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1.
Am J Obstet Gynecol ; 219(1): 101.e1-101.e12, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29660299

RESUMO

BACKGROUND: Preterm premature rupture of membranes is a leading contributor to maternal and neonatal morbidity and death. Epidemiologic and experimental studies have demonstrated that thrombin causes fetal membrane weakening and subsequently preterm premature rupture of membranes. Although blood is suspected to be the likely source of thrombin in fetal membranes and amniotic fluid of patients with preterm premature rupture of membranes, this has not been proved. Ureaplasma parvum is emerging as a pathogen involved in prematurity, which includes preterm premature rupture of membranes; however, until now, prothrombin production that has been induced directly by bacteria in fetal membranes has not been described. OBJECTIVE: This study was designed to investigate whether Ureaplasma parvum exposure can induce prothrombin production in fetal membranes cells. STUDY DESIGN: Primary fetal membrane cells (amnion epithelial, chorion trophoblast, and decidua stromal) or full-thickness fetal membrane tissue explants from elective, term, uncomplicated cesarean deliveries were harvested. Cells or tissue explants were infected with live Ureaplasma parvum (1×105, 1×106 or 1×107 colony-forming units per milliliter) or lipopolysaccharide (Escherichia coli J5, L-5014; Sigma Chemical Company, St. Louis, MO; 100 ng/mL or 1000 ng/mL) for 24 hours. Tissue explants were fixed for immunohistochemistry staining of thrombin/prothrombin. Fetal membrane cells were fixed for confocal immunofluorescent staining of the biomarkers of fetal membrane cell types and thrombin/prothrombin. Protein and messenger RNA were harvested from the cells and tissue explants for Western blot or quantitative reverse transcription polymerase chain reaction to quantify thrombin/prothrombin protein or messenger RNA production, respectively. Data are presented as mean values ± standard errors of mean. Data were analyzed using 1-way analysis of variance with post hoc Dunnett's test. RESULTS: Prothrombin production and localization were confirmed by Western blot and immunostainings in all primary fetal membrane cells and tissue explants. Immunofluorescence observations revealed a perinuclear localization of prothrombin in amnion epithelial cells. Localization of prothrombin in chorion and decidua cells was perinuclear and cytoplasmic. Prothrombin messenger RNA and protein expression in fetal membranes were increased significantly by Ureaplasma parvum, but not lipopolysaccharide, treatments in a dose-dependent manner. Specifically, Ureaplasma parvum at a dose of 1×107 colony-forming units/mL significantly increased both prothrombin messenger RNA (fold changes in amnion: 4.1±1.9; chorion: 5.7±4.2; decidua: 10.0±5.4; fetal membrane: 9.2±3.0) and protein expression (fold changes in amnion: 138.0±44.0; chorion: 139.6±15.1; decidua: 56.9±29.1; fetal membrane: 133.1±40.0) compared with untreated control subjects. Ureaplasma parvum at a dose of 1×106 colony-forming units/mL significantly up-regulated prothrombin protein expression in chorion cells (fold change: 54.9±5.3) and prothrombin messenger RNA expression in decidua cells (fold change: 4.4±1.9). CONCLUSION: Our results demonstrate that prothrombin can be produced directly by fetal membrane amnion, chorion, and decidua cells. Further, prothrombin production can be stimulated by Ureaplasma parvum exposure in fetal membranes. These findings represent a potential novel underlying mechanism of Ureaplasma parvum-induced rupture of fetal membranes.


Assuntos
Células Epiteliais/metabolismo , Membranas Extraembrionárias/metabolismo , Ruptura Prematura de Membranas Fetais/genética , Protrombina/genética , Células Estromais/metabolismo , Trombina/genética , Trofoblastos/metabolismo , Infecções por Ureaplasma/genética , Âmnio/citologia , Western Blotting , Córion/citologia , Decídua/citologia , Membranas Extraembrionárias/citologia , Feminino , Ruptura Prematura de Membranas Fetais/metabolismo , Ruptura Prematura de Membranas Fetais/microbiologia , Humanos , Técnicas In Vitro , Lipopolissacarídeos , Gravidez , Protrombina/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trombina/metabolismo , Ureaplasma , Infecções por Ureaplasma/metabolismo , Infecções por Ureaplasma/microbiologia
2.
Can J Anaesth ; 65(3): 254-262, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29209926

