intervention (important)
Not reported.
10. Breastfeeding (important)
Not reported.
11. Adverse effects (important)
11.1. Hypotension
Butwick (2010) reported that 3 of the 14 women (21%) who received 1 unit of oxytocin had hypotension at 1 minute as compared to 7 of the 15 (47%) of the women who received 5 units of oxytocin (RR=0.46, 95%CI 0.15 to 1.44). This difference is clinically relevant favouring 1 unit of oxytocin.
11.2. Nausea
Butwick (2010) reported that one woman who received 5 units of oxytocin experienced nausea at 6 minutes (RD=-0.07, 95%CI -0.24 to 0.10).
11.3. Vomiting
Butwick (2010) reported that no vomiting occurred.
11.4. Chest pain
Butwick (2010) reported that no chest pain occurred.
11.5 Irregular heart beat
Butwick (2010) reported that no arrythmias occurred.
12. PTSD
Not reported.
Level of evidence of the literature
According to GRADE, randomized controlled trials start at a high level of evidence.
The level of evidence regarding the outcome measure blood loss was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure use of additional uterotonics was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure hypotension was downgraded to low because the 95% confidence interval crossed both lines of no (clinically relevant) effect (-2, imprecision).
The level of evidence regarding the outcome measure nausea was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure vomiting was downgraded to very low because the optimal information size was not achieved and no events occurred (-3, imprecision).
The level of evidence regarding the outcome measure chest pain was downgraded to very low because the optimal information size was not achieved and no events occurred (-3, imprecision).
The level of evidence regarding the outcome measure irregular heart beat was downgraded to very low because the optimal information size was not achieved and no events occurred
(-3, imprecision).
The level of evidence regarding the outcome measures blood loss >1000 mL, shock, maternal death, blood transfusion, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and PTSD were not reported and therefore could not be assessed with GRADE.
Comparison 2 IU versus 5 IU oxytocin
1. Blood loss >1000 mL (critical)
Not reported.
2. Shock (critical)
Not reported.
3. Maternal death (critical)
Not reported.
4. Blood transfusion (critical)
Not reported.
5. Blood loss (important)
Kim (2011) reported that women who received 2 units of oxytocin had an estimated blood loss of 450 mL (SD=13.9) as compared to 446.2 mL (SD=13.6) for women who received 5 units of oxytocin (MD=4.30, 95%CI -4.22 to 12.82). This difference is not clinically relevant.
Sartain (2008) reported that women who received 2 units of oxytocin had a median blood loss of 500 mL (range: 150 to 1200) as compared to 500 mL (range: 200 to 2000) for women who received 5 units of oxytocin.
6. Use of additional uterotonics (important)
Kim (2011) reported that 2 of the 20 women (10%) who received 2 units of oxytocin needed additional uterotonics as compared to 1 of the 20 women (5%) who received 5 units of oxytocin (RR=2.00, 95%CI 0.20 to 20.33). This difference is clinically relevant favouring 5 units of oxytocin.
Sartain (2008) reported that 7 of the 40 women (17.5%) who either received 2 units or 5 units of oxytocin needed additional uterotonics.
7. Transfer for higher level of care (important)
Not reported.
8. Women's sense of wellbeing (important)
Not reported.
9. Acceptability and satisfaction with the intervention (important)
Not reported.
10. Breastfeeding (important)
Not reported.
11. Adverse effects (important)
11.1. Hypotension
Not reported.
11.2. Nausea
Kim (2011) reported that 3 of the 20 women (15%) who received 2 units of oxytocin experienced nausea as compared to 5 of the 20 women (25%) who received 5 units of oxytocin (RR=0.60, 95%CI 0.17 to 2.18). This difference is clinically relevant favouring 2 units of oxytocin.
Sartain (2008) reported that 2 of the 40 women (5%) who received 2 units of oxytocin experienced nausea as compared to 13 of the 40 women (32.5%) who received 5 units of oxytocin (RR=0.15, 95%CI 0.04 to 0.64). This difference is clinically relevant favouring 2 units of oxytocin.
11.3. Vomiting
Kim (2011) reported that 1 of the 20 women (5%) who received 2 units of oxytocin experienced vomiting as compared to 3 of the 20 women (15%) who received 5 units of oxytocin (RR=0.33, 95%CI 0.04 to 2.94). This difference is clinically relevant favouring 2 units of oxytocin.
Sartain (2008) reported that 1 of the 40 women (2.5%) who received 2 units of oxytocin experienced vomiting as compared to 6 of the 40 women (15%) who received 5 units of oxytocin (RR=0.17, 95%CI 0.02 to 1.32). This difference is clinically relevant favouring 2 units of oxytocin.
11.4. Chest pain
Not reported.
11.5 Irregular heart beat
Not reported.
12. PTSD
Not reported.
Level of evidence of the literature
According to GRADE, randomized controlled trials start at a high level of evidence.
The level of evidence regarding the outcome measure blood loss was downgraded to very low because of concerns about randomization and allocation concealment (-1, risk of bias), differences in the assessment of the outcome (-1, inconsistency) and the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure use of additional uterotonics was downgraded to very low because of concerns about randomization and allocation concealment (-1, risk of bias), differences in the direction of the effect (-1, inconsistency) and the 95% confidence interval crossed both lines of no (clinically relevant) effect (-2, imprecision).
The level of evidence regarding the outcome measure nausea was downgraded to low because of concerns about randomization and allocation concealment (-1, risk of bias) and the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure vomiting was downgraded to very low because of concerns about randomization and allocation concealment (-1, risk of bias) and the 95% confidence interval crossed both lines of no (clinically relevant) effect (-2, imprecision).
The level of evidence regarding the outcome measures shock, maternal death, blood transfusion, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, hypotension, chest pain, irregular heart beat and PTSD were not reported and therefore could not be assessed with GRADE.
Comparison 3 IU versus 5 IU
1. Blood loss >1000 mL (critical)
Not reported.
2. Shock (critical)
Not reported.
3. Maternal death (critical)
Not reported.
4. Blood transfusion (critical)
Not reported.
5. Blood loss (important)
Butwick (2010) reported that women who received 3 units of oxytocin had an estimated blood loss of 707 mL (SD=117) as compared to 697 mL (SD=120) for women who received 5 units of oxytocin (MD=10.00, 95%CI -74.81 to 94.81). This difference is not clinically relevant.
Kothari (2018) reported that women who received 3 units of oxytocin had a mean blood loss of 878 mL (SD=146.09) as compared to 806 mL (SD=44.76) for women who received 5 units of oxytocin (MD=72.00, 95%CI 29.65 to 114.35). This difference is not clinically relevant.
6. Use of additional uterotonics (important)
Not reported.
7. Transfer for higher level of care (important)
Not reported.
8. Women's sense of wellbeing (important)
Not reported.
9. Acceptability and satisfaction with the intervention (important)
Not reported.
10. Breastfeeding (important)
Not reported.
11. Adverse effects (important)
11.1. Hypotension
Butwick (2010) reported that 4 of the 15 women (27%) who received 3 units of oxytocin had hypotension at 1 minute as compared to 7 of the 15 women (47%) who received 5 units of oxytocin (RR=0.57, 95%CI 0.21 to 1.55). This difference is clinically relevant favouring 3 units of oxytocin.
Kothari (2018) reported that 1 of the 50 women (2%) who received 3 units of oxytocin had hypotension as compared to 6 of the 50 women (12%) who received 5 units of oxytocin (RR=0.17, 95%CI 0.02 to 1.33). This difference is clinically relevant favouring 3 units of oxytocin.
11.2. Nausea
Butwick (2010) reported that one women who received 5 units of oxytocin experienced nausea at 6 minutes (RD=-0.07, 95%CI -0.23 to 0.10).
Kothari (2018) reported that 1 of the 50 women (2%) who received 5 units of oxytocin experienced nausea/vomiting, while this did not occur in women who received 3 units of oxytocin (RD=-0.02, 95%CI -0.07 to 0.03).
11.3. Vomiting
Butwick (2010) reported that no vomiting occurred.
Kothari (2018) reported that 1 of the 50 women (2%) who received 5 units of oxytocin experienced nausea/vomiting, while this did not occur in women who received 3 units of oxytocin (RD=-0.02, 95%CI -0.07 to 0.03).
11.4. Chest pain
Butwick (2010) reported that no chest pain occurred.
Kothari (2018) reported that 1 of the 50 women (2%) who received 5 units of oxytocin had chest pain, while this did not occur in women who received 3 units of oxytocin (RD=-0.02, 95%CI -0.07 to 0.03).
11.5 Irregular heart beat
Butwick (2010) reported that no arrythmias occurred.
12. PTSD
Not reported.
Level of evidence of the literature
According to GRADE, randomized controlled trials start at a high level of evidence.
The level of evidence regarding the outcome measure blood loss was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure hypotension was downgraded to low because the 95% confidence interval crossed both lines of no (clinically relevant) (-2, imprecision).
The level of evidence regarding the outcome measure nausea was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure vomiting was downgraded to very low because of differences in the direction of the effect (-1, inconsistency) and the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure chest pain was downgraded to very low because of differences in the direction of the effect (-1, inconsistency) and the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure irregular heart beat was downgraded to very low because the optimal information size was not achieved and no events occurred
(-3, imprecision).
