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American Family Physician Jun 2021
Review
Topics: Female; Humans; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Treatment Outcome
PubMed: 34060793
DOI: No ID Found -
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 -
Journal of Obstetric, Gynecologic, and... Sep 2020Cervical ripening and induction and augmentation of labor are common procedures in labor and birth units. The potential risks and benefits for the procedure should be...
Cervical ripening and induction and augmentation of labor are common procedures in labor and birth units. The potential risks and benefits for the procedure should be explained to women so that they can make informed decisions. Clinicians should be knowledgeable about the methods and medications used and be skilled in maternal-fetal assessment. Adequate nurse staffing is required to monitor the mother and fetus to promote the best possible outcomes. This practice monograph includes information on mechanical and pharmacologic methods for cervical ripening; labor induction and augmentation with oxytocin, a high alert drug; and nurse staffing levels and skills needed to provide safe and effective care during cervical ripening and labor induction and augmentation.
Topics: Adult; Cervical Ripening; Female; Humans; Labor, Induced; Obstetric Nursing; Oxytocics; Pregnancy; Textbooks as Topic
PubMed: 32778361
DOI: 10.1016/j.jogn.2020.04.005 -
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 -
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 -
International Journal of Gynaecology... Jun 2015The effectiveness of Foley catheter plus misoprostol for cervical ripening has not been convincingly shown in trials. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
The effectiveness of Foley catheter plus misoprostol for cervical ripening has not been convincingly shown in trials.
OBJECTIVES
To summarize the evidence comparing Foley catheter plus misoprostol versus misoprostol alone for cervical ripening.
SEARCH STRATEGY
Embase, Medline, and Cochrane Collaboration databases were searched with the terms "Foley catheter," "misoprostol," "cervical ripening," and "labor induction."
SELECTION CRITERIA
Randomized controlled trials comparing the methods of cervical ripening for delivery of a viable fetus were included.
DATA COLLECTION AND ANALYSIS
Study characteristics, quality, and outcomes were recorded. Random-effects models were used to combine data.
MAIN RESULTS
Eight trials were included, with 1153 patients overall. In a pooled analysis of seven high-quality studies, the combination group had a decreased time to delivery (mean difference -2.36 hours, 95% confidence interval [CI] -4.07 to -0.66; P=0.007). Risk of chorioamnionitis was significantly increased in the combination group (risk ratio [RR] 2.07, 95% CI 1.04-4.13; P=0.04), and that of tachysystole with fetal heart rate changes was decreased (RR 0.58, 95% CI 0.38-0.91; P=0.02). Frequency of cesarean did not differ (P=0.77).
CONCLUSIONS
The combined use of Foley catheter and misoprostol results in a reduced time to delivery, a reduced frequency tachysystole with fetal heart rate changes, and an increased incidence of chorioamnionitis.
Topics: Cervical Ripening; Chorioamnionitis; Delivery, Obstetric; Female; Humans; Misoprostol; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic; Time Factors; Urinary Catheterization
PubMed: 25794821
DOI: 10.1016/j.ijgo.2015.01.005 -
Obstetrics and Gynecology Feb 2023Despite lack of evidence for a safety threshold for oxytocin dose rate, many hospital protocols specify a maximum rate. We investigated whether exceeding 20... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Despite lack of evidence for a safety threshold for oxytocin dose rate, many hospital protocols specify a maximum rate. We investigated whether exceeding 20 milliunits/min of oxytocin was associated with adverse outcomes.
METHODS
This is a secondary analysis of a double-blind, single-center, randomized controlled trial of nulliparous patients with singleton gestations at 36 weeks of gestation or later who presented in spontaneous labor randomized 1:1 to either a high-dose oxytocin titration regimen (initial-incremental rate of 6 milliunits/min) or standard-dose titration regimen (initial-incremental rate of 2 milliunits/min) for labor augmentation. A maximum oxytocin dose rate limit was not specified in the study protocol. For this secondary analysis, outcomes of participants who received oxytocin and exceeded a dose rate of 20 milliunits/min at any point in labor were compared with those whose rate remained at 20 milliunits/min or less. In addition, the cumulative proportions of labor and birth outcomes were calculated for each maximum dose rate of oxytocin reached among this study cohort.