RESUMO

PURPOSE: Hypotension is common after spinal anesthesia for Cesarean delivery. It is associated with nausea, vomiting, and fetal acidosis. Previous research on phenylephrine excluded obese subjects. We compared the incidence of intraoperative nausea and vomiting (IONV) in obese patients who received a prophylactic phenylephrine infusion vs those who received bolus dosing for the treatment of spinal-induced hypotension. METHODS: In this multicentre, double-blinded randomized controlled trial, 160 obese women undergoing elective Cesarean delivery under spinal anesthesia were randomized to receive a prophylactic phenylephrine infusion initiated at 50 µg·min-1 (and titrated according to a predefined algorithm) or 100 µg phenylephrine boluses to treat hypotension. Maternal systolic blood pressure was maintained within 20% of baseline. The primary study outcome was the incidence of IONV. RESULTS: Intraoperative nausea and vomiting were significantly reduced in the infusion group compared to the bolus group (46% vs 75%, respectively; relative risk [RR], 0.61; 95% confidence interval [CI], 0.47 to 0.80; P < 0.001). This was associated with significantly reduced need for intraoperative rescue antiemetics (26% vs 42%, respectively; RR, 0.62; 95% CI, 0.40 to 0.97; P = 0.04), but no difference in the incidence of vomiting. Postoperative vomiting at two hours was reduced in the infusion group (11% vs 25%; RR, 0.44; 95% CI, 0.21 to 0.90; P = 0.02);however, there were no differences in the incidence or severity of postoperative nausea, need for rescue antiemetics at two hours and 24 hr, or the incidence of postoperative vomiting at 24 hr. CONCLUSION: In obese women undergoing Cesarean delivery with spinal anesthesia, prophylactic phenylephrine infusion was associated with less intraoperative nausea, less need for rescue antiemetics, and reduced early postoperative vomiting. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01481740). Registered 22 July 2011.


Assuntos
Cesárea/métodos , Hipotensão/prevenção & controle , Fenilefrina/administração & dosagem , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adulto , Anestesia Obstétrica/métodos , Raquianestesia/métodos , Antieméticos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Incidência , Infusões Intravenosas , Injeções Intravenosas , Obesidade/complicações , Náusea e Vômito Pós-Operatórios/epidemiologia , Gravidez , Vasoconstritores/administração & dosagem
3.
Am J Perinatol ; 35(1): 78-83, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28806846

RESUMO

OBJECTIVE: Total dose of oxytocin received during labor is an important variable in studies of human labor but is difficult to calculate. We sought to identify a surrogate measure for total dose of oxytocin received. STUDY DESIGN: For each subject receiving oxytocin during labor, the oxytocin total dose received in labor was calculated as the area under the curve. Maximal oxytocin infusion rate, total duration of oxytocin infusion, and the product of both, defined as the oxytocin product, were then each correlated with the total dose of oxytocin received using the Pearson's correlation coefficient. RESULTS: Oxytocin dosing data were available from 402 women at Duke and 6,907 women from Pithagore6. The two variables alone, or combined as the oxytocin product, demonstrated a high correlation with the oxytocin total dose (r > 0.7), with the oxytocin product demonstrating the highest (r > 0.9). This was true whether labor was induced or augmented and whether delivery was vaginal or cesarean. CONCLUSION: The oxytocin product, composed of two easily obtained variables, demonstrated a very high correlation with total oxytocin dose received in labor and represents a simple and accurate surrogate for total dose of oxytocin received during labor. The oxytocin product can be used in clinical studies in which oxytocin dose is an important variable.


Assuntos
Trabalho de Parto Induzido/métodos , Trabalho de Parto/efeitos dos fármacos , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Adulto , Cesárea/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Adulto Jovem
4.
Anesth Analg ; 120(5): 1085-1094, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25806402