The level of evidence regarding the outcome measures blood loss >1000 mL, shock, maternal death, blood transfusion, use of additional uterotonics, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and PTSD were not reported and therefore could not be assessed with GRADE.
Comparison 3 IU versus 10 IU
1. Blood loss >1000 mL (critical)
Not reported.
2. Shock (critical)
Not reported.
3. Maternal death (critical)
Not reported.
4. Blood transfusion (critical)
Not reported.
5. Blood loss (important)
Kothari (2018) reported that women who received 3 units of oxytocin had a mean blood loss of 878 mL (SD=146.09) as compared to 754 mL (SD=60.47) for women who received 10 units of oxytocin (MD=124, 95%CI 80.17 to 167.83). This difference is not clinically relevant favouring 10 units of oxytocin.
6. Use of additional uterotonics (important)
Not reported.
7. Transfer for higher level of care (important)
Not reported.
8. Women's sense of wellbeing (important)
Not reported.
9. Acceptability and satisfaction with the intervention (important)
Not reported.
10. Breastfeeding (important)
Not reported.
11. Adverse effects (important)
11.1. Hypotension
Kothari (2018) reported that 1 of the 50 women (2%) who received 3 units of oxytocin had hypotension as compared to 50 of the 50 (100%) of the women who received 10 units of oxytocin (RR=0.03, 95%CI 0.01 to 0.14). This difference is clinically relevant favouring 3 units of oxytocin.
11.2. Nausea/vomiting
Kothari (2018) reported that 13 of the 50 women (26%) who received 10 units of oxytocin experienced nausea/vomiting, while this did not occur in women who received 3 units of oxytocin (RD=-0.26, 95%CI -0.38 to -0.14).
11.4. Chest pain
Kothari (2018) reported that 4 of the 50 women (13.3%) who received 10 units of oxytocin had chest pain, while this did not occur in women who received 3 units of oxytocin (RD=-0.08, 95%CI -0.16 to 0.00).
11.5 Irregular heart beat
Not reported.
12. PTSD
Not reported.
Level of evidence of the literature
According to GRADE, randomized controlled trials start at a high level of evidence.
The level of evidence regarding the outcome measure blood loss was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure hypotension was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure nausea/vomiting was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measure chest pain was downgraded to low because the optimal information size was not achieved (-2, imprecision).
The level of evidence regarding the outcome measures blood loss >1000 mL, shock, maternal death, blood transfusion, use of additional uterotonics, transfer to higher level of care, women’s sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, irregular heart beat and PTSD were not reported and therefore could not be assessed with GRADE.
Zoeken en selecteren
A systematic review of the literature was performed to answer the following question:
What is the effect of administering a lower loading dose of oxytocin (< 5 IU IV) compared to a higher loading dose (≥ 5 IU IV) in women postpartum after vaginal delivery or caesarean section?
| P: patients | Women postpartum after vaginal delivery and caesarean section |
| I: intervention | Oxytocin < 5 IU iv |
| C: control | Oxytocin ³ 5 IU iv |
| O: outcome measure | Blood loss (dichotomous: >1000 mL or continuous), shock, maternal death, blood transfusion, use of additional uterotonics, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, adverse effects, PTSD |
Relevant outcome measures
The guideline development group considered blood loss > 1000 mL, shock, transfer for higher level of care, maternal death and blood transfusion as critical outcome measures for decision making; and blood loss as continuous outcome, use of additional uterotonics, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, adverse effects, and PTSD as important outcome measures for decision making.
The working group defined the outcome measure as follows:
- Adverse effects: hypotension, nausea/vomiting, chest pain and irregular heart beat/palpitations.
- Blood loss: number of patients with a blood loss >1000 mL or continuous outcome
For the other outcome measures, the working group did not define the outcome measures a priori but used the definitions used in the studies.
The working group defined a 1% difference in maternal death (RR < 0.99 or > 1.01) and 10% for the other critical outcome measures (RR<0.90 to >1.10) as a minimal clinically important difference. For the other outcomes, a 25% difference for dichotomous outcomes (RR < 0.8 or > 1.25) and 0.5 SD for continuous outcomes was taken as minimal clinically (patient) important difference.
Search and select (Methods)
The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from 2000 until October 18th, 2023. The detailed search strategy is depicted under the tab Methods. This resulted in 349 hits. Besides, on the 27th of May, 2024 an additional search was performed for systematic reviews. This resulted in 387 additional systematic reviews. Studies were selected based on the following criteria:
- Systematic reviews in which a minimum of 2 databases were searched and in which a detailed search strategy, in- and exclusion criteria, exclusion table, evidence table and risk of bias assessment are included, or randomized controlled trials (RCTs)
- Studying women after vaginal delivery and caesarean section
- Comparing oxytocin < 5 IU iv with oxytocin ³ 5 IU iv
- Assessing one or more of the predefined outcomes
Forty-eight studies were initially selected based on title and abstract screening. After reading the full text, forty-five studies were excluded (see the table with reasons for exclusion under the tab Methods), and three studies were included (McDonagh 2022; Tantry 2023; Phung, 2021). The systematic reviews of Tantry 2023 and Phung 2021 defined a broader PICO than the PICO defined for this module. Therefore, three randomized controlled trials included in Phung 2021 (Butwick 2010; Kim 2011; Sartain (2008)) and one study in Tantry 2023 (Kothari, 2018) were included. Besides, the RCT of McDonagh 2022 was included because it was published after the search date of Tantry 2023. In total, five studies were included. No studies were included about vaginal delivery.
Results
Five studies including three randomized controlled trials included in the systematic review of Phung 2021, one randomized controlled trial included in the systematic review of Tantry 2023 and one other randomized controlled trial were included in the analysis of the literature. Important study characteristics and results are summarized in the evidence tables and table 1. The assessment of the risk of bias is summarized in the risk of bias tables. All studies included women during cesarean section.
Referenties
- Butwick AJ, Coleman L, Cohen SE, Riley ET, Carvalho B. Minimum effective bolus dose of oxytocin during elective Caesarean delivery. Br J Anaesth. 2010 Mar;104(3):338-43. doi: 10.1093/bja/aeq004. PMID: 20150347.
- Kim TS, Bae JS, Park JM, Kang SK. Hemodynamic effects of continuous intravenous injection and bolus plus continuous intravenous injection of oxytocin in cesarean section. Korean J Anesthesiol. 2011 Dec;61(6):482-7. doi: 10.4097/kjae.2011.61.6.482. Epub 2011 Dec 20. PMID: 22220225; PMCID: PMC3249570.
- Kothari D, Bhalavi S, Gautam A, Choudhary B, Dahiya S, Pathak V. Effects of three doses of oxytocin (3, 5, 10 IU) on haemodynamic parameters, uterine tone and blood loss in elective caesarean section under spinal anaesthesia. A prospective randomised double-blind study. J. Evolution Med. Dent. Sci. 2018 Aug 27;17(35):3913-7.
- McDonagh F, Carvalho JCA, Abdulla S, Cordovani D, Downey K, Ye XY, Farine D, Morais M, Balki M. Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens. Anaesthesia. 2022 Aug;77(8):892-900. doi: 10.1111/anae.15714. Epub 2022 Mar 28. Erratum in: Anaesthesia. 2024 Feb;79(2):216-217. doi: 10.1111/anae.16196. PMID: 35343585.
- Phung LC, Farrington EK, Connolly M, Wilson AN, Carvalho B, Homer CSE, Vogel JP. Intravenous oxytocin dosing regimens for postpartum haemorrhage prevention following cesarean delivery: a systematic review and meta-analysis. Am J Obstet Gynecol. 2021 Sep;225(3):250.e1-250.e38. doi: 10.1016/j.ajog.2021.04.258. Epub 2021 May 4. PMID: 33957113.
- Sartain JB, Barry JJ, Howat PW, McCormack DI, Bryant M. Intravenous oxytocin bolus of 2 units is superior to 5 units during elective Caesarean section. Br J Anaesth. 2008 Dec;101(6):822-6. doi: 10.1093/bja/aen273. Epub 2008 Oct 9. PMID: 18845650.
- Tantry TP, Karanth H, Anniyappa S, Shetty PK, Upadya M, Shenoy SP, Kadam D. Intravenous oxytocin regimens in patients undergoing cesarean delivery: a systematic review and network meta-analysis of cluster-based groups. J Anesth. 2023 Apr;37(2):278-293. doi: 10.1007/s00540-022-03132-w. Epub 2022 Nov 16. PMID: 36385197.
