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BMC Pregnancy and Childbirth Mar 2020Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention...
BACKGROUND
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality in low- and middle-income countries (LMICs). Oxytocin and misoprostol are used for the prevention and treatment of PPH. However, both medicines are chemically unstable and sensitive to environmental conditions. Previous studies reported a high prevalence of substandard oxytocin and misoprostol preparations in LMICs.
METHODS
In randomly selected health facilities of four districts of Malawi, the availability of oxytocin and misoprostol was determined, and the knowledge of health workers on storage requirements and use of oxytocics was assessed. Temperature loggers were used to record the storage temperature of oxytocics. Samples of oxytocin injections and misoprostol tablets were collected from the health facilities and from wholesalers. Oxytocin samples were analysed for identity, assay (= quantity of oxytocin) and for pH value according to United States Pharmacopeia 40. Misoprostol samples were analysed for identity, assay, dissolution and related substances according to the International Pharmacopeia 2017.
RESULTS
All visited hospitals and health centers had oxytocin available. At non-refrigerated storage sites, the recorded mean kinetic temperature exceeded the oxytocic's storage temperature stated on the labels in 42% of the sites. At refrigerated storage sites, the required temperature of 2-8 °C was exceeded in 33% of the sites. Out of 65 oxytocin samples, 7 (11%) showed moderate deviations from specification, containing 82.2-86.8% of the declared amount of oxytocin. Out of 30 misoprostol samples, 5 (17%) showed extreme deviations, containing only 12.7-30.2% of the declared amount. The extremely substandard misoprostol was reported to the national authorities and to WHO, leading to an immediate recall of the respective brand in Malawi. The UK-based distributor of this brand closed its business shortly thereafter.
CONCLUSION
Availability of oxytocin was excellent in Malawi, and its quality was better than reported in previous studies in other LMICs. However, storage conditions at the health facilities often did not meet the requirements. Extremely substandard misoprostol tablets were found, representing a serious risk to maternal health. This shows the need for continued efforts for quality assurance in medicine procurement and registration, as well as for post-marketing surveillance.
Topics: Drug Storage; Health Facilities; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Malawi; Misoprostol; Oxytocics; Oxytocin; Quality Assurance, Health Care; Quality Control
PubMed: 32223759
DOI: 10.1186/s12884-020-2810-9 -
Midwifery Aug 2023Both duration of labour and use of oxytocin for augmentation are known risk factors for postpartum haemorrhage but distinguishing between the significance of these... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Both duration of labour and use of oxytocin for augmentation are known risk factors for postpartum haemorrhage but distinguishing between the significance of these factors is complex. In this study, we aimed to investigate the association between both labour duration and oxytocin augmentation, for postpartum haemorrhage.
DESIGN
A cohort study based on a secondary analysis of a cluster-randomised trial.
PARTICIPANTS AND SETTING
Term nulliparous women with a single foetus in cephalic presentation, spontaneous onset of active labour and a vaginal birth. The participants were originally included in cluster-randomised trial conducted in Norway from December 1, 2014, to January 31, 2017, that aimed to compare the frequency of intrapartum caesarean sections when adhering to the WHO partograph versus Zhang's guideline.
MEASUREMENTS
The data were analysed through four statistical models. Model 1 investigated the effect of oxytocin augmentation as a dichotomous variable (yes/no); Model 2 investigated the effect of the duration of oxytocin augmentation; Model 3 investigated the effect of the maximum dose of oxytocin; and Model 4 investigated the effect of both the duration of augmentation and the maximum dose of oxytocin. All four models included duration of labour divided into five time-intervals. We used binary logistic regression to estimate the odds ratios of postpartum haemorrhage, defined as blood loss of ≥ 1000 ml, including a random intercept for hospital and mutually adjusting for oxytocin augmentation and labour duration in addition to maternal age, maternal marital status, maternal higher education level, maternal smoking habits in the first trimester, maternal body mass index and birth weight.
FINDINGS
Model 1 found a significant association between the use of oxytocin and postpartum haemorrhage. In Model 2, oxytocin augmentation of ≥ 4.5 h was associated with postpartum haemorrhage. In Model 3, we found an association between a maximum dose of oxytocin of ≥ 20 mU/min and postpartum haemorrhage. Model 4 showed that a maximum dose of oxytocin ≥ 20 mU/min was associated with postpartum haemorrhage both for those augmented < 4.5 h and for those augmented ≥ 4.5 h. Duration of labour was associated with postpartum haemorrhage in all models if lasting ≥ 16 h.