RESULTS
Of the 1,003 participants in the parent trial, 955 (95.2%) received oxytocin, as planned, and were included, with 190 (19.9%) exceeding a maximum dose rate of 20 milliunits/min. Those who exceeded 20 milliunits/min were older and were more likely to have rupture of membranes as their trial entry indication, have hypertensive disorders of pregnancy, receive intrapartum magnesium sulfate infusion, and receive oxytocin for longer. Those whose maximum rates exceeded 20 milliunits/min underwent cesarean delivery more frequently, but the majority (74%) still delivered vaginally. In multivariable analyses, there were no significant associations between maximum oxytocin dose rates greater than 20 milliunits/min and cesarean delivery (adjusted odds ratio [aOR] 1.57, 95% CI 1.00-2.46), peripartum infection (aOR 0.69, 95% CI 0.41-1.19), postpartum hemorrhage (aOR 1.37, 95% CI 0.70-2.71), or neonatal intensive care unit (NICU) admission (aOR 1.72, 95% CI 0.89-3.31). Although 85% of spontaneous vaginal deliveries occurred at maximum oxytocin dose rates of 20 milliunits/min or less, vaginal deliveries continued to occur at higher maximum dose rates. The cumulative proportions of NICU admissions and composite severe neonatal morbidity and mortality cases increased with increasing oxytocin dose rates even with maximum oxytocin dose rates at 20 milliunits/min or less.
CONCLUSION
In multivariable analyses, there are no significant differences in maternal or perinatal adverse outcomes based on exceeding 20 milliunits/min of oxytocin. These data suggest that oxytocin dosing should be individualized to each patient and not be based on arbitrary thresholds.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov , NCT02487797.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cesarean Section; Delivery, Obstetric; Labor, Induced; Oxytocics; Oxytocin; Double-Blind Method
PubMed: 36649339
DOI: 10.1097/AOG.0000000000005058 -
Archives of Gynecology and Obstetrics Mar 2020Clinical studies and trials have shown that oxytocin can effectively reduce postpartum bleeding, whether by intramuscular (IM) injection or intravenous (IV) injection.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical studies and trials have shown that oxytocin can effectively reduce postpartum bleeding, whether by intramuscular (IM) injection or intravenous (IV) injection. These two methods are widely used in the prevention and treatment for the third stage of childbirth. However, it is unclear whether the subtle differences between the mode of these routes have any effect on maternal outcomes.
OBJECTIVES
To systematically evaluate the efficacy and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labor after vaginal birth.
METHODS
Computerized retrieval of PubMed, the Cochrane Library, Web of Science, Embase, and ClinicalTrials.gov was conducted to collect randomized controlled trials (RCT) on the effects of IM and IV oxytocin on the third stage of labor. After independent literature screening, data extraction and evaluation of the bias risk of included studies by two evaluators, RevMan 5.3 software was used for a meta-analysis.
RESULTS
Six studies with 7734 women were included in this study. Meta-analysis results showed that: the severe postpartum hemorrhage (PPH) rate [risk ratio (RR) 1.54, 95% confidence interval (95% CI) 1.08-2.20, P = 0.02], PPH rate (RR 1.31, 95% CI 1.11-1.55, P = 0.001), incidence of blood transfusion (RR 2.30, 95% CI 1.35-3.93, P = 0.002) and the need of manual removal of placenta (RR 1.44, 95% CI 1.05-1.96, P = 0.02) for IM group were higher than IV group, but there were no significant differences in the use of additional uterotonics (P = 0.31) and the incidence of serious maternal morbidity and adverse effects between two groups. None of the included studies reported maternal death.
CONCLUSION
For clinical practice, intravenous injection oxytocin 10 IU may be a good, safe option in the management of the third stage of labor. Medical conditions, available resources, adverse effects, and women' s preferences should also be considered. If an IV line is already in place at delivery, IV administration may be preferable to IM injection.
Topics: Administration, Intravenous; Adolescent; Adult; Female; Humans; Injections, Intramuscular; Labor Stage, Third; Middle Aged; Oxytocics; Oxytocin; Pregnancy; Young Adult
PubMed: 32124015
DOI: 10.1007/s00404-020-05467-9 -
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