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Petrecca A, Saccone G, Berghella V. Nitroglycerine for retained placenta: a meta-analysis of randomized controlled trials. Am J Obstet Gynecol MFM 2025; 7:101605. [PMID: 39818273 DOI: 10.1016/j.ajogmf.2025.101605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 11/24/2024] [Indexed: 01/18/2025]
Abstract
OBJECTIVE To evaluate the effect of nitroglycerine on placenta delivery after retained placenta. DESIGN Systematic review with meta-analysis. DATA SOURCES MEDLINE, PROSPERO, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library, Scielo were searched from their inception until February 2024. ELIGIBILITY CRITERIA FOR SELECTING STUDIES We included all randomized clinical trials comparing use of nitroglycerine (i.e. intervention group) with placebo or with no treatment (i.e. control group) given for retained placenta after vaginal delivery. DATA SYNTHESIS The primary outcome was rate of manual removal of the placenta. The summary measures were reported as relative risk (RR) or as mean difference (MD) with 95% of confidence interval (CI). RESULTS Four trials, including 1,279 pregnancies, were analyzed. The quality of the RCTs included was moderate. Pooled results showed that administration of nitroglycerine in women with retained placenta after vaginal delivery was associated with similar incidence of manual removal compared to control (89% vs 90%; RR 0.94, 95% CI 0.74 to 1.20). We also found similar mean postpartum blood loss, and no significant differences in the incidence of drop of hb > 15 or 30%, need for uterotonics. CONCLUSIONS Use of nitroglycerine in women with retained placenta after vaginal delivery did not reduce the use of manual removal of the placenta.
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Affiliation(s)
- Alessandro Petrecca
- Department of Women's, Child and Public Health Sciences, UOC Gynecology Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy (Dr Petrecca)
| | - Gabriele Saccone
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy (Dr Saccone)
| | - Vincenzo Berghella
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA (Dr Berghella).
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Patrick HS, Mitra A, Rosen T, Ananth CV, Schuster M. Pharmacologic intervention for the management of retained placenta: a systematic review and meta-analysis of randomized trials. Am J Obstet Gynecol 2020; 223:447.e1-447.e19. [PMID: 32592695 DOI: 10.1016/j.ajog.2020.06.044] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/10/2020] [Accepted: 06/22/2020] [Indexed: 01/26/2023]
Abstract
BACKGROUND Retained placenta affects 2% to 3.3% of all vaginal deliveries and is one of the leading causes of postpartum hemorrhage worldwide. Despite the prevalence of this condition, there is limited guidance on its management. OBJECTIVE A systematic review and meta-analysis were performed to evaluate the efficacy of pharmacologic interventions for the management of retained placenta. STUDY DESIGN PubMed, ClinicalTrials.gov, Cochrane Library, Web of Science, and Scopus were searched for full-text publications in English. Search terms included "retained placenta" AND "treatment" OR "therapy" OR "disease management" OR "Pitocin" OR "misoprostol" OR "Cytotec" OR "dinoprostone" OR "nitroglycerin" OR "carbetocin" OR "ergotamine," with no restriction on publication dates. Only randomized controlled trials were included. The primary outcome was the need for manual extraction of the placenta or dilation and curettage. Reviewers evaluated the quality of included articles using the Cochrane Collaboration's tool for assessing the risk of bias. Pooled risk ratios were estimated based on random- and fixed-effects analyses. Interstudy heterogeneity was considered when I2≥50%. RESULTS The literature search identified 29 randomized controlled trials that met the inclusion criteria (2682 subjects). The most commonly used agent across the studies was oxytocin administered via umbilical vein injection; there was high heterogeneity among these studies (I2=62%). Oxytocin was inferior to carbetocin (risk ratio, 1.61; 95% confidence interval, 1.03-2.52) and prostaglandins (risk ratio, 2.63; 95% confidence interval, 1.18-5.86) for the primary outcome. For oxytocin, prostaglandin agents, and nitroglycerin, there was a trend toward favoring the study drug for the primary outcome compared with control or placebo. Compared with placebo or control, estimated blood loss was lower if pharmacologic interventions were administered, with a mean difference of 121.5 mL (95% confidence interval, -185.7 to -52.3). There was no difference in postpartum hemorrhage or the need for blood transfusion between pharmacologic interventions and placebo or control. CONCLUSION Pooled estimates for oxytocin via umbilical vein injection, prostaglandin agents, and nitroglycerin performed favorably compared with placebo or control for the management of retained placenta. Carbetocin and prostaglandin agents were superior to oxytocin in reducing the need for manual extraction or dilation and curettage.