KEY CONCLUSIONS
We found both oxytocin augmentation and labour duration to be associated with postpartum haemorrhage. Oxytocin doses of ≥ 20 mU/min and a labour duration of ≥ 16 h showed an independent association.
IMPLICATION FOR PRACTICE
The potent drug oxytocin should be carefully administered, as doses of ≥ 20 mU/min were associated with an increased risk of PPH, regardless of the duration of oxytocin augmentation.
Topics: Pregnancy; Female; Humans; Oxytocin; Postpartum Hemorrhage; Oxytocics; Cohort Studies; Labor, Obstetric
PubMed: 37244235
DOI: 10.1016/j.midw.2023.103705 -
The Cochrane Database of Systematic... Oct 2010Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue widely used for off-label indications such as induction of abortion and of labour. This is one of a series... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue widely used for off-label indications such as induction of abortion and of labour. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology.
OBJECTIVES
To determine the effects of vaginal misoprostol for third trimester cervical ripening or induction of labour.
SEARCH STRATEGY
The Cochrane Pregnancy and Childbirth Group's Trials Register (November 2008) and bibliographies of relevant papers. We updated this search on 30 April 2010 and added the results to the awaiting classification section.
SELECTION CRITERIA
Clinical trials comparing vaginal misoprostol used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods.
DATA COLLECTION AND ANALYSIS
We developed a strategy to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction.We used fixed-effect Mantel-Haenszel meta-analysis for combining dichotomous data.If we identified substantial heterogeneity (I² greater than 50%), we used a random-effects method.
MAIN RESULTS
We included 121 trials. The risk of bias must be kept in mind as only 13 trials were double blind.Compared to placebo, misoprostol was associated with reduced failure to achieve vaginal delivery within 24 hours (average relative risk (RR) 0.51, 95% confidence interval (CI) 0.37 to 0.71). Uterine hyperstimulation, without fetal heart rate (FHR) changes, was increased (RR 3.52 95% CI 1.78 to 6.99).Compared with vaginal prostaglandin E2, intracervical prostaglandin E2 and oxytocin, vaginal misoprostol was associated with less epidural analgesia use, fewer failures to achieve vaginal delivery within 24 hours and more uterine hyperstimulation. Compared with vaginal or intracervical prostaglandin E2, oxytocin augmentation was less common with misoprostol and meconium-stained liquor more common.Lower doses of misoprostol compared to higher doses were associated with more need for oxytocin augmentation and less uterine hyperstimulation, with and without FHR changes.We found no information on women's views.
AUTHORS' CONCLUSIONS
Vaginal misoprostol in doses above 25 mcg four-hourly was more effective than conventional methods of labour induction, but with more uterine hyperstimulation. Lower doses were similar to conventional methods in effectiveness and risks. The authors request information on cases of uterine rupture known to readers. The vaginal route should not be researched further as another Cochrane review has shown that the oral route of administration is preferable to the vaginal route. Professional and governmental bodies should agree guidelines for the use of misoprostol, based on the best available evidence and local circumstances.
Topics: Administration, Intravaginal; Cervical Ripening; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Pregnancy Trimester, Third; Randomized Controlled Trials as Topic
PubMed: 20927722
DOI: 10.1002/14651858.CD000941.pub2 -
PloS One 2021Sustainable Development Goal 3.1 calls for a reduction of the maternal mortality ratio to less than 70 per 100,000 live births by 2030. The most important cause of...
Sustainable Development Goal 3.1 calls for a reduction of the maternal mortality ratio to less than 70 per 100,000 live births by 2030. The most important cause of maternal mortality is post-partum haemorrhage (PPH). Oxytocin injections and misoprostol tablets are medicines of first choice for the management of PPH in low- and middle-income countries (LMICs). Unfortunately, both substances are chemically unstable, and previous studies have revealed serious quality problems of these medicines in LMICs. The present study is the first report on their quality in Rwanda. From 40 randomly selected health facilities (hospitals, health centers, retail pharmacies and private clinics) in different parts of Rwanda, as well as from six wholesalers and government stores, oxytocin injections and misoprostol tablets were collected. Oxytocin storage temperatures in the health facilities were monitored for six months using temperature data loggers, and found to correctly follow the storage requirements stated by the manufacturers (2-8°C, or room temperature) with few minor deviations. Oxytocin injections (57 samples, representing seven batches of four brands) were tested for their oxytocin content and pH value according to the United States Pharmacopeia. Twenty-four samples from three European manufacturers passed all tests. However, all nine samples of one batch of a Chinese manufacturer showed an excessive content of oxytocin (range 117.2-121.5% of the declared amount). Another batch of the same manufacturer showed extreme variations of the concentration of the preservative benzyl alcohol. Misoprostol tablets (25 samples, representing ten batches of six brands) were tested for content and dissolution according to the International Pharmacopoeia. Fifteen samples passed, but all 10 samples of two brands from India failed with extreme deviations, containing only 42.5-48.7% of the stated amount of misoprostol. In conclusion, oxytocin quality in Rwanda was better than reported from other African countries. However, two extremely substandard brands of misoprostol tablets were found. The Rwandan authorities reacted quickly and efficiently, and recalled these substandard medicines from the market. For oxytocin and misoprostol, with their well-known problems of quality and stability, procurement should possibly be restricted to medicines which are WHO-prequalified or which have been manufactured in countries with stringent regulatory authorities.