Evidence tabellen
Research question: What is the most appropriate dose of oxytocin for the prevention of HPP?
|
Study reference |
Study characteristics |
Patient characteristics 2 |
Intervention (I) |
Comparison / control (C) 3
|
Follow-up |
Outcome measures and effect size 4 |
Comments |
|
Butwick, 2010 |
Type of study: Randomized, double-blind, placebo-controlled, dose-ranging study
Setting and country: Lucile Packard Children’s Hospital (Stanford, CA, USA),
Funding and conflicts of interest: The study was funded internally by the Department of Anesthesia, Stanford University School of Medicine. Conflict of interest was not reported.
|
Inclusion criteria: - Women between 18 and 40 years old - Singleton pregnancy - Term gestation: ³37 weeks - Elective caesarean delivery with a Pfannenstiel incision - ASA I or II
Exclusion criteria: - Active labor - Ruptured membranes - Known drug allergy to oxytocin - Multiple gestation - Significant obstetric disease (including pregnancy-induced hypertension or pre-eclampsia) - Known risk factors for postpartum hemorrhage (including abnormal placentation, multiple gestation, uterine fibroids, history of postpartum hemorrhage or uterine atony, and previous classical uterine incision), - Inherited or acquired coagulation disorder - Thrombocytopenia (platelet count <100x109)
N total at baseline: Intervention: 0.5 U: 15 1.0 U: 14 3.0 U: 15 Control: 15
Important prognostic factors2: Age (median; IQR): 0.5 U: 33 (31–34) 1.0 U: 35.5 (32–38) 3.0 U: 33 (30–36) 5.0 U: 32 (29–33)
Gestational age ± SD 0.5 U: 38.7 ± 1 1.0 U: 38.6 ± 0.6 3.0 U: 38.6 ± 0.7 5.0 U: 38.6 ± 0.8
Groups comparable at baseline.
|
0.5, 1.0 or 3.0 units of oxytocin
For both groups: “The oxytocin dose was prepared before surgery and diluted with 0.9% normal saline up to a total volume of 5 ml by an anaesthetist not involved in the study. Oxytocin was administered as an i.v. bolus over a time period of 15s after clamping of the umbilical cord and delivery of the fetus. After delivery of the fetus, the obstetrician manually removed the placenta and subsequently performed uterine massage. Uterine exteriorization was performed at the discretion of the attending obstetrician”.
“If the uterine tone was assessed as adequate at 2 min, then an oxytocin infusion was commenced [10 units oxytocin in 250 ml 0.9% normal saline at 125 ml/h (0.08 units/min)]. If the tone was assessed as inadequate, then a ‘rescue’ bolus of 2.5 units oxytocin was administered. A maximum of two ‘rescue’ doses of oxytocin were permitted in the event of two separate recordings of inadequate UT during the study period. If UT was assessed as inadequate after two rescue doses of oxytocin, then alternative uterotonic therapy was administered (i.m. methylergonovine maleate 0.2 mg; i.m. carboprost tromethamine 0.25 mg; rectal misoprostol 800–1000 mg) at the discretion of the attending anaesthetist and obstetrician. After the study period, all patients received a maintenance infusion of i.v. oxytocin (0.16 units/min)”.
“In the preoperative period, an 18 G peripheral i.v. cannula was inserted and all patients received 500 ml hetastarch (Hospira, Lake Forest, IL, USA) within 30 min before spinal anaesthesia. All patients were premedicated with i.v. metoclopramide 10 mg and ranitidine 50 mg. Spinal anaesthesia was performed at the L3–4 interspace with the patient in the sitting position with a 25 G Whitacre needle by an anesthetist who was not involved in the study. Women were given spinal anaesthesia with hyperbaric bupivacaine 1.6 ml (0.75%), fentanyl 10 mg, and morphine 200 mg. The patient was then moved to the supine position with left lateral uterine displacement. Surgery was allowed to proceed after achieving a T6 sensory level to pinprick”.
|
5 units of oxytocin |
Length of follow-up: Not reported
Loss-to-follow-up: No loss to follow-up
Incomplete outcome data: No incomplete outcome data
|
Estimated blood loss 0.5 units: 836 ml (SD=175) 1 unit: 764 ml (SD=237) 3 units: 707 ml (SD=117) 5 units: 697 ml (SD=120)
Additional uterotonics One patient in 1 unit group
Hypotension at 1 min 0.5 units: 4/15 (27%) 1 unit: 3/14 (21%) 3 units: 4/15 (27%) 5 units: 7/15 (47%)
Nausea at 6 min One patient in 5 units group
No vomiting, chest pain or arrythmias
|
Author’s conclusion “The routine use of 5 units oxytocin during elective CD can no longer be recommended, as adequate UT can occur with lower doses of oxytocin (0.5–3 units)”.
Limitations - Small sample sizes - Analyses of the oxytocin response and side-effects ≥2 min after administration may have also been confounded by patients receiving rescue doses of oxytocin |
|
Kim, 2011 |
Type of study: Randomized controlled trial
Setting and country: Korea
Funding and conflicts of interest: Not reported
|
Inclusion criteria: - Women with a gestational age of 38 weeks or more - Supposed to undergo planned cesarean section under spinal anesthesia - Classified as Class 1 or 2 according to the American Society of Anesthesiologist (ASA) physical status classification
Exclusion criteria: - Contraindications for spinal anesthesia - Weight of 100 kg or higher - Fetal abnormalities - Diabetes - Gestational hypertension - Cardiovascular disease - Cerebral hemorrhage - Women whose labor pain had already started
N total at baseline: Intervention: 20 Control: 20
Important prognostic factors2: Age ± SD: I: 31.1 ± 3.1 years C: 31.0 ± 2.8 years
Gestational age ± SD I: 38.7 ± 0.7 weeks C: 38.6 ± 1.0 weeks
Groups comparable at baseline.
|
Bolus of 2 IU oxytocin
Both groups “Bolus intravenous injection of 2 IU or 5 IU of oxytocin diluted with 5 ml of normal saline was done at a rate of 1 ml/sec, and then continuous intravenous injection of 10 IU of oxytocin diluted with 40 ml of normal saline was done at a rate of 0.25 IU/min for 40 minutes with a syringe pump”.
“About 500 ml of Hartmann solution was rapidly dripped into all the parturient women before inducing anesthesia. For the spinal anesthesia, the L3-4 or L4-5 lumbar region was punctured with a 25 G Quincke needle when the parturient women were in the left lateral recumbent position, and 0.5% hyperbaric bupivacaine solution (10-12 mg) was injected after verifying the cerebrospinal fluid leakage. Immediately after the anesthesia, the parturient women were asked to take the supine position and the maximum sensory block level was set to T4-6. When some of the parturient women had severe vomiting or continual nausea, the antiemetic drug, ondansetron 8 mg, was intravenously injected. In the cases where the systolic pressure decreased by more than 20% compared to the blood pressure before coming to the operating room, 10 mg of ephedrine was intravenously injected until the blood pressure was normalized, and these cases were excluded from the study”
|
Bolus of 5 IU oxytocin |
Length of follow-up: Not reported
Loss-to-follow-up: No loss to follow-up
Incomplete outcome data: No incomplete outcome data
|
Blood loss I: 450.5 ± 13.9 ml C: 446.2 ± 13.6 ml
Additional uterotonic treatment I: 2/20 (10%) C: 1/20 (5%)
Nausea I: 3/20 (15%) C: 5/20 (25%)
Vomiting I: 1/20 (5%) C: 3/20 (15%) |
Author’s conclusion “Two IU bolus-continuous injection showed lower hemodynamic changes than in the five IU bolus-continuous injection”.
Limitations Low number of participants |
|
Kothari, 2018 |
Type of study: Prospective, randomized, double-blind study.
Setting and country: India
Funding and conflicts of interest: Source of funding not reported. No financial or other competing interest.
|
Inclusion criteria: Pregnant women between 18 and 35 years with singleton pregnancies who had ASA grade I or II and who received elective Lower Segment Caesarean Section
Exclusion criteria: - Active labor - Ruptured membranes - Known drug allergy to oxytocin - Multiple gestations - Pregnancy-induced hypertension/ preeclampsia - High-risk cases for postpartum hemorrhage - Inherited or acquired coagulation disorder and thrombocytopenia (platelet count <100x109) - Significant cardiorespiratory diseases
N total at baseline: Intervention: 3 IU: 50 Control: 5 IU: 50 10 IU: 50
Important prognostic factors2: Age (mean ± SD): 3 IU: 25.56±2.72 years 5 IU: 25.06±2.96 years 10 IU: 24.62±2.67 years
Groups comparable at baseline.
|
3 IU of oxytocin mixed with 100 mL NS infused over a period of 2 - 4 minutes after fetoplacental delivery
For both groups: “All the patients were kept nil orally for 6 hours before procedure. Upon arrival of the patient in the operation theatre, intravenous access with two 18-G cannula was established and preloading was done with ringer lactate 10-15 mL/kg body wt. within 20 mins before spinal anesthesia from one intravenous cannula”.
“In operating room, all the patients were uniformly premedicated with Inj. Ranitidine 50 mg + Inj. Metoclopramide 10 mg + Inj. Ondansetron 4 mg IV before induction of anesthesia”.