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Khanna K, Karwasra R, Choudhary S, Sharma D, Sharma N, Nagpal P, Chorsiya V, Nishad DK, Popli H, Bhatnagar A. Submental nalbuphine exhibits improved efficacy in ameliorating acute pain in prehospital emergent conditions; a comparative study with conventional intramuscular using gamma scintigraphy. Injury 2020; 51:1970-1978. [PMID: 32591214 DOI: 10.1016/j.injury.2020.06.031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 06/13/2020] [Accepted: 06/19/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND Nalbuphine (NLB) is a kappa-agonist and mu-partial antagonist, widely used for opioid withdrawal de-addiction, opioid-induced pruritis and as emergent analgesia. OBJECTIVE The present study aimed to assess the safety and efficacy of NLB in pain sensitization, through a submental route so as to provide faster management in emergent situations. MATERIALS & METHODS In-vivo efficacy and safety studies of NLB-submental injection were assessed in Sprague-Dawley(SD) rats. For eddy's hot plate study, animals were allocated into three groups, the first group served as normal control; group II received NLB (through submental route at 1.2 mg/kg); group III received NLB (through intramuscular route at 1.2 mg/kg). Response latency (in terms of response latency) was measured at 10, 30 & 60 min in all the experimental groups. Safety studies were carried out according to OECD 423. In-vitro release study was conducted using a cellulose dialysis membrane (12,000 KDa). The biodistribution and release kinetics studies were carried out using gamma scintigraphy studies in New Zealand rabbits and humans respectively. RESULTS The response latency of NLB from the submental route was found to be 7.17 (SD 1.47) seconds and in the case of the intramuscular route it was calculated as 4.00 (SD 1.26) seconds at 10 min. The data depicts the better efficacy of submental injection in ameliorating pain than the intramuscular injection. Toxicity studies predict the safe profile through a submental route. The release kinetics in humans of submental NLB was 46% faster as compared to the intramuscular site of injection. The NLB injection through both routes was compared by non-invasive gamma scintigraphy technique and we found that submental injection has faster (within 10 min) onset of action & distributes rapidly. CONCLUSION The submental route of NLB is faster, more efficacious than the intramuscular route. Thus, we conclude that in the case of emergent scenarios (i.v or i.m. route is compromised), where immediate relief is necessary, the submental route is a preferred choice.
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Affiliation(s)
- Kushagra Khanna
- Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA; Department of Pharmacy, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, INDIA
| | - Ritu Karwasra
- Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA
| | - Sandeep Choudhary
- Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA
| | - Deeksha Sharma
- Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA
| | - Nitin Sharma
- Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH-58, Baghpat Crossing, Bypass Road, Meerut, 250005, INDIA
| | - Puja Nagpal
- Department of Research and Education, Indian Spinal Injuries Centre, INDIA
| | - Varsha Chorsiya
- School of Physiotherapy, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, INDIA
| | - Dhruv Kumar Nishad
- Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA
| | - Harvinder Popli
- Department of Pharmacy, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, INDIA.
| | - Aseem Bhatnagar
- Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA.
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Ma Y, You Y, Jiang X, Lin X. Use of nitroglycerin for parallel transverse uterine cesarean section in patients with pernicious placenta previa and placenta accrete and predicted difficult airway: A case report and review of literature. Medicine (Baltimore) 2020; 99:e18943. [PMID: 32000415 PMCID: PMC7004715 DOI: 10.1097/md.0000000000018943] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
RATIONALE The incidence of obstetric hemorrhage due to pernicious placenta previa (PPP) and placenta accreta is currently increasing in China. Parallel transverse uterine incision (PTUI) cesarean section (CS) is a novel technique designed to avoid transecting the placenta and control postpartum hemorrhage during CS in these patients in our hospital. A key point of anesthesia management related to PTUI CS involves keeping the uterus relaxed. General anesthesia (GA) has often been performed, and inhaled volatile anesthetics have traditionally been recommended for this purpose; however, GA may be contraindicated in patients with difficult airways. PATIENT CONCERNS The patient was predicted to have a difficult airway, and GA may have resulted in potentially life-threatening complications. An alternative and safer method of achieving uterine relaxation during PTUI CS was thus required. DIAGNOSES The patient was diagnosed with PPP, and a predicted difficult airway was suspected preoperatively. INTERVENTIONS PTUI CS was planned to control postpartum hemorrhage and preserve fertility during CS. Uterine relaxation during PTUI CS was achieved with intravenous nitroglycerin under combined spinal-epidural anesthesia. OUTCOME Intravenous nitroglycerin and combined spinal-epidural anesthesia achieved uterine relaxation during the time from delivery of the neonate to making the second transverse incision in the lower segment of the uterus during PTUI CS. Both the parturient and neonate were well and were discharged 4 days later. LESSIONS Intravenous nitroglycerin and combined spinal-epidural anesthesia may offer an alternative to GA for achieving uterine relaxation in patients with PPP and a predicted difficult airway undergoing PTUI CS to control postpartum hemorrhage.