Topics: Drug Storage; Health Facilities; Humans; Oxytocics; Quality Assurance, Health Care; Quality Control; Rwanda
PubMed: 33417602
DOI: 10.1371/journal.pone.0245054 -
PloS One 2020To compare synthetic oxytocin infusion regimens used during labour, calculate the International Units (IU) escalation rate and total amount of IU infused over eight... (Review)
Review
OBJECTIVE
To compare synthetic oxytocin infusion regimens used during labour, calculate the International Units (IU) escalation rate and total amount of IU infused over eight hours.
DESIGN
Observational study.
SETTING
Twelve countries, eleven European and South Africa.
SAMPLE
National, regional or institutional-level regimens on oxytocin for induction and augmentation labour.
METHODS
Data on oxytocin IU dose, infusion fluid amount, start dose, escalation rate and maximum dose were collected. Values for each regimen were converted to IU in 1000ml diluent. One IU corresponded to 1.67μg for doses provided in grams/micrograms. IU hourly dose increase rates were based on escalation frequency. Cumulative doses and total IU amount infused were calculated by adding the dose administered for each previous hour. Main Outcome Measures Oxytocin IU dose infused.
RESULTS
Data were obtained on 21 regimens used in 12 countries. Details on the start dose, escalation interval, escalation rate and maximum dose infused were available from 16 regimens. Starting rates varied from 0.06 IU/hour to 0.90 IU/hour, and the maximum dose rate varied from 0.90 IU/hour to 3.60 IU/hour. The total amount of IU oxytocin infused, estimated over eight hours, ranged from 2.38 IU to 27.00 IU, a variation of 24.62 IU and an 11-fold difference.
CONCLUSION
Current variations in oxytocin regimens for induction and augmentation of labour are inexplicable. It is crucial that the appropriate minimum infusion regimen is administered because synthetic oxytocin is a potentially harmful medication with serious consequences for women and babies when inappropriately used. Estimating the total amount of oxytocin IU received by labouring women, alongside the institution's mode of birth and neonatal outcomes, may deepen our understanding and be the way forward to identifying the optimal infusion regimen.
Topics: Drug Administration Schedule; Europe; Female; Humans; Labor, Induced; Labor, Obstetric; Oxytocics; Oxytocin; Practice Guidelines as Topic; Pregnancy
PubMed: 32722667
DOI: 10.1371/journal.pone.0227941 -
Journal de Gynecologie, Obstetrique Et... Dec 2011Define methods of induction of labour for the population of pregnant women at the end of 41 SA and beyond, including membranes sweeping, mechanical and pharmacological... (Review)
Review
OBJECTIVES
Define methods of induction of labour for the population of pregnant women at the end of 41 SA and beyond, including membranes sweeping, mechanical and pharmacological procedures as oxytocin, prostaglandin E1 (misoprostol) and E2 (dinoprostone) and other methods as well for the scarred uterus.
METHODS
Bibliographic research done by consulting databases PubMed, and Cochrane.