“With all aseptic precautions, Spinal Anaesthesia (SA) was performed in left lateral position by a 25-G Quincke type lumbar puncture needle and hyperbaric bupivacaine 2 - 2.2 mL was injected in subarachnoid L3-L4 space. Immediately, patient was moved to the supine position and left lateral uterine displacement of uterus was done with a wedge. Surgery was allowed to proceed after achieving a T6 sensory level to pinprick. After delivery of foetus and placenta, the study dose of Oxytocin prepared in 100 mL was administered as an IV infusion over a time period of 2 - 4 mins by an anaesthesiologist who took no further part in the study. Each episode of hypotension was treated with an IV bolus of 6 mg Mephentermine and increasing the rate of crystalloid infusion. Bradycardia was treated with Inj. Atropine sulphate 0.3 mg IV. If uterine tone was inadequate after 6 minutes of study dose, the rescue dose of 2.5 units of Oxytocin was given on the request of operating surgeon. 5 IU of oxytocin in 500 mL of NS was given as slow infusion over 8 hours in the post-operative ward as per hospital protocol”.
|
5 or 10 IU of oxytocin mixed with 100 mL NS infused over a period of 2 - 4 minutes after fetoplacental delivery |
Length of follow-up: Not reported
Loss-to-follow-up: No loss to follow-up
Incomplete outcome data: No incomplete outcome data
|
Blood loss 3 IU: 878.00 ± 146.09 mL 5 IU: 806 ± 44.76 mL 10 IU: 754 ± 60.47 mL
Hypotension 3 IU: 1/50 (2%) 5 IU: 6/50 (12%) 10 IU: 50/50 (100%)
Chest pain/ghabrahat 3 IU: 0 5 IU: 1/50 (2%) 10 IU: 4/50 (13.3%)
Nausea/vomiting/flushing 3 IU: 0 5 IU: 1/50 (2%) 10 IU: 13/50 (26%) |
Author’s conclusion “Administration of 5 IU oxytocin as intravenous infusion in elective caesarean section resulted in adequate uterine tone, stable hemodynamic parameters, lesser blood loss and self-limiting side-effects as compared to 3 and 10 IU”.
Limitations Population not generalizable; Indian population and the study enrolled only parturient posted for elective caesarean deliveries that had minimum clinical risk PPH due to uterine atony. Requirement of oxytocin may be different in active labor. |
|
McDonagh, 2022 |
Type of study: Double-blind, randomized, controlled, non-inferiority trial
Setting and country: Two centers in Ontario, Canada.
Funding and conflicts of interest: Researchers were supported by a Merit Award from the University of Toronto. No other external funding or competing interests were declared. |
Inclusion criteria: Pregnant women with a gestational age between 37+0 to 40+6 weeks who underwent elective caesarean delivery under spinal anesthesia
Exclusion criteria: - Allergy or hypersensitivity to oxytocin or carbetocin - Active labor - Requirement for general anesthesia - BMI ≥40 kg/m2 - Conditions predisposing to uterine atony and postpartum hemorrhage (such as placenta previa, multiple gestation, (pre-)eclampsia, macrosomia, polyhydramnios, uterine fibroids, previous history of uterine atony and postpartum hemorrhage, bleeding diathesis, and hepatic, renal or cardiovascular disease). - Women who refused to give written informed consent
N total at baseline: Intervention: 69 Control: 69
Important prognostic factors2: Age ± SD: I: 34.8 ± 4.0 years C: 35.1 ± 4.0 years
Gestational age ± SD I: 38.8 ± 0.6 weeks C: 38.7 ± 0.8 weeks
Groups probably comparable at baseline
|
Low-dose oxytocin: 0.5 IU bolus + infusion of 40 mIU/min
For both groups: “Spinal anaesthesia was performed in the sitting position using a 25- or 27-gauge Whitacre needle. A mixture of hyperbaric bupivacaine 12–13.5 mg, fentanyl 10 lg and morphine 100 lg was given intrathecally over 30 s. The women were then positioned in the supine position with left uterine displacement achieved by placing a wedge under the right buttock”
“Immediately after the umbilical cord was clamped, the study drug (diluted to 10 ml with normal saline) was administered as an intravenous bolus over 1 min and the study infusion was commenced. Women allocated to the oxytocin groups received 20 IU oxytocin in 1 l Ringer’s lactate solution at a rate of 120 ml.h-1 (40 mIU.min-1)”
“Women received either paracetamol 1.3 g per rectum before leaving the operating theatre or 1 g orally in the post-anaesthesia care unit. All women received intravenous ketorolac 30 mg. They were observed for 2 h in the post-anaesthesia care unit”.
|
High-dose oxytocin: 5 IU bolus + infusion of 40 mIU/min
|
Length of follow-up: Up to 24 hours after delivery
Loss-to-follow-up: No loss to follow-up
Incomplete outcome data: No incomplete outcome data
|
Use of additional uterotonics (first 24 h postoperative) I: 7/69 (10%) C: 5/69 (7%)
Blood loss ((median (IQR [range])) I: 777 (492 to 1090) C: 829 (503 to 1169)
Blood loss >1000 mL I: 23/68 (34%) C: 26/67 (39%)
Adverse effect I: 40/69 (58%) C: 46/69 (67%)
Hypotension I: 21/69 (30%) C: 21/69 (30%)
Nausea I: 15/69 (21.7%) C: 20/69 (29%)
Vomiting I: 0 C: 1/69 (2%)
Chest pain I: 2/69 (3%) C: 1/69 (2%)
Dysrhythmia I: 0 C: 0
|
Authors’ conclusion: “Low-dose oxytocin (0.5 IU) was non-inferior to high-dose oxytocin (5 IU) for the primary and secondary outcomes of uterine tone intensity at 2, 5 and 10 min after drug administration in elective caesarean delivery. Low-dose and high-dose regimens were associated with a similar need for additional uterotonics, blood loss and adverse effects”.
Limitations - Blood loss estimation may not have been accurate, as it was based on a formula which used pre- and postoperative hematocrit and the patient’s weight |
|
Sartain, 2008 |
Type of study: Randomized, double-blind trial
Setting and country: Australia
Funding and conflicts of interest: Not reported
|
Inclusion criteria: Women undergoing elective caesarean section under regional anesthesia who received either 2 or 5 u of intravenous oxytocin after delivery
Exclusion criteria: - Women with an increased risk of uterine atony or excessive bleeding (more than two previous caesarean sections, a history of previous post-partum hemorrhage, known placenta previa or accreta, twin pregnancy, and polyhydramnios) - Cardiovascular instability (pre-eclampsia or essential hypertension).
N total at baseline: Intervention: 40 Control: 40
Important prognostic factors2: Age (range): I: 30.8 (20–40) years C: 30.9 (21–41) years
Groups were comparable at baseline. |
2 U i.v. bolus of oxytocin after delivery, followed by an oxytocin infusion of 10 U/h for 4 hours
For both groups: “All women received famotidine 40 mg both the night before and the morning of surgery. All women received a combined spinal–epidural anaesthetic in the sitting position with hyperbaric bupivacaine 0.5% (2.3 ml) and fentanyl 10 mg given intrathecally. After securing the epidural catheter, women were laid supine with a wedge under the right flank to achieve a leftward tilt of 15º. One liter of Hartmann’s solution was then rapidly infused over 10–15 min, with further i.v. fluids given at the discretion of the anesthetist. A phenylephrine solution 100 mg/ml was infused initially at 30 ml/h (3 mg/h) and titrated to maintain mean arterial pressure (MAP) within 10% of the level before anesthesia”.
|
5 U i.v. bolus of oxytocin after delivery, followed by an oxytocin infusion of 10 U/h for 4 hours |
Length of follow-up: 4 hours after delivery
Loss-to-follow-up: No loss to follow-up
Incomplete outcome data: No incomplete outcome data |
Blood loss I: 500 (150–1200) ml C: 500 (200–2000) ml
Additional uterotonic treatment overall I: 7/40 (17.5%) C: 7/40 (17.5%)
Nausea I: 2/40 (5%) C: 13/40 (32.5%)
Vomiting I: 1/40 (2.5%) C: 6/40 (15%) |
Author’s conclusion “In elective Caesarean section, a 2 u bolus of oxytocin results in less haemodynamic change than 5 u, with less nausea and no difference in the need for additional uterotonics”.
Limitations Only included elective patients at low risk of postoperative bleeding
|
Risk of bias table for intervention studies
Research question: What is the most appropriate dose of oxytocin for the prevention of HPP?
|
Study reference
(first author, publication year) |
Was the allocation sequence adequately generated?
Definitely yes Probably yes Probably no Definitely no |
Was the allocation adequately concealed?
Definitely yes Probably yes Probably no Definitely no |
Blinding: Was knowledge of the allocated interventions adequately prevented?
Were patients blinded?
Were healthcare providers blinded?
Were data collectors blinded?
Were outcome assessors blinded?
Were data analysts blinded?
Definitely yes Probably yes Probably no Definitely no |
Was loss to follow-up (missing outcome data) infrequent?
Definitely yes Probably yes Probably no Definitely no |
Are reports of the study free of selective outcome reporting?
Definitely yes Probably yes Probably no Definitely no |
Was the study apparently free of other problems that could put it at a risk of bias?