RESUMO

BACKGROUND: Current treatment modalities for preventing preterm premature rupture of membranes are limited, but progestins may play a role. Tumor necrosis factor α (TNFα) enhances matrix metalloproteinase-9 (MMP-9) gene expression and activity in fetal membranes, contributing to membrane weakening and rupture. We previously demonstrated that progestins attenuate TNFα-induced MMP-9 activity in a cytotrophoblast cell line. However, whether they have a similar effect in primary amnion and chorion cells of fetal membranes is unknown. In this study, we evaluated the effect of progestins on basal and TNFα-induced MMP-9 activity and gene expression in primary chorion and amnion cells harvested from the fetal membranes of term nonlaboring patients. METHODS: Primary amnion and chorion cells were isolated from fetal membranes obtained from term uncomplicated nonlaboring patients following elective cesarean delivery (n = 11). Confluent primary amnion and chorion cell cultures were both pretreated with vehicle (control), progesterone (P4), 17α-hydroxyprogesterone caproate (17P), or medroxyprogesterone acetate (MPA) at 10 M concentration for 6 hours followed by stimulation with TNFα at 10 ng/mL for an additional 24 hours. Cell cultures pretreated with the vehicle only served as the unstimulated control and the vehicle stimulated with TNFα served as the stimulated control. Both controls were assigned a value of 100 units. Cell culture medium was harvested for MMP-9 enzymatic activity quantification using gelatin zymography. Total RNA was extracted for quantifying MMP-9 gene expression using real-time quantitative PCR. Basal MMP-9 activity and gene expression data were normalized to the unstimulated control. TNFα-stimulated MMP-9 activity and gene expression were normalized to the stimulated control. The primary outcome was the effect of progestins on TNFα-induced MMP-9 enzymatic activity in term human primary amnion and chorion cells in vitro. Secondary outcomes included the effect of progestin therapy on TNFα-induced MMP-9 gene expression and on basal MMP-9 activity and gene expression in primary amnion and chorion cells in vitro. RESULTS: Primary cells were harvested from 11 patients. Compared with the unstimulated control, TNFα increased MMP-9 activity (P = 0.005 versus control in primary amnion cells and P < 0.001 versus control in primary chorion cells) and MMP-9 gene expression (P = 0.030 versus control in primary amnion cells, P < 0.001 versus control in primary chorion cells). Compared with the unstimulated controls, MPA, but not P4 or 17P, reduced basal MMP-9 activity [mean difference (95% CI) -49.6 (-81.9, -17.3) units, P = 0.001] and gene expression [mean difference (95% CI) -53.4 (-105.9, -0.9) units, P = 0.045] in primary amnion cells. Compared with the stimulated control, MPA also reduced TNFα-induced MMP-9 activity [mean difference (95% CI) -69.0 (-91.8, -46.3) units, P < 0.001] and gene expression [mean difference (95% CI) -86.0 (-120.7, -51.3) units, P < 0.001] in primary amnion cells. Progestin pretreatment had no significant effect on basal or TNFα-induced MMP-9 activity and gene expression in primary chorion cells. CONCLUSIONS: The inhibitory effect of MPA on both basal and TNFα-induced MMP-9 activity and gene expression in primary amnion cells demonstrate a possible mechanism by which progestins may prevent fetal membrane weakening leading to preterm premature rupture of membranes.


Assuntos
Âmnio/efeitos dos fármacos , Córion/efeitos dos fármacos , Hidroxiprogesteronas/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Acetato de Medroxiprogesterona/farmacologia , Progesterona/farmacologia , Progestinas/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Caproato de 17 alfa-Hidroxiprogesterona , Âmnio/citologia , Âmnio/enzimologia , Células Cultivadas , Córion/citologia , Córion/enzimologia , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 9 da Matriz/genética , Gravidez , RNA Mensageiro/biossíntese
5.
Can J Anaesth ; 62(3): 278-88, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25501493

RESUMO

PURPOSE: This study examines the peripartum anesthetic management and outcomes of women with dilated cardiomyopathy in a large university medical centre over a seven-year period. PRINCIPAL FINDINGS: Twenty-five women were included in this series, 18 with a new diagnosis of cardiomyopathy and seven with a history of cardiomyopathy. Sixteen patients (64%) identified themselves as African American, seven (28%) were Caucasian, and two patients (8%) were Hispanic. The median (range) gestational age at the time of a new diagnosis of cardiomyopathy was 29 (7-38) weeks. Eight women (32%) had New York Heart Association class III/IV symptoms at the time of delivery or in the immediate postpartum period. A multidisciplinary team of obstetricians, anesthesiologists, cardiologists, and pediatricians were involved in the care of these women. The median (range) gestational age at the time of delivery was 33.5 (30-40) weeks. There were nine vaginal deliveries and 15 operative deliveries. One patient had fetal loss at 19 weeks gestation. Twelve women had labour induced with an intravenous infusion of oxytocin at a rate of 0.001-0.02 IU·min(-1). An oxytocin infusion at a variable rate with a maximum dose of 0.05 IU·min(-1) was administered after vaginal delivery to maintain uterine tone. Epidural analgesia was initiated prior to induction of labour or in the latent phase of labour. Seven Cesarean deliveries were performed under combined spinal-epidural anesthesia, five were performed under epidural anesthesia, and three women had general anesthesia. Oxytocin was administered via an intravenous infusion at a rate of 0.05-0.2 IU·min(-1) after operative delivery. One patient had a cardiac arrest on induction of general anesthesia and was successfully resuscitated. There were no maternal or neonatal deaths. Ten women were followed up at our institution and at six months postpartum; 50% of these patients were still symptomatic. CONCLUSION: We report favourable outcomes in 25 pregnant women with dilated cardiomyopathy who were managed by a multidisciplinary team.


Assuntos
Centros Médicos Acadêmicos , Anestesia Obstétrica/métodos , Cardiomiopatia Dilatada/complicações , Parto Obstétrico/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Complicações Cardiovasculares na Gravidez , Adulto , Anestesia Epidural , Anestesia Geral , Raquianestesia , Parto Obstétrico