RESULTS
Membrane sweeping reduces by 41% the need of induction of labour at 41 SA and 72% for postterm (42 SA). Membrane sweeping is a technique with some discomfort for the patient but has advantages. This procedure should not be imposed on patients in a systematic visit because it presents inconveniences (contractions, bleeding, pain). Oxytocin remains the gold standard used for labour induction and requires well-codified rationale protocols in maternity for increasing doses. Most of the trials show that this product is appropriate when the cervix is considered as favorable (Bishop ≥ 6). In the presence of intact membranes, induction by oxytocin must be associated with amniotomy for a significant reduction in "induction-delivery" period. The Foley catheter is a mechanically reliable, reproducible method for inducing labour with less uterine hyperstimulation without increasing the rate of caesarean sections. It is an interesting process but maternal and neonatal infectious morbidity appears to be possibly increased. The non-vaginal PGE2 (cervical) are no longer recommended. The PGE2 vaginal gel or pessary are comparable methods to induce labour. They can be used to successfully induce labour regardless of cervical Bishop score. In case of unfavorable cervical conditions, PGE2 can reduce the use of oxytocin and decrease the required doses. Misoprostol is a molecule that may be proposed for induction of labour provided to know the doses, risks and side effects and to adapt materno-fetal monitoring. The optimal route of administration remains yet to be assessed because of a higher risk of hyperstimulation or tachysystole. Initial doses should be 25 μg. However, misoprostol did not have the authorization in this indication and merit some caution when using it. Prostaglandin E1 is associated with a high risk of uterine rupture and should not be used after caesarean section. Acupuncture, homeopathy NO donors, breast stimulation or sexual intercourse are methods ineffective in all conditions or assessment is insufficient to conclude with evidence based medicine.
CONCLUSION
In postterm, different procedures could be performed for induction of labour. Furthermore membrane sweeping, oxytocin is the drug of choice for induction on favourable cervix and one of the most commonly used drugs. Vaginal prostaglandins E2 are effective whatever the cervical conditions. Misoprostol is a very interesting pharmacological molecule without authorization in this indication but has real advantages on efficacy, cost, storage and administration. Other studies with high power have to remain on track and to focus on the optimal and route doses because of increased risk of tachysystole or hyperstimulation with effects on the FHR. Minimal doses at 25μg seem to be safe. The Foley catheter is a reliable method without any pharmacological effect and opening interesting perspectives but with caution about the possible increased infectious risks.
Topics: Biomechanical Phenomena; Diagnostic Techniques, Obstetrical and Gynecological; Female; Humans; Labor, Induced; Oxytocics; Oxytocin; Pregnancy; Pregnancy Complications; Pregnancy, Prolonged; Prognosis
PubMed: 22056188
DOI: 10.1016/j.jgyn.2011.09.021 -
Archives of Gynecology and Obstetrics Sep 2023Misoprostol is a synthetic PGE analogue that is used for induction of labour. Current guidelines support the use of doses that do not exceed 25 mcg in order to limit... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Misoprostol is a synthetic PGE analogue that is used for induction of labour. Current guidelines support the use of doses that do not exceed 25 mcg in order to limit maternal and neonatal adverse outcomes. The present meta-analysis investigates the efficacy and safety of oral compared to vaginally inserted misoprostol in terms of induction of labor and adverse peripartum outcomes.
METHODS
We searched Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar, and Clinicaltrials.gov databases from inception till April 2022. Randomized controlled trials that assessed the efficacy of oral misoprostol (per os or sublingual) compared to vaginally inserted misoprostol. Effect sizes were calculated in R. Sensitivity analysis was performed to evaluate the possibility of small study effects, p-hacking. Meta-regression and subgroup analysis according to the dose of misoprostol was also investigated. The methodological quality of the included studies was assessed by two independent reviewers using the risk of bias 2 tool. Quality of evidence for primary outcomes was evaluated under the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, ranging from very low to high.
RESULTS
Overall, 57 studies were included that involved 10,975 parturient. Their risk of bias ranged between low-moderate. There were no differences among the routes of intake in terms of successful vaginal delivery within 24 h (RR 0.90, 95% CI 0.80) and cesarean section rates (RR 0.92, 95% CI 0.82, 1.04). Sublingual misoprostol was superior compared to vaginal misoprostol in reducing the interval from induction to delivery (MD - 1.11 h, 95% CI - 2.06, - 0.17). On the other hand, per os misoprostol was inferior compared to vaginal misoprostol in terms of this outcome (MD 3.45 h, 95% CI 1.85, 5.06). Maternal and neonatal morbidity was not affected by the route or dose of misoprostol.
CONCLUSION
The findings of our study suggest that oral misoprostol intake is equally safe to vaginal misoprostol in terms of inducing labor at term. Sublingual intake seems to outperform the per os and vaginal routes without increasing the accompanying morbidity. Increasing the dose of misoprostol does not seem to increase its efficacy.
CLINICAL TRIAL REGISTRATION
Open Science Framework ( https://doi.org/10.17605/OSF.IO/V9JHF ).