Definitely yes Probably yes Probably no Definitely no |
Overall risk of bias If applicable/necessary, per outcome measure
LOW Some concerns HIGH
|
|
Butwick, 2010 |
Definitely yes;
Reason: Random number allocations were used.
|
Definitely yes;
Reason: Opaque envelopes containing group assignments were used to ensure blinding of the investigators.
|
Definitely yes;
Reason: Double-blinded trial. The obstetrician and anesthetist involved in each case were blinded to the oxytocin dose assignments. |
Probably yes;
Reason: No loss to follow-up or missing data. |
Probably yes;
Reason: All relevant outcome measures were reported. |
Probably yes;
Reason: No other problems noted. |
LOW |
|
Kim, 2011 |
Probably yes;
Reason: Women were randomly divided, but method was not reported. |
No information |
Probably yes;
Reason: Oxytocin injection prepared by nurse who did not participate in the study. |
Probably yes;
Reason: No loss to follow-up or missing data. |
Probably yes;
Reason: Not clearly stated, but all relevant outcomes were reported. |
Probably yes;
Reason: No other problems noted. |
Some concerns |
|
Kothari, 2018 |
Definitely yes;
Reason: Computer-generated codes (random numbers) were used for random allocation.
|
Definitely yes;
Reason: Allocation concealment was achieved by placing the randomization sequence for each technique (random numbers) in sequentially numbered, sealed, opaque envelopes.
|
Definitely yes;
Reason: Double-blinded trial. Drug administrator and monitoring observer along with obstetrician were kept blinded to both drug and the patient thus avoiding observer’s bias. The anaesthesiologist who infused the study drug took no further part in the study. |
Probably yes;
Reason: No loss to follow-up or missing data. |
Probably yes;
Reason: All relevant outcomes were reported. |
Probably yes;
Reason: No other problems noted. |
LOW |
|
McDonagh, 2022 |
Definitely yes;
Reason: Randomly allocated by a research coordinator using computer-generated block randomization with a block size of eight. |
Definitely yes;
Reason: Opaque, sealed envelopes were used and opened by an anesthetist or research assistant who was not involved in the care of the patient. |
Definitely yes;
Reason: Double-blinded trial. The patient, anaesthetist and obstetrician were blinded to the study drug and infusion administered. |
Definitely yes;
Reason: No loss to follow-up or missing data. |
Definitely yes;
Reason: All relevant outcomes were reported. |
Probably yes;
Reason: No other problems noted. |
LOW |
|
Sartain, 2008 |
Probably yes;
Reason: Random numbers were generated. |
Definitely yes;
Reason: Random numbers in sealed envelopes were used. Doctor not involved in care of the patient or any data recordings prepared the oxytocin doses. |
Definitely yes;
Reason: Double-blind trial. Each anesthetist and obstetrician was blinded.
|
Definitely yes;
Reason: No loss to follow-up or missing data. |
Probably yes;
Reason: Not clearly stated, but all relevant outcomes were reported. |
Probably no;
Reason: Included only elective patients at low risk of postoperative bleeding. |
LOW |
Table of excluded studies
|
Reference |
Reason for exclusion |
|
Balki M, Ronayne M, Davies S, Fallah S, Kingdom J, Windrim R, Carvalho JC. Minimum oxytocin dose requirement after cesarean delivery for labor arrest. Obstet Gynecol. 2006 Jan;107(1):45-50. doi: 10.1097/01.AOG.0000191529.52596.c0. PMID: 16394038. |
Other study aim: determine effective dose |
|
Baliuliene V, Vitartaite M, Rimaitis K. Prophylactic Dose of Oxytocin for Uterine Atony during Caesarean Delivery: A Systematic Review. Int J Environ Res Public Health. 2021 May 10;18(9):5029. doi: 10.3390/ijerph18095029. PMID: 34068723; PMCID: PMC8126197. |
Better systematic review with same studies available |
|
Ben Tareef A, Downey K, Ma B, Whittle WL, Carvalho JCA. Carbetocin versus oxytocin following vaginal and Cesarean delivery: a before-after study. Can J Anaesth. 2022 Jan;69(1):97-105. English. doi: 10.1007/s12630-021-02127-7. Epub 2021 Oct 28. PMID: 34713434. |
Wrong comparison: carbetocin versus oxytocin |
|
Biradar AM, Yaliwal RG, Kori SS, Mathapati SS, Shiragur SS, Mudanur SR. Randomised Control Trial of 3 IU Intravenous Oxytocin Bolus With 7 IU Oxytocin Infusion Versus 10 IU Intramuscular Oxytocin in the Third Stage of Labour in the Prevention of Postpartum Hemorrhage. |
Wrong comparison: IV versus IM oxytocin |
|
Carvalho JC, Balki M, Kingdom J, Windrim R. Oxytocin requirements at elective cesarean delivery: a dose-finding study. Obstet Gynecol. 2004 Nov;104(5 Pt 1):1005-10. doi: 10.1097/01.AOG.0000142709.04450.bd. PMID: 15516392. |
Wrong study aim: determine effective dose |
|
Cecilia M, Vijayaselvi R, Bansal R, Lakshmi L, Jose R. Ten units intravenous oxytocin over 2-4 h is as effective as 30 units over 8-12 h in preventing postpartum hemorrhage after cesarean section: A randomized controlled trial. Indian J Pharmacol. 2018 Sep-Oct;50(5):279-283. doi: 10.4103/ijp.IJP_419_18. PMID: 30636832; PMCID: PMC6302697. |
Wrong comparison: 10 units over 2-4 hours versus 30 units over 8-12 hours |
|
Dagraca J, Malladi V, Nunes K, Scavone B. Outcomes after institution of a new oxytocin infusion protocol during the third stage of labor and immediate postpartum period. Int J Obstet Anesth. 2013 Jul;22(3):194-9. doi: 10.1016/j.ijoa.2013.03.007. Epub 2013 May 18. PMID: 23692707. |
Retrospective study (before and after protocol change) |
|
Doyle JL, Kenny TH, Gothard MD, Seagraves E, McCarroll M, Silber A. A Standardized Oxytocin Administration Protocol After Delivery to Reduce the Treatment of Postpartum Hemorrhage. Jt Comm J Qual Patient Saf. 2019 Feb;45(2):131-143. doi: 10.1016/j.jcjq.2018.05.007. Epub 2018 Aug 29. PMID: 30172662. |
Observational study |
|
Duffield A, McKenzie C, Carvalho B, Ramachandran B, Yin V, El-Sayed YY, Riley ET, Butwick AJ. Effect of a High-Rate Versus a Low-Rate Oxytocin Infusion for Maintaining Uterine Contractility During Elective Cesarean Delivery: A Prospective Randomized Clinical Trial. Anesth Analg. 2017 Mar;124(3):857-862. doi: 10.1213/ANE.0000000000001658. PMID: 28212181; PMCID: PMC5319709. |
Wrong comparison: first all groups received the same bolus dose and then different infusion rates |
|
Foley A, Gunter A, Nunes KJ, Shahul S, Scavone BM. Patients Undergoing Cesarean Delivery After Exposure to Oxytocin During Labor Require Higher Postpartum Oxytocin Doses. Anesth Analg. 2018 Mar;126(3):920-924. doi: 10.1213/ANE.0000000000002401. PMID: 28858899. |
Wrong comparison: exposed versus unexposed to oxytocin |
|
Gallos ID, Williams HM, Price MJ, Merriel A, Gee H, Lissauer D, Moorthy V, Tobias A, Deeks JJ, Widmer M, Tunçalp Ö, Gülmezoglu AM, Hofmeyr GJ, Coomarasamy A. Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst Rev. 2018 Apr 25;4(4):CD011689. doi: 10.1002/14651858.CD011689.pub2. Update in: Cochrane Database Syst Rev. 2018 Dec 19;12:CD011689. doi: 10.1002/14651858.CD011689.pub3. PMID: 29693726; PMCID: PMC6494487. |
Other study aim: identify most effective and cost-effective uterotonic drugs |
|
Gallos I, Williams H, Price M, Pickering K, Merriel A, Tobias A, Lissauer D, Gee H, Tunçalp Ö, Gyte G, Moorthy V, Roberts T, Deeks J, Hofmeyr J, Gülmezoglu M, Coomarasamy A. Uterotonic drugs to prevent postpartum haemorrhage: a network meta-analysis. Health Technol Assess. 2019 Feb;23(9):1-356. doi: 10.3310/hta23090. PMID: 30821683; PMCID: PMC6421507. |
Other study aim: identify most effective and cost-effective uterotonic drugs |
|
George RB, McKeen D, Chaplin AC, McLeod L. Up-down determination of the ED(90) of oxytocin infusions for the prevention of postpartum uterine atony in parturients undergoing Cesarean delivery. Can J Anaesth. 2010 Jun;57(6):578-82. doi: 10.1007/s12630-010-9297-1. Epub 2010 Mar 18. PMID: 20238255. |