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Affiliation(s)
- Yushan Ma
- Department of Anesthesiology, West China Second University Hospital, Sichuan University
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education
| | - Yong You
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaoqin Jiang
- Department of Anesthesiology, West China Second University Hospital, Sichuan University
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education
| | - Xuemei Lin
- Department of Anesthesiology, West China Second University Hospital, Sichuan University
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education
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Denison FC, Carruthers KF, Hudson J, McPherson G, Scotland G, Brook-Smith S, Clarkson C, Peace M, Brewin J, Chua GN, Hallowell N, Norman JE, Lawton J, Norrie J. Glyceryl trinitrate to reduce the need for manual removal of retained placenta following vaginal delivery: the GOT-IT RCT. Health Technol Assess 2019; 23:1-72. [PMID: 31912780 PMCID: PMC6970217 DOI: 10.3310/hta23700] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Retained placenta is associated with postpartum haemorrhage and can lead to significant maternal morbidity if untreated. The only effective treatment is the surgical procedure of manual removal of placenta, which is costly, requires skilled staff, requires an operative environment and is unpleasant for women. Small studies suggest that glyceryl trinitrate may be an effective medical alternative. OBJECTIVE To determine the clinical effectiveness and cost-effectiveness of sublingual glyceryl trinitrate spray compared with placebo in reducing the need for manual removal of placenta in women with retained placenta after vaginal delivery following the failure of current management. DESIGN A group-sequential randomised double-blind placebo-controlled trial with a cost-effectiveness analysis. SETTING There were 29 obstetric units in the UK involved in the study. PARTICIPANTS There were 1107 women (glyceryl trinitrate group, n = 543; placebo group, n = 564) randomised between October 2014 and July 2017. INTERVENTIONS Glyceryl trinitrate spray was administered to 541 women in the intervention group, and a placebo was administered to 563 women in the control group. MAIN OUTCOME MEASURES Four primary outcomes were defined: (1) clinical - the need for manual removal of placenta, (2) safety - measured blood loss, (3) patient sided - satisfaction with treatment and side effects and (4) economic - cost-effectiveness of both treatments using the UK NHS perspective. Secondary clinical outcomes included a > 15% decrease in haemoglobin level, time from randomisation to delivery of placenta in theatre, the need for earlier manual removal of placenta than planned, increase in heart rate or decrease in blood pressure, requirement for blood transfusion, requirement for general anaesthesia, maternal pyrexia, and sustained uterine relaxation requiring additional uterotonics. RESULTS No difference was observed between the glyceryl trinitrate group and the control group for the placenta remaining undelivered within 15 minutes of study treatment (93.3% vs. 92%; odds ratio 1.01, 95% confidence interval 0.98 to 1.04; p = 0.393). There was no difference in blood loss of > 1000 ml between the glyceryl trinitrate group and the control group (22.2% vs. 15.5%; odds ratio 1.14, 95% confidence interval 0.88 to 1.48; p = 0.314). Palpitations were more common in the glyceryl trinitrate group than in the control group after taking the study drug (9.8% vs. 4.0%; odds ratio 2.60, 95% confidence interval 1.40 to 4.84; p = 0.003). There was no difference in any other measures of patient satisfaction between the groups. There was no difference in costs to the health service between groups (mean difference £55.30, 95% confidence interval -£199.20 to £309.79). Secondary outcomes revealed that a fall in systolic or diastolic blood pressure, or an increase in heart rate, was more common in the glyceryl trinitrate group than in the control group (odds ratio 4.9, 95% confidence interval 3.7 to 6.4; p < 0.001). The need for a blood transfusion was also more common in the glyceryl trinitrate group than in the control group (odds ratio 1.53, 95% confidence interval 1.04 to 2.25; p = 0.033). CONCLUSIONS Glyceryl trinitrate spray did not increase the delivery of retained placenta within 15 minutes of administration when compared with the placebo, and was not cost-effective for medical management of retained placenta. More participants reported palpitations and required a blood transfusion in the glyceryl trinitrate group. Further research into alternative methods of medical management of retained placenta is required. TRIAL REGISTRATION Current Controlled Trials ISRCTN88609453. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 70. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Fiona C Denison
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Kathryn F Carruthers
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Jemma Hudson
- Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | - Gladys McPherson
- Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | - Graham Scotland
- Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - Sheonagh Brook-Smith
- Simpson's Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Cynthia Clarkson
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Mathilde Peace
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | | | - Gin Nie Chua
- Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - Nina Hallowell
- Ethox Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Jane E Norman
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Julia Lawton
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - John Norrie
- Edinburgh Clinical Trials Unit/Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
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Denison FC, Carruthers KF, Hudson J, McPherson G, Chua GN, Peace M, Brewin J, Hallowell N, Scotland G, Lawton J, Norrie J, Norman JE, GOT-IT investigator team. Nitroglycerin for treatment of retained placenta: A randomised, placebo-controlled, multicentre, double-blind trial in the UK. PLoS Med 2019; 16:e1003001. [PMID: 31887169 PMCID: PMC6936786 DOI: 10.1371/journal.pmed.1003001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 11/22/2019] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Retained placenta following vaginal delivery is a major cause of postpartum haemorrhage. Currently, the only effective treatments for a retained placenta are the surgical procedures of manual removal of placenta (MROP) and uterine curettage, which are not universally available, particularly in low- and middle-income countries. The objective of the trial was to determine whether sublingual nitroglycerin spray was clinically effective and cost-effective for medical treatment of retained placenta following vaginal delivery. METHODS AND FINDINGS A randomised, placebo-controlled, double-blind trial was undertaken between October 2014 and July 2017 at 29 delivery units in the UK (Edinburgh, Glasgow, Manchester, Newcastle, Preston, Warrington, Chesterfield, Crewe, Durham, West Middlesex, Aylesbury, Furness, Southampton, Bolton, Sunderland, Oxford, Nottingham [2 units], Burnley, Chertsey, Stockton-on-Tees, Middlesborough, Chester, Darlington, York, Reading, Milton Keynes, Telford, Frimley). In total, 1,107 women with retained placenta following vaginal delivery were recruited. The intervention was self-administered 2 puffs of sublingual nitroglycerin (800 μg; intervention, N = 543) or placebo spray (control, N = 564). The primary clinical outcome was the need for MROP, assessed at 15 minutes following administration of the intervention. Analysis was based on the intention-to-treat principle. The primary safety outcome was measured blood loss between study drug administration and transfer to the postnatal ward or other clinical area. The primary patient-sided outcomes were satisfaction with treatment and side-effect profile, assessed by questionnaires pre-discharge and 6 weeks post-delivery. Secondary clinical outcomes were measured at 5 and 15 minutes after study drug administration and prior to hospital discharge. There was no statistically significant or clinically meaningful difference in need for MROP by 15 minutes (primary clinical outcome, 505 [93.3%] for nitroglycerin versus 518 [92.0%] for placebo, odds ratio [OR] 1.01 [95% CI 0.98-1.04], p = 0.393) or blood loss (<500 ml: nitroglycerin, 238 [44.3%], versus placebo, 249 [44.5%]; 500 ml-1,000 ml: nitroglycerin, 180 [33.5%], versus placebo, 224 [40.0%]; >1,000 ml: nitroglycerin, 119 [22.2%], versus placebo, 87 [15.5%]; ordinal OR 1.14 [95% CI 0.88-1.48], p = 0.314) or satisfaction with treatment (nitroglycerin, 288 [75.4%], versus placebo, 303 [78.1%]; OR 0.87 [95% CI 0.62-1.22], p = 0.411) or health service costs (mean difference [£] 55.3 [95% CI -199.20 to 309.79]). Palpitations following drug administration were reported more often in the nitroglycerin group (36 [9.8%] versus 15 [4.0%], OR 2.60 [95% CI 1.40-4.84], p = 0.003). There were 52 serious adverse events during the trial, with no statistically significant difference in likelihood between groups (nitroglycerin, 27 [5.0%], versus placebo, 26 [4.6%]; OR 1.13 [95% CI 0.54-2.38], p = 0.747). The main limitation of our study was the low return rate for the 6-week postnatal questionnaire. There were, however, no differences in questionnaire return rates between study groups or between women who did and did not have MROP, with the patient-reported use of outpatient and primary care services at 6 weeks accounting for only a small proportion (approximately 5%) of overall health service costs. CONCLUSIONS In this study, we found that nitroglycerin is neither clinically effective nor cost-effective as a medical treatment for retained placenta, and has increased side effects, suggesting it should not be used. Further research is required to identify an effective medical treatment for retained placenta to reduce the morbidity caused by this condition, particularly in low- and middle-income countries where surgical management is not available. TRIAL REGISTRATION ISRCTN.com ISRCTN88609453 ClinicalTrials.gov NCT02085213.
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Affiliation(s)
- Fiona C. Denison
- Tommy’s Centre for Maternal and Fetal Health, Medical Research Council Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
- * E-mail:
| | - Kathryn F. Carruthers
- Tommy’s Centre for Maternal and Fetal Health, Medical Research Council Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Jemma Hudson
- Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom
| | - Gladys McPherson
- Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom
| | - Gin Nie Chua
- Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Mathilde Peace
- Tommy’s Centre for Maternal and Fetal Health, Medical Research Council Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | | | - Nina Hallowell
- Wellcome Centre for Ethics and Humanities, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
- Ethox Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Graham Scotland
- Centre for Healthcare Randomised Trials, Health Services Research Unit, University of Aberdeen, Aberdeen, United Kingdom
- Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Julia Lawton
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
| | - John Norrie
- Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
| | - Jane E. Norman
- Tommy’s Centre for Maternal and Fetal Health, Medical Research Council Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
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Denison FC, Norrie J, Lawton J, Norman JE, Scotland G, McPherson GC, McDonald A, Forrest M, Hudson J, Brewin J, Peace M, Clarkson C, Brook-Smith S, Morrow S, Hallowell N, Hodges L, Carruthers KF. A pragmatic group sequential, placebo-controlled, randomised trial to determine the effectiveness of glyceryl trinitrate for retained placenta (GOT-IT): a study protocol. BMJ Open 2017; 7:e017134. [PMID: 28928192 PMCID: PMC5623532 DOI: 10.1136/bmjopen-2017-017134] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 05/29/2017] [Accepted: 07/03/2017] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION A retained placenta is diagnosed when the placenta is not delivered following delivery of the baby. It is a major cause of postpartum haemorrhage and treated by the operative procedure of manual removal of placenta (MROP). METHODS AND ANALYSIS The aim of this pragmatic, randomised, placebo-controlled, double-blind UK-wide trial, with an internal pilot and nested qualitative research to adjust strategies to refine delivery of the main trial, is to determine whether sublingual glyceryl trinitrate (GTN) is (or is not) clinically and cost-effective for (medical) management of retained placenta. The primary clinical outcome is need for MROP, defined as the placenta remaining undelivered 15 min poststudy treatment and/or being required within 15 min of treatment due to safety concerns. The primary safety outcome is measured blood loss between administration of treatment and transfer to the postnatal ward or other clinical area. The primary patient-sided outcome is satisfaction with treatment and a side effect profile. The primary economic outcome is net incremental costs (or cost savings) to the National Health Service of using GTN versus standard practice. Secondary outcomes are being measured over a range of clinical and economic domains. The primary outcomes will be analysed using linear models appropriate to the distribution of each outcome. Health service costs will be compared with multiple trial outcomes in a cost-consequence analysis of GTN versus standard practice. ETHICS AND DISSEMINATION Ethical approval has been obtained from the North-East Newcastle & North Tyneside 2 Research Ethics Committee (13/NE/0339). Dissemination plans for the trial include the Health Technology Assessment Monograph, presentation at international scientific meetings and publication in high-impact, peer-reviewed journals. TRIAL REGISTRATION NUMBER ISCRTN88609453; Pre-results.