Topics: Infant, Newborn; Pregnancy; Humans; Female; Misoprostol; Oxytocics; Cesarean Section; Labor, Induced; Administration, Sublingual
PubMed: 36472645
DOI: 10.1007/s00404-022-06867-9 -
BMJ (Clinical Research Ed.) Jul 2015
Review
Topics: Developing Countries; Evidence-Based Medicine; Female; Health Resources; Humans; Labor Stage, Third; Oxytocics; Postpartum Hemorrhage; Practice Guidelines as Topic; Pregnancy; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 26156874
DOI: 10.1136/bmj.h3251 -
Midwifery Sep 2014to identify primary and secondary outcome measures in randomised trials, and systematic reviews of randomised trials, measuring effectiveness of oxytocin for treatment... (Review)
Review
OBJECTIVES
to identify primary and secondary outcome measures in randomised trials, and systematic reviews of randomised trials, measuring effectiveness of oxytocin for treatment of delay in the first and second stages of labour, and to identify any positive health-focussed outcomes used.
DESIGN
eight relevant citation databases were searched up to January 2013 for all randomised trials, and systematic reviews of randomised trials, measuring effectiveness of oxytocin for treatment of delay in labour. Trials of active management of labour or partogram action lines were excluded. 1918 citations were identified. Two reviewers reviewed all citations and extracted data. Twenty-six individual trials and five systematic reviews were included. Primary and secondary outcome measures were documented and analysed using frequency distributions.
FINDINGS
most frequent primary outcomes were caesarean section (n=15, 46%), length of labour (n=14, 42%), measurements of uterine activity (n=13, 39%) and mode of vaginal birth (n=9, 27%). Maternal satisfaction was identified a priori by one review and included as a secondary outcome by three papers. No further positive health-focussed outcomes were identified.
KEY CONCLUSIONS
outcomes used to measure the effectiveness of oxytocin for treatment of delay in labour are heterogeneous and tend to focus on adverse events.
IMPLICATIONS FOR PRACTICE
it is recommended that, in future randomised trials of oxytocin use for delay in labour, some women-centred and health-focussed outcome measures should be used, which may instil a more salutogenic culture in childbirth.
Topics: Cesarean Section; Delivery, Obstetric; Female; Humans; Obstetric Labor Complications; Oxytocics; Oxytocin; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25017174
DOI: 10.1016/j.midw.2014.06.005 -
BMC Pregnancy and Childbirth Oct 2022This study aims to evaluate the efficacy and safety of the modified application of COOK Cervical Ripening Balloon (CCRB) for induction of labor (IOL) at term in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study aims to evaluate the efficacy and safety of the modified application of COOK Cervical Ripening Balloon (CCRB) for induction of labor (IOL) at term in primipara.
METHODS
A total of 227 singleton full-term pregnancies with indications of IOL were enrolled and randomly divided into the control and study groups in our hospital from January 2021 to December 2021. In the control group, a conventional method was used. Both the uterine and vaginal balloons were filled to 80 mL and removed after 12 h. In the study group, a modified method was used. The uterine and vaginal balloons were filled to 120 mL and 40 mL respectively. Light traction was given to help CCRB to be discharged after 12 h placement. Oxytocin was administered in both groups after CCRB was discharged before labor starting. The improved Bishop scores, duration of labor, and spontaneous delivery rate were evaluated in the two groups.
RESULTS
The improved Bishop scores in the study group were 3.06 ± 0.97 at 12 h placement of CCRB and 4.37 ± 0.87 when CCRB was discharged, which were significantly higher compared to the control group (2.52 ± 0.79, p < 0.05). Duration of the first stage of labor and the full labor in the study group were significantly shorter than those in the control group ((6.17 ± 2.85) h vs. (7.27 ± 2.90) h, p = 0.010; (7.07 ± 3.18) h vs. (8.09 ± 3.11) h, p = 0.028). No difference in spontaneous delivery rate between the two groups was observed. But the delivery rate within 24 h between the two groups was significantly different (79.79% vs. 55.91%, p < 0.05). For the cases with initial Bishop scores ≤ 3, the improved score was significantly increased, the first stage of labor and the full labor were significantly shorter in the study group than those in the control group (p < 0.05). Those results were not observed in cases with initial Bishop scores of 4-6.
CONCLUSIONS
The modified application of CCRB could benefit cervical ripening, shorten the duration of labor, especially for cases with poor cervical maturity, and improve the delivery rate within 24 h.
TRIAL REGISTRATION
Retrospectively registered: ChiCTR2200058270. Registered 04/04/2022.
Topics: Catheterization; Cervical Ripening; Cervix Uteri; Female; Humans; Labor, Induced; Oxytocics; Oxytocin; Pregnancy
PubMed: 36184583
DOI: 10.1186/s12884-022-05035-w