Wrong study aim: determine effective dose |
|
Holleboom CA, van Eyck J, Koenen SV, Kreuwel IA, Bergwerff F, Creutzberg EC, Bruinse HW. Carbetocin in comparison with oxytocin in several dosing regimens for the prevention of uterine atony after elective caesarean section in the Netherlands. Arch Gynecol Obstet. 2013 Jun;287(6):1111-7. doi: 10.1007/s00404-012-2693-8. Epub 2013 Jan 18. PMID: 23329341; PMCID: PMC3655222. |
Wrong comparison: carbetocin versus oxytocin |
|
Kiran S, Anand A, Singh T, Gupta N. To estimate the minimum effective dose of oxytocin required to produce adequate uterine tone in women undergoing elective caesarean delivery. Egyptian Journal of Anaesthesia. 2013 Apr 1;29(2):161-5. |
Wrong intervention: 0.5, 1 or 2 unit oxytocin |
|
Kotze A, Adam Y, Naidoo P. Maternal outcomes before and after new oxytocin protocol at cesarean delivery. Int J Gynaecol Obstet. 2022 Aug;158(2):368-376. doi: 10.1002/ijgo.13966. Epub 2021 Nov 6. PMID: 34606091. |
Retrospective study (before and after protocol change) |
|
Lavoie A, McCarthy RJ, Wong CA. The ED90 of prophylactic oxytocin infusion after delivery of the placenta during cesarean delivery in laboring compared with nonlaboring women: an up-down sequential allocation dose-response study. Anesth Analg. 2015 Jul;121(1):159-164. doi: 10.1213/ANE.0000000000000781. PMID: 25902327. |
Wrong comparison: women scheduled for intrapartum cesarean delivery after prior exposure to exogenous oxytocin versus women scheduled for elective cesarean delivery |
|
McKenna DS, Rudinsky K, Sonek J. Effects of a new patient safety-driven oxytocin dosing protocol on postpartum hemorrhage. J Pregnancy. 2014;2014:157625. doi: 10.1155/2014/157625. Epub 2014 Apr 27. PMID: 24868465; PMCID: PMC4020156. |
Wrong comparison: 40 units versus 30 units of oxytocin |
|
Mohta M, Chowdhury RB, Tyagi A, Agarwal R. Efficacy of different infusion rates of oxytocin for maintaining uterine tone during elective caesarean section: A randomised double blind trial. Anaesth Intensive Care. 2021 May;49(3):183-189. doi: 10.1177/0310057X20984480. Epub 2021 May 2. PMID: 33934618. |
Wrong comparison: first all groups received the same bolus dose and then different infusion rates |
|
Mohta M, Siddiqui S, Chilkoti GT, Agarwal R. Oxytocin infusion rates for maintaining uterine tone during non-elective cesarean section in laboring patients: a randomized, controlled trial. J Anesth. 2022 Aug;36(4):456-463. doi: 10.1007/s00540-022-03067-2. Epub 2022 Apr 29. PMID: 35484429. |
First all groups received the same slow IU and then infusion |
|
Oguz Orhan E, Dilbaz B, Aksakal SE, Altınbas S, Erkaya S. Prospective randomized trial of oxytocin administration for active management of the third stage of labor. Int J Gynaecol Obstet. 2014 Nov;127(2):175-9. doi: 10.1016/j.ijgo.2014.05.022. Epub 2014 Jul 17. PMID: 25108586. |
Wrong comparison: after delivery of fetus versus when anterior shoulder seen |
|
Oladapo OT, Okusanya BO, Abalos E. Intramuscular versus intravenous prophylactic oxytocin for the third stage of labour. Cochrane Database Syst Rev. 2012 Feb 15;(2):CD009332. doi: 10.1002/14651858.CD009332.pub2. Update in: Cochrane Database Syst Rev. 2018 Sep 22;9:CD009332. doi: 10.1002/14651858.CD009332.pub3. PMID: 22336865. |
Wrong comparison: intravenous versus intramuscular |
|
Oladapo OT, Okusanya BO, Abalos E. Intramuscular versus intravenous prophylactic oxytocin for the third stage of labour. Cochrane Database Syst Rev. 2018 Sep 22;9(9):CD009332. doi: 10.1002/14651858.CD009332.pub3. Update in: Cochrane Database Syst Rev. 2020 Nov 9;11:CD009332. doi: 10.1002/14651858.CD009332.pub4. PMID: 30246877; PMCID: PMC6513632. |
Wrong comparison: intravenous versus intramuscular |
|
Oladapo OT, Okusanya BO, Abalos E, Gallos ID, Papadopoulou A. Intravenous versus intramuscular prophylactic oxytocin for the third stage of labour. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD009332. doi: 10.1002/14651858.CD009332.pub4. PMID: 33169839; PMCID: PMC8236306. |
Wrong comparison: intravenous versus intramuscular |
|
Ortiz-Gómez JR, Morillas-Ramírez F, Fornet-Ruiz I, Palacio-Abizanda FJ, Bermejo-Albares L. Estudio clínico y farmacoeconómico de la eficacia de la carbetocina en cesáreas electivas respecto a la oxitocina a dosis bajas y a dosis habituales [Clinical and pharmacological study of the efficacy of carbetocin in elective caesareans compared to low and usual doses of oxytocin]. Rev Esp Anestesiol Reanim. 2013 Jan;60(1):7-15. Spanish. doi: 10.1016/j.redar.2012.06.013. Epub 2012 Nov 1. PMID: 23122840. |
Article in Spanish |
|
Palacio FJ, Morillas F, Ortiz-Gómez JR, Fornet I, Bermejo L, Cantalejo F. Eficacia de la oxitocina a dosis bajas en cesáreas electivas [Efficacy of low-dose oxytocin during elective cesarean section]. Rev Esp Anestesiol Reanim. 2011 Jan;58(1):6-10. Spanish. doi: 10.1016/s0034-9356(11)70691-0. PMID: 21348211. |
Article in Spanish |
|
Parry Smith WR, Papadopoulou A, Thomas E, Tobias A, Price MJ, Meher S, Alfirevic Z, Weeks AD, Hofmeyr GJ, Gülmezoglu AM, Widmer M, Oladapo OT, Vogel JP, Althabe F, Coomarasamy A, Gallos ID. Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst Rev. 2020 Nov 24;11(11):CD012754. doi: 10.1002/14651858.CD012754.pub2. PMID: 33232518; PMCID: PMC8130992. |
Wrong comparison: misoprostol (plus oxytocin) verus oxytocin |
|
Peska E, Balki M, Maxwell C, Ye XY, Downey K, Carvalho JCA. Oxytocin at elective caesarean delivery: a dose-finding study in women with obesity. Anaesthesia. 2021 Jul;76(7):918-923. doi: 10.1111/anae.15322. Epub 2020 Nov 23. PMID: 33227150. |
Other study aim: dose-finding |
|
Peska E, Balki M, Pfeifer W, Maxwell C, Ye XY, Downey K, Carvalho JCA. Oxytocin at Elective Cesarean Delivery: A Dose-Finding Study in Pregnant People With Twin Pregnancy. Anesth Analg. 2024 Apr 1;138(4):814-820. doi: 10.1213/ANE.0000000000006309. Epub 2022 Dec 8. PMID: 36480452. |
Other study aim: dose-finding |
|
Pursche T, Diedrich K, Banz-Jansen C. Blood loss after caesarean section: depending on the management of oxytocin application? Arch Gynecol Obstet. 2012 Sep;286(3):633-6. doi: 10.1007/s00404-012-2334-2. Epub 2012 May 9. PMID: 22569708. |
Wrong comparison: Bolus with infusion versus only infusion |
|
Qian XW, Drzymalski DM, Lv CC, Guo FH, Wang LY, Chen XZ. The ED50 and ED95 of oxytocin infusion rate for maintaining uterine tone during elective caesarean delivery: a dose-finding study. BMC Pregnancy Childbirth. 2019 Dec 31;20(1):6. doi: 10.1186/s12884-019-2692-x. PMID: 31892352; PMCID: PMC6937915. |
Wrong comparison: first all groups received the same bolus dose and then different infusion rates |
|
Rosseland LA, Bekkenes M, Jørgensen MM, Flem Jacobsen A, Wang Fagerland M, Rakstad-Larsen H, Solberg OG, Aaberge L, Klingenberg O, Steinsvik T. A study protocol for the cardiac effects of a single dose of either oxytocin 2.5 IU or carbetocin 100 g after caesarean delivery: A prospective randomized controlled multi-centre trial in Norway. F1000Research - Volume 10, Issue 0 |
Wrong study design: study protocol |
|
Salati JA, Leathersich SJ, Williams MJ, Cuthbert A, Tolosa JE. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage. Cochrane Database Syst Rev. 2019 Apr 29;4(4):CD001808. doi: 10.1002/14651858.CD001808.pub3. PMID: 31032882; PMCID: PMC6487388. |
Wrong comparison: oxytocin versus no uterotonics or placebo |
|
Sheehan SR, Montgomery AA, Carey M, McAuliffe FM, Eogan M, Gleeson R, Geary M, Murphy DJ; ECSSIT Study Group. Oxytocin bolus versus oxytocin bolus and infusion for control of blood loss at elective caesarean section: double blind, placebo controlled, randomised trial. BMJ. 2011 Aug 1;343:d4661. doi: 10.1136/bmj.d4661. PMID: 21807773; PMCID: PMC3148015. |