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Affiliation(s)
- Fiona C Denison
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - John Norrie
- The Centre for Healthcare Randomised Trials (CHaRT), Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | - Julia Lawton
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
| | - Jane E Norman
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Graham Scotland
- Health Economics Research Unit, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
| | - Gladys C McPherson
- The Centre for Healthcare Randomised Trials (CHaRT), Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | - Alison McDonald
- The Centre for Healthcare Randomised Trials (CHaRT), Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | - Mark Forrest
- The Centre for Healthcare Randomised Trials (CHaRT), Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | - Jemma Hudson
- The Centre for Healthcare Randomised Trials (CHaRT), Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | | | - Mathilde Peace
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Cynthia Clarkson
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Sheonagh Brook-Smith
- Simpson's Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Susan Morrow
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Nina Hallowell
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
- Ethox Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Laura Hodges
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Kathryn F Carruthers
- Tommy's Centre for Maternal and Fetal Health Research, Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
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Akol AD, Weeks AD. Retained placenta: will medical treatment ever be possible? Acta Obstet Gynecol Scand 2016; 95:501-4. [PMID: 26765548 PMCID: PMC4849196 DOI: 10.1111/aogs.12848] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Accepted: 12/23/2015] [Indexed: 11/28/2022]
Abstract
The standard treatment for retained placenta is manual removal whatever its subtype (adherens, trapped or partial accreta). Although medical treatment should reduce the risk of anesthetic and surgical complications, they have not been found to be effective. This may be due to the contrasting uterotonic needs of the different underlying pathologies. In placenta adherens, oxytocics have been used to contract the retro‐placental myometrium. However, if injected locally through the umbilical vein, they bypass the myometrium and perfuse directly into the venous system. Intravenous injection is an alternative but exacerbates a trapped placenta. Conversely, for trapped placentas, a relaxant could help by resolving cervical constriction, but would worsen the situation for placenta adherens. This confusion over medical treatment will continue unless we can find a way to diagnose the underlying pathology. This will allow us to stop treating the retained placenta as a single entity and to deliver targeted treatments.
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Affiliation(s)
- Achier D Akol
- Department of Women's and Children's Health, University of Liverpool, Liverpool, UK
| | - Andrew D Weeks
- Department of Women's and Children's Health, University of Liverpool, Liverpool, UK
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Abstract
Abstract
The American Society of Anesthesiologists Committee on Standards and Practice Parameters and the Task Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology present an updated report of the Practice Guidelines for Obstetric Anesthesia.
Supplemental Digital Content is available in the text.
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Kashanian M, Hasankhani S, Sheikhansari N, Bahasadri S, Homam H. The effects of sequential use of oxytocin and sublingual nitroglycerin in the cases of retained placenta. J Matern Fetal Neonatal Med 2015; 29:3254-9. [PMID: 26701364 DOI: 10.3109/14767058.2015.1124264] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To evaluate the effects of adding sublingual nitroglycerin to oxytocin, for delivery of retained placenta after vaginal delivery. METHOD The study was performed as a placebo controlled clinical trial on women who did not finish delivering placenta after 30 min of active management of the third stage of labor. In case group, 1 mg nitroglycerin and in the control group, placebo was prescribed sublingually. RESULTS In total, 80 women finished the study. The number of manual removal of placenta did not show significant difference between the two groups [25 women (62.5%) in the case and 30 women (75%) in the control group, p = 0.335]. There was no significant difference between the two groups according to duration of the third stage of labor, hemoglobin index, decline in HB index >30% and maternal vital signs after treatment. There was no significant difference between the two groups according to adverse effects [eight women (20%) in the case group and four (10%) in the control group (p = 0.348)]. CONCLUSION The sequential use of oxytocin and sublingual nitroglycerin could not lead to delivery of more placentas and did not reduce the necessity of manual removal of placenta in comparison with placebo.
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Affiliation(s)
- Maryam Kashanian
- a Department of Obstetrics and Gynecology , Akbarabadi Teaching Hospital, Iran University of Medical Sciences , Tehran , Iran and
| | - Samira Hasankhani
- a Department of Obstetrics and Gynecology , Akbarabadi Teaching Hospital, Iran University of Medical Sciences , Tehran , Iran and
| | | | - Shohreh Bahasadri
- a Department of Obstetrics and Gynecology , Akbarabadi Teaching Hospital, Iran University of Medical Sciences , Tehran , Iran and
| | - Homa Homam
- a Department of Obstetrics and Gynecology , Akbarabadi Teaching Hospital, Iran University of Medical Sciences , Tehran , Iran and
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Abdel‐Aleem H, Abdel‐Aleem MA, Shaaban OM, Cochrane Pregnancy and Childbirth Group. Nitroglycerin for management of retained placenta. Cochrane Database Syst Rev 2015; 2015:CD007708. [PMID: 26558329 PMCID: PMC8498020 DOI: 10.1002/14651858.cd007708.pub3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of nitroglycerin (NTG), either alone or in combination with uterotonics, may be of value to minimise the need for manual removal of the placenta in theatre under anaesthesia. OBJECTIVES To evaluate the benefits and harms of NTG as a tocolytic, either alone or in addition to uterotonics, in the management of retained placenta. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2015), reference lists of retrieved studies and contacted experts in the field. SELECTION CRITERIA Any adequately randomised controlled trial (RCT) comparing the use of NTG, either alone or in combination with uterotonics, with no intervention or with other interventions in the management of retained placenta. All women having a vaginal delivery with a retained placenta, regardless of the management of the third stage of labour (expectant or active). We included all trials with haemodynamically stable women in whom the placenta was not delivered at least within 15 minutes after delivery of the baby. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS We included three randomised controlled trials (RCTs) with 175 women. The three published RCTs compared NTG alone versus placebo. The detachment status of retained placenta was unknown in all three RCTs. Collectively, among the three included trials, two were judged to be at low risk of bias and the third trial was judged to be at high risk of bias for two domains: incomplete outcome data and selective reporting. The three trials reported seven out of 23 of the review's pre-specified outcomes.The primary outcome "manual removal of the placenta" was reported in all three studies. No differences were seen between NTG and placebo for manual removal of the placenta (average risk ratio (RR) 0.83, 95% confidence interval (CI) 0.47 to 1.46; women = 175; I² = 81%). A random-effects model was used because of evidence of substantial heterogeneity in the analysis. There were also no differences between groups for risk of severe postpartum haemorrhage (RR 0.93, 95% CI 0.62 to 1.39; women = 150; studies = two; I² = 0%). Blood transfusion was only reported in one study (40 women) and again there was no difference between groups (RR 1.00, 95% CI 0.07 to 14.90; women = 40; I² = 0%). Mean blood loss (mL) was reported in the three studies and no differences were observed (mean difference (MD) -115.31, 95% CI -306.25 to 75.63; women = 169; I² = 83%). Nitroglycerin administration was not associated with an increase in headaches (RR 1.09, 95% CI 0.80 to 1.47; women = 174; studies = three; I² = 0%). However, nitroglycerin administration was associated with a significant, though mild, decrease in systolic and diastolic blood pressure and a significant increase in pulse rate (MD -3.75, 95% CI -7.47 to -0.03) for systolic blood pressure, and (MD 6.00, 95% CI 3.07 to 8.93) for pulse rate (beats per minute) respectively (reported by only one study including 24 participants). Maternal mortality and addition of therapeutic uterotonics were not reported in any study. AUTHORS' CONCLUSIONS In cases of retained placenta, currently available data showed that the use of NTG alone did not reduce the need for manual removal of placenta. This intervention did not increase the incidence of severe postpartum haemorrhage nor the need for blood transfusion. Haemodynamically, NTG had a significant though mild effect on both pulse rate and blood pressure.
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Affiliation(s)
- Hany Abdel‐Aleem
- Assiut University HospitalDepartment of Obstetrics and Gynecology, Faculty of MedicineAssiutAssiutEgypt71511
| | - Mahmoud A Abdel‐Aleem
- Assiut University HospitalDepartment of Obstetrics and Gynecology, Faculty of MedicineAssiutAssiutEgypt71511
| | - Omar M Shaaban
- Assiut University HospitalDepartment of Obstetrics and Gynecology, Faculty of MedicineAssiutAssiutEgypt71511
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Pharmacologic intervention for retained placenta: a systematic review and meta-analysis. Obstet Gynecol 2015; 125:711-718. [PMID: 25730236 DOI: 10.1097/aog.0000000000000697] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To assess the effectiveness and safety of pharmacologic interventions for the treatment of retained placenta (when the placenta remains undelivered after 30 minutes of active management of the third stage of labor). DATA SOURCES We searched: 1) Cochrane Central Register of Controlled Trials (CENTRAL), 2) Cochrane Pregnancy and Childbirth Group's Trials Register, 3) EMBASE, and 4) MEDLINE from inception to June 2014. METHODS OF STUDY SELECTION Randomized controlled trials comparing a pharmacologic intervention(s) with a placebo for the treatment of retained placenta were included. TABULATION, INTEGRATION, AND RESULTS Sixteen randomized controlled trials, including 1,683 participants, were included. Study characteristics and quality were recorded. The meta-analysis was based on random-effects methods for pooled data. There were no statistically significant differences in the requirement to perform manual removal of a placenta in patients treated with oxytocin (55% compared with 60%; relative risk [RR] 0.86, 95% confidence interval [CI] 0.73-1.02; 10 randomized controlled trials [RCTs]), prostaglandins (44% compared with 55%; RR 0.82, 95% CI 0.58-1.15; four RCTs), nitroglycerin (85% compared with 80%; RR 1.06, 95% CI 0.80-1.41; one RCT), or oxytocin and nitroglycerin (52% compared with 79%; RR 0.23, 95% CI 0.01-8.48; two RCTs) compared with placebo. There was limited reporting of secondary outcomes. CONCLUSION As opposed to the use of oxytocin as part of the active management of the third stage of labor that has been shown to diminish bleeding in the third stage, once the diagnosis of retained placenta has been made, no pharmacologic treatment has been shown to be effective. When retained placenta is diagnosed, immediate manual removal of the placenta should be considered. SYSTEMATIC REVIEW REGISTRATION PROSPERO International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42014010641.
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Lim PS, Ismail NAM, Ghani NAA, Kampan NC, Sulaiman AS, Ng BK, Chew KT, Karim AKA, Yassin MAJM. Retained placenta: Do we have any option? World J Obstet Gynecol 2014; 3:124-129. [DOI: 10.5317/wjog.v3.i3.124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 06/06/2014] [Accepted: 07/14/2014] [Indexed: 02/05/2023] Open
Abstract
Retained placenta is a known cause of post-partum haemorrhage and maternal mortality. A recent systemic review has confirmed that the incidence of retained placenta had increased all over the world, which is more common in developed countries. Failure of retro-placental myometrium contraction is the main cause of retained placenta. Maternal age greater than 35 years, grandmultipara, preterm labor, history of previous retained placenta, and caesarean section were the risk factors for retained placenta. Manual removal of the placenta has been the treatment of choice. Attempts had been made by clinician and researchers to find a safe, effective and reliable method to avoid the need for surgical intervention. The efficacy and safety of prostaglandin, nitroglycerin or acupuncture in the management of retained placenta are yet to be further evaluated. Nonetheless, till date only intra-umbilical vein oxytocin has been studied extensively but with varied success. More randomized clinical trials are needed to address this issue. However, if immediate manual placenta removal service is unavailable, a trial of intra-umbilical vein oxytocin 100 IU at a total volume of at least 40 mL while preparing for transfer to a tertiary center or theatre may result in spontaneous expulsion of the placenta.