Wrong comparison: adding oxytocin infusion to bolus oxytocin versus only oxytocin bolus |
|
Somjit M, Surojananon J, Kongwattanakul K, Kasemsiri C, Sirisom M, Prawannoa K, Thepsuthammarat K, Komwilaisak R. Comparison of Low Dose versus High Dose of Oxytocin for Initiating Uterine Contraction During Cesarean Delivery: A Randomized, Controlled, Non-Inferiority Trial. Int J Womens Health. 2020 Aug 24;12:667-673. doi: 10.2147/IJWH.S260073. PMID: 32904472; PMCID: PMC7455765. |
Wrong comparison: 5 UI versus 10 UI |
|
Stålberg V, Josefsson A, Bladh M, Lilliecreutz C. The risk of postpartum hemorrhage when lowering the oxytocin dose in planned cesarean section, a pilot study. Sex Reprod Healthc. 2021 Sep;29:100641. doi: 10.1016/j.srhc.2021.100641. Epub 2021 Jun 11. PMID: 34174496. |
Observational study |
|
Stephens LC, Bruessel T. Systematic review of oxytocin dosing at caesarean section. Anaesth Intensive Care. 2012 Mar;40(2):247-52. doi: 10.1177/0310057X1204000206. PMID: 22417018. |
More a narrative review without risk of bias assessment. Included also unsuitable studies for PICO |
|
Terblanche N, Otahal P, Messmer A, Wright P, Patel S, Nathan K, Sharman JE. An observational cohort study of 3 units versus 5 units slow intravenous bolus oxytocin in women undergoing elective caesarean delivery. J Physiol Pharmacol. 2017 Aug;68(4):547-553. PMID: 29151071. |
Observational study |
|
Terblanche NCS, Picone DS, Otahal P, Sharman JE. Paucity of evidence for the effectiveness of prophylactic low-dose oxytocin protocols (<5 IU) compared with 5 IU in women undergoing elective caesarean section: A systematic review of randomised controlled trials. Eur J Anaesthesiol. 2018 Dec;35(12):987-989. doi: 10.1097/EJA.0000000000000853. PMID: 30376493; PMCID: PMC6226213. |
No included studies matching with PICO |
|
Tita AT, Szychowski JM, Rouse DJ, Bean CM, Chapman V, Nothern A, Figueroa D, Quinn R, Andrews WW, Hauth JC. Higher-dose oxytocin and hemorrhage after vaginal delivery: a randomized controlled trial. Obstet Gynecol. 2012 Feb;119(2 Pt 1):293-300. doi: 10.1097/AOG.0b013e318242da74. PMID: 22227638; PMCID: PMC3282278. |
Wrong comparison: 10 units, 40 units, 80 units |
|
Torloni MR, Siaulys M, Riera R, Cabrera Martimbianco AL, Leite Pacheco R, Latorraca COC, Widmer M, Betrán AP. Timing of oxytocin administration to prevent post-partum hemorrhage in women delivered by cesarean section: A systematic review and metanalysis. PLoS One. 2021 Jun 3;16(6):e0252491. doi: 10.1371/journal.pone.0252491. PMID: 34081734; PMCID: PMC8174699. |
Other study aim: timing of oxytocin administration (before versus after fetal delivery) |
|
Tyagi S, Tyagi A, Rashmi S, Mohta M, Gupta B. Weight-based oxytocin infusion for preventing uterine atony during caesarean delivery in non-labouring patients: A dose-response study. Clin Exp Pharmacol Physiol. 2023 Jun;50(6):497-503. doi: 10.1111/1440-1681.13766. Epub 2023 Mar 8. PMID: 36846888. |
Other study aim: dose-response study |
|
Wang LY, Wang J, Dong JH, Ping ZP, Chen XZ, Wei CN. The optimal oxytocin infusion rate for preventing uterine atony during cesarean delivery in elderly parturients with prior history of cesarean delivery. Front Pharmacol. 2023 Jul 28;14:1211693. doi: 10.3389/fphar.2023.1211693. PMID: 37576820; PMCID: PMC10416618. |
Concerns a specific patient group, not generalizable |
|
Wei CN, Deng JL, Dong JH, Ping ZP, Chen XZ. The Median Effective Dose of Oxytocin Needed to Prevent Uterine Atony During Cesarean Delivery in Elderly Parturients. Drug Des Devel Ther. 2020 Dec 8;14:5451-5458. doi: 10.2147/DDDT.S258651. PMID: 33335388; PMCID: PMC7737550. |
Wrong comparison: old versus young parturients |
|
Yaliwal RG, Biradar AM, Dharmarao PS, Kori SS, Mudanur SR, Patil NG, Shiragur SS, Mathapati SS. A Randomized Control Trial of 3 IU IV Oxytocin Bolus with 7 IU Oxytocin Infusion versus 10 IU Oxytocin Infusion During Cesarean Section for Prevention of Postpartum Hemorrhage. Int J Womens Health. 2020 Nov 18;12:1091-1097. doi: 10.2147/IJWH.S280842. PMID: 33239923; PMCID: PMC7680681. |
Wrong comparison: bolus + infusion versus only infusion |
Verantwoording
Beoordelingsdatum en geldigheid
Publicatiedatum : 12-12-2025
Beoordeeld op geldigheid : 12-12-2025
Algemene gegevens
De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd door de Stichting Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.
Samenstelling werkgroep
Voor het ontwikkelen van de richtlijnmodule is in 2022 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met haemorrhagia postpartum.
Werkgroep
- Dr. M.(Martina) Porath (voorzitter) (NVOG)
- Dr. H.C.J. (Liesbeth) Scheepers (NVOG)
- Dr. D.D.C.A. (Dacia) Henriquez (NVOG)
- Dr. J.M. (Annemieke) Middeldorp(NVOG)
- Prof. dr. T.H. (Thomas) van den Akker (NVOG)
- Dr. P. (Paul) Ramler (NVOG) (tot September 2023)
- Dr. K.P.M. (Karin) van Galen(NIV)
- Drs. H.W. (Hannah) de Klerk (KNOV)
- Drs. L. (Lianne) Zondag (KNOV)
- Prof. dr. ir. Y.M.C. (Yvonne) Henskens (NVKC)
- Dr. I.C.M. (Ingrid) Beenakkers (NVA)
- Dr. S. (Simone) Willems (NVA)
- Mw. I. (Ilse) van Ee (PFN)
Klankboardgroep
- Drs. K. (Klaartje) Caminada (AZN)
- Mw. B. (Britt) Ketelaars (PFN)
Met ondersteuning van
- Dr. M. (Mohammadreza) Abdollahi, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
- Dr. I.M. (Irina) Mostovaya, senior adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
- Dr. J. (Jana) Tuijtelaars, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
- Drs. D.A.M. (Danique) Middelhuis, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
- Dr. M. (Majke) van Bommel, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
- Dr. L. (Leanne) Küpers, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
- Drs. D.A.M. (Fieke) Pepping, junior adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
- Linda Niesink, medisch informatie specialist, Kennisinstituut van de Federatie Medisch Specialisten
- Laura Boerboom, medisch informatie specialist, Kennisinstituut van de Federatie Medisch Specialisten
- Alies Oost, medisch informatie specialist, Kennisinstituut van de Federatie Medisch Specialisten
Belangenverklaringen
Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.
|
Naam |
Hoofdfunctie |
Nevenwerkzaamheden |
Persoonlijke financiële belangen |
Persoonlijke relaties |
Extern gefinancierd onderzoek |
Intellectuele belangen en reputatie |
Overige belangen |
Datum |
Restrictie |
|
Martina Porath |
gynaecoloog-perinatoloog Maxima Medisch Centrum |
Voorzitter focusgroep Acute Verloskunde Noord-Brabant Lid NVOG werkgroep Otterlo |
geen |
geen |
geen |
geen |
geen |
04/28/2025 |
|
|
Liesbeth Scheepers |
perinatoloog MUMC |
Richtlijnen commissie Otterloo groep Voorzitter Regioconsortium Geboortezorg Limburg Vice voorzitter Perinatale audit Limburg |
Geen |
Nee |
ZONMW onderzoek, niet op dit onderwerp |
Nee |
Nee |
04/25/2025 |
|
|
Annemieke Middeldorp |
Gynaecoloog Perinatoloog Leids Universitair Medisch Centrum, gestopt met werken vanaf 2024 |
geen |
geen |
geen |
geen |
geen |
geen |
04/25/2025 |
|
|
Dacia Henriquez |
Gynaecoloog, Perinatoloog, Amphia Ziekenhuis |
Geen |
Geen |
Geen |
Geen |
Geen |
Geen |
04/28/2025 |
|
|
Thomas van den Akker |
Gynaecoloog perinatoloog, LUMC, hoogleraar Verloskunde |
Hoogleraar VU *Global Maternal Health, Athena Instituut. *Perined bestuurslid *RvT Wemos. *FMG Pijlervoorzitter NVOG *Vz working party for international safe motherhood and reproductive health. *Perinatale audit regiovoorzitter. Alles onbetaald. |
Geen |
Geen |
Geen |
Door werk van de commissie komt het werk van mijn voormalig promovendi Ada Gillissen en Paul Ramler meer in de aandacht staan, omdat sommige aanbevelingen hierop gebaseerd zijn (met name van laatstgenoemde ten aanzien van ballon versus embolisatie).
Het feit dat ik als bijdrager op de richtlijn sta kan gezien worden als ten goede komend aan de boegbeeldfunctie die ik bij de NVOG heb, maar het effect hiervan lijkt beperkt in het licht van mijn andere activiteiten. |
Geen |
04/25/2025 |
|
|
Paul Ramler (tot September 2023) |
AIOS Gynaecologie, cluster Leiden |
Geen |
Geen |
Geen |
Geen |
Geen |
Geen |
29/01/2023 |
|
|
Ingrid Beenakkers |
Anesthesioloog, UMCU/WKZ |
geen |
geen |
geen |
geen |
geen |
geen |
04/28/2025 |
|
|
Simone Anna Alexandra Sijm-Willems |
Anesthesioloog Radboudumc |
- |
-zs |
- |
- |
- |
- |
04/25/2025 |
|
|
Karin van Galen |
internist-hematoloog UMC Utrecht |
geen |
geen |
n.v.t. |
Octapharma: Pregnancy and inherited bleeding disorders - unresticted research grant, projectleider. |
Voorzitter Nederlands Zorgnetwerk Vrouwen met een stollingsstoornis. Tot Febr 2025 voorzitter Women and Girls with beleeding Disorders Group European Assosiation for Heamophilia and Alied Disorders - momenteel nog actief lid van deze werkgroep. |
n.v.t. |
04/25/2025 |
|
|
Yvonne Henskens |
Klinisch chemicus, waarnemend hoofd Centraal Diagnostisch Laboratorium Hoogleraar Klinische Chemie ihb Hemostase |
Voorzitter Vereniging Hematologisch Laboratoria 2020-heden Lid Vici beoordelingscie 2022 Lid raad van Advies NVKC 2023-heden Adviseur Promicol 2020-heden |
geen |
geen |
Voor alle studies in het kader van mijn leerstoel worden reagentia of apparatuur gratis of met korting verkregen, hierbij wordt geen enkele IVD methode of bedrijf uitgesloten mits het past in het doel van mijn leerstoel. Noyons stipendium NVKC (prijs) Stago / Validatie van apparatuur en/of reagentia / Ja Siemens / Validatie van apparatuur en/of reagentia / Ja Werfen / Validatie van apparatuur en/of reagentia / N Nodia / Validatie van apparatuur en/of reagentia / Nee Promicol / Validatie van apparatuur en/of reagentia / Nee |
nee |
nee |
04/25/2025 |
|
|
Hannah de Klerk |
Zelfstandig eerstelijns verloskundige (ZZP), betaald PhD aanstelling Amsterdam UMC, locatie VUMc, onbetaald |
Gastdocent HU, betaald Projectleider KNOV, betaald |
geen |
nee |
nee |
nee |
nee |
7/10/2022 |
|
|
Lianne Zondag |
Eerstelijns verloskundige - verloskundige praktijk de Toekomst - Geldermalsen KNOV - senior richtlijnonwikkelaar |
Bestuurslid Netwerk Geboortezorg Rivierenland PhD candidate Maastricht University |
Geen |
Geen |
Geen |
Geen |
Geen |
2/6/2023 |
|
|
Ilse van Ee |
Adviseur Patientenbelang - full time inbreng patientenperspectief |
Ervaringsdeskundige patientvertegenwoordiger - Eupati - fellow Psoriasispatienten Nederland - onbetaald Coordinator Patientenpraticipatie, lid centrale redactie Psoriasispatienten Nederland - onbetaald Eupati mentor - Eupati Nl - onbetaald |
nee |
nvt |
Janssen / Freedom of disease Psoriasis / ja |
nee |
nvt |
04/25/2025 |
|
|
Klaartje Caminada |
Medisch Manager Ambulancezorg, lid protocollencommissie Ambulancezorg Nederland |
geen |
geen |
geen |
geen |
geen |
geen |
04/29/2025 |
|
|
Brit Ketelaars |
Adviseur patiëntbelang bij Patiëntenfederatie Nederland (full time, betaald) |
geen |
geen |
geen |
geen |
geen |
geen |
04/25/2025 |
|
Inbreng patiëntenperspectief
De werkgroep besteedde aandacht aan het patiëntenperspectief door uitnodigen van Patiëntenfederatie Nederland, Geboortebeweging en Het Buikencollectiefvoor de invitational conference. Het verslag hiervan is besproken in de werkgroep. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptrichtlijn is tevens voor commentaar voorgelegd aan Patiëntenfederatie Nederland en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.
Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz
Bij de richtlijnmodule voerde de werkgroep conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uit om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).
Uit de kwalitatieve raming blijkt dat er waarschijnlijk mogelijk substantiële financiële gevolgen zijn, zie onderstaande tabel.
In Nederland bevallen per jaar ca. 160.000 vrouwen. De incidentie van haemorrhagia postpartum is 7 tot 10%. Dit zijn 11.200 tot 16.000 vrouwen per jaar. Het aantal vrouwen met risicofactoren voor HPP is niet bekend.
| Module |
Uitkomst raming |
Toelichting |
|
Dosering van oxytocine ter preventie van HPP |
geen financiële gevolgen |
De dosis van de bolus oxytocine wordt verlaagd. |
Werkwijze
Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.
Zoekverantwoording
Literature search strategy
|
Richtlijn: Richtlijn Modulaire actualisatie richtlijn Hemorrhagia Postpartum (HPP) |
|
|
Uitgangsvraag: Wat is de meest aangewezen dosis oxytocine ter preventie van HPP? |
|
|
Database(s): Medline (OVID), Embase |
Datum: 18-10-2023 |
|
Periode: > 2000 |
Talen: geen beperking |
|
Literatuurspecialist: Laura Boerboom |
|
|
BMI zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ Bij gebruikmaking van een volledig zoekblok zal naar de betreffende link op de website worden verwezen. |
|
|
Toelichting en opmerkingen:
→ Voor deze vraag is gezocht op de elementen HPP (in het blauw), oxytocine (in het groen) en dosis (in het rood).
→ Van de drie sleutelpublicaties zitten er twee in de resultaten, namelijk het artikel van Salati (2019) en Oladapo (2020). Het artikel van Begley (2019) zit niet in de resultaten omdat het geen oxytocine bespreekt in het abstract.
→ Resultaten staan in Rayyan.
|
|
|
Te gebruiken voor richtlijnen tekst: In de databases Embase (via embase.com) en Medline (via OVID) is op 18-10-2023 met relevante zoektermen gezocht naar systematic reviews, RCT’s en observationele studies over wat de meest aangewezen dosis oxytocine is ter preventie van HPP. De literatuurzoekactie leverde 322 unieke treffers op. |
|
Zoekopbrengst
|
|
EMBASE |
OVID/MEDLINE |
Ontdubbeld |
|
SR’s |
72 |
45 |
63 |
|
RCT’s |
171 |
96 |
182 |
|
Observationele studies |
75 |
38 |
77 |
|
|
318 |
179 |
322 |
Zoekstrategie
|
Database |
Zoektermen |
|||||||||||||||||||||||||||||||||||||||
|
Embase
|
|
|||||||||||||||||||||||||||||||||||||||
|
Medline (OVID)
|
1 exp Postpartum Hemorrhage/ or 'fluxus postpartum'.ti,ab,kf. or 'postpartum hemorrhage'.ti,ab,kf. or 'post partum haemorrhage'.ti,ab,kf. or 'post partum hemorrhage'.ti,ab,kf. or 'postpartal haemorrhage'.ti,ab,kf. or 'postpartal hemorrhage'.ti,ab,kf. or 'postpartum bleeding'.ti,ab,kf. or 'postpartum haemorrhage'.ti,ab,kf. or 'puerperal haemorrhage'.ti,ab,kf. or 'puerperal hemorrhage'.ti,ab,kf. or ('blood loss' adj6 (postpartum or 'post partum' or delivery or cesarean)).ti,ab,kf. or 'obstetric* bleeding'.ti,ab,kf. or 'obstetric* hemorrhage'.ti,ab,kf. or 'obstetric* haemorrhage'.ti,ab,kf. (14189)
|
|
Richtlijn: Richtlijn Modulaire actualisatie richtlijn Hemorrhagia Postpartum (HPP) |
|
|
Uitgangsvraag: Wat is de meest aangewezen dosis oxytocine ter preventie van HPP? |
|
|
Database(s): Medline (OVID), Embase |
Datum: 27-05-2024 |
|
Periode: > 2000 |
Talen: geen beperking |
|
Literatuurspecialist: Laura Boerboom |
|
|
BMI zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ Bij gebruikmaking van een volledig zoekblok zal naar de betreffende link op de website worden verwezen. |
|
|
Toelichting en opmerkingen:
→ Voor deze vraag is gezocht op de elementen Vrouwen postpartum na vaginale baring (in het blauw) en oxytocine (in het groen).
→ Van de drie sleutelpublicaties zitten er twee in de resultaten, namelijk het artikel van Salati (2019) en Oladapo (2020). Het artikel van Begley (2019) zit niet in de resultaten omdat het geen oxytocine bespreekt in het abstract.
→ Resultaten staan in Rayyan.
|
|
|
Te gebruiken voor richtlijnen tekst: In de databases Embase (via embase.com) en Medline (via OVID) is op 27-05-2024 met relevante zoektermen gezocht naar systematic reviews over wat de meest aangewezen dosis oxytocine is ter preventie van HPP. De literatuurzoekactie leverde 387 unieke treffers op. |
|
Zoekopbrengst
|
|
EMBASE |
OVID/MEDLINE |
Ontdubbeld |
|
SR’s |
280 |
326 |
387 |
|
Ontdubbeld met eerdere set |
239 |
290 |
349 |
Zoekstrategie
|
Database |
Zoektermen |
|||||||||||||||||||||
|
Embase
|
|
|||||||||||||||||||||
|
Medline (OVID)
|
1 exp *Oxytocin/ or oxytocin*.ti,ab,kf. or ocytocin.ti,ab,kf. or syntocinon.ti,ab,kf. or pitocin.ti,ab,kf. (28826) |