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Rodgers BC, Pasternak A, Gray R. A novel treatment for management of a trapped placenta using intracervical nitroglycerin tablets. BMJ Case Rep 2013; 2013:bcr-2013-010505. [PMID: 24014558 DOI: 10.1136/bcr-2013-010505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 34-year-old gravida 2, para 1 woman delivered a viable male infant and developed retained placenta due to entrapment. A nitroglycerin tablet was used to relax the lower uterine segment and cervix, which allowed the placenta to pass through the cervix for delivery. The nitroglycerin tablet was placed in the cervix and held in place by the delivering physician as it dissolved. Soon after administration, the intact placenta delivered. The patient did not experience the typical side effects of headache, asymptomatic decrease in blood pressure, hypotension, palpitations or dizziness that can be associated with administration of nitroglycerin. We suspect that this novel localised route of nitroglycerin administration may be an effective management strategy to treat trapped placenta while minimising side effects. However, the outcomes of this treatment would require further study.
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Affiliation(s)
- Blake Conley Rodgers
- Department of Family Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
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Nankali A, Keshavarzi F, Fakheri T, Zare S, Rezaei M, Daeichin S. Effect of intraumbilical vein oxytocin injection on third stage of labor. Taiwan J Obstet Gynecol 2013; 52:57-60. [DOI: 10.1016/j.tjog.2013.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2012] [Indexed: 11/25/2022] Open
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van Stralen G, Veenhof M, Holleboom C, van Roosmalen J. No reduction of manual removal after misoprostol for retained placenta: a double-blind, randomized trial. Acta Obstet Gynecol Scand 2013; 92:398-403. [PMID: 23231499 DOI: 10.1111/aogs.12065] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2012] [Accepted: 12/06/2012] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To test the effect of 800 μg of misoprostol orally on the prevention of manual removal of retained placenta. DESIGN Multicenter, double-blinded, placebo-controlled, randomized trial. SETTING One university and one non-university teaching hospital in the Netherlands. SAMPLE 99 women with retained placenta (longer than 60 min after childbirth) in the absence of postpartum hemorrhage. METHODS Eligible women were administered either 800 μg of misoprostol or placebo orally. MAIN OUTCOME MEASURES Number of manual removals of retained placenta and amount of blood loss. RESULTS Manual removal of retained placenta was performed in 50% of the women who received misoprostol and in 55% who received placebo (relative risk 0.91, 95% confidence interval 0.62-1.34). No difference in the amount of blood loss (970 vs. 1120 mL; p = 0.34) was observed between the two groups. CONCLUSIONS Administration of 800 μg of oral misoprostol, one hour after childbirth, does not seem to reduce the number of manual removals of retained placentas. The time elapsing results in the delivery of 50% of the retained placentas at the expense of an increased risk of postpartum hemorrhage.
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Affiliation(s)
- Giel van Stralen
- Department of Obstetrics, Leiden University Medical Centre, Leiden, The Netherlands.
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Nitroglycerin for management of retained placenta: a multicenter study. Obstet Gynecol Int 2012; 2012:321207. [PMID: 22685465 PMCID: PMC3364587 DOI: 10.1155/2012/321207] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2012] [Revised: 03/21/2012] [Accepted: 03/22/2012] [Indexed: 11/17/2022] Open
Abstract
The primary aim was to determine if sequential administration of oxytocin and nitroglycerin is effective for management of retained placenta when performed by obstetricians with no experience of the method. Secondary aims were to examine possible adverse effects of nitroglycerin. One hundred and five women with retained placenta were randomly selected to receive either 1 mg nitroglycerin or placebo tablets sublingually if intravenous oxytocin had failed to expel the placenta. At two of the hospitals some of the midwives were familiar with the use of nitroglycerin. The other midwives and all the participating obstetricians had no clinical experience of the method. In the treatment group, detachment of placenta following nitroglycerin occurred in 37.3% of the women compared to 20.4% in the placebo group (P = 0.056). In the two hospitals with some experience of the method, placenta was removed in 9 of 19 (47.4%) women in the nitroglycerin group compared to 3 of 17 (15.0%) women in the placebo group. No adverse effects of clinical importance were registered. Although the difference between the two groups did not reach statistical significance, the higher success rate in the two hospitals with some experience could indicate that clinical experience is of importance in order to achieve placental detachment.
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Abstract
BACKGROUND Retained placenta affects 0.5% to 3% of women following delivery, with considerable morbidity if left untreated. Use of tocolytics, either alone or in combination with uterotonics, may be of value to minimise the need for manual removal of the placenta in theatre under anaesthesia. OBJECTIVES Evaluate the benefits and harms of tocolytics alone or in addition to uterotonics in the management of retained placenta in order to reduce the need for manual removal of placenta. SEARCH STRATEGY We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2010) and contacted experts in the field. SELECTION CRITERIA Any adequately randomised controlled trial (RCT) comparing the use of tocolytics, either alone or in combination with uterotonics, with no intervention or with other interventions in the management of retained placenta. All women having a vaginal delivery with a retained placenta, regardless of the management of the third stage of labour (expectant or active). We included all trials with haemodynamically stable women in whom the placenta was not delivered at least within 15 minutes after delivery of the baby. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. Consultation of the third author was done if needed. MAIN RESULTS We included one RCT (involving 24 women). It compared the use of nitroglycerin tablets versus placebo after the treatment with oxytocin failed. There was a statistically significant reduction in the need for manual removal of placenta (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.66). There was also a statistically significant reduction in mean blood loss during the third stage of labour (mean difference (MD) -262.50 ml, 95% CI -364.95 to -160.05). Sublingual nitroglycerin caused some haemodynamic changes as it lowers the systolic blood pressure and diastolic blood pressure by a means of 6 and 5 mmHg respectively. Pulse rate increased by a mean of two beats per minute. AUTHORS' CONCLUSIONS Sublingual nitroglycerin, given when oxytocin fails, seems to reduce both the need for manual removal of placenta and blood loss during the third stage of labour when compared to placebo. Further trials are needed to confirm its clinical role and safety. Its routine use cannot be recommended based on a single small study. There is no evidence available for other types of tocolytics.
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Affiliation(s)
- Hany Abdel-Aleem
- Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University Hospital, Assiut, Egypt, 71511
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Visalyaputra S, Prechapanich J, Suwanvichai S, Yimyam S, Permpolprasert L, Suksopee P. Intravenous nitroglycerin for controlled cord traction in the management of retained placenta. Int J Gynaecol Obstet 2010; 112:103-6. [PMID: 21144515 DOI: 10.1016/j.ijgo.2010.08.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2010] [Revised: 08/16/2010] [Accepted: 10/29/2010] [Indexed: 01/26/2023]
Abstract
OBJECTIVE To determine the effect of 200 μg of intravenous nitroglycerin in the release of retained placenta by controlled cord traction. METHODS In this randomized controlled study, 40 women with a placenta retained for 30 minutes received intravenously 200 μg of nitroglycerin or a normal saline solution before umbilical cord traction was initiated. The rates of successful removal of the retained placenta in the study (n=20) and control (n=20) groups were compared, as were blood pressure, pulse rate, blood loss, and adverse effects. RESULTS The placenta was released in only 15% and 20% of the participants in the study and control group, respectively. The remainder of the participants required general anesthesia and manual removal of the retained placenta regardless of group assignation. Blood pressure fell in significantly more women in the study group, but there were no differences in estimated blood loss or minor adverse effects. CONCLUSION Intravenously administered nitroglycerin did not facilitate the release of retained placenta by umbilical cord traction. However, cord traction may be performed longer than 30 minutes to attempt releasing the placenta before operative manual removal is initiated.
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Abstract
Management of post-partum haemorrhage (PPH) involves the treatment of uterine atony, evacuation of retained placenta or placental fragments, surgery due to uterine or birth canal trauma, balloon tamponade, effective volume replacement and transfusion therapy, and occasionally, selective arterial embolization. This article aims at introducing pregnancy- and haemorrhage-induced changes in coagulation and fibrinolysis and their relevant compensatory mechanisms, volume replacement therapy, optimal transfusion of blood products, and coagulation factor concentrates, and briefly cell salvage, management of uterine atony, surgical interventions, and selective arterial embolization. Special attention, respective management, and follow-up are required in women with bleeding disorders, such as von Willebrand disease, carriers of haemophilia A or B, and rare coagulation factor deficiencies. We also provide a proposal for practical instructions in the treatment of PPH.
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Affiliation(s)
- J Ahonen
- Departments of Anaesthesia and Intensive Care, Helsinki University Hospital, Finland.
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Abstract
The incidence and importance of retained placenta (RP) varies greatly around the world. In less developed countries, it affects about 0.1% of deliveries but has up to 10% case fatality rate. In more developed countries, it is more common (about 3% of vaginal deliveries) but very rarely associated with mortality. There are three main types of retained placenta following the vagina delivery: placenta adherens (when there is failed contraction of the myometrium behind the placenta), trapped placenta (a detached placenta trapped behind a closed cervix) and partial accreta (when there is a small area of accreta preventing detachment). All can be treated by manual removal of placenta, which should be carried out at 30-60 minutes postpartum. Medical management is also an option for placenta adherens and trapped placenta. The need for manual removal can be reduced by 20% by the use of intraumbilical oxytocin (30 i.u. in 30 mL saline). A trapped placenta may respond to glyceryl trinitrate (500 mcg sublingually) or gentle, persistent, controlled cord traction.
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Affiliation(s)
- Andrew D Weeks
- School of Reproductive and Developmental Medicine, Liverpool Women's Hospital, Crown Street, Liverpool L8 7SS, UK.
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Roth A, Elkayam U. Acute myocardial infarction associated with pregnancy. J Am Coll Cardiol 2008; 52:171-80. [PMID: 18617065 DOI: 10.1016/j.jacc.2008.03.049] [Citation(s) in RCA: 225] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2008] [Revised: 03/11/2008] [Accepted: 03/18/2008] [Indexed: 01/30/2023]
Abstract
Acute myocardial infarction (AMI) during pregnancy or the early post-partum period is rare but has been shown to be associated with poor maternal as well as fetal outcome. Major changes in both diagnosis and treatment of AMI in the nonpregnant patient have lead to improved outcome which may also affect pregnant patients. The purpose of this paper is to review available information related to the pathophysiology and clinical profile and provide recommendations for the diagnosis and management of AMI occuring during pregnancy and the early post-partum period.
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Affiliation(s)
- Arie Roth
- Department of Cardiology Tel Aviv Sourasky Medical Center, Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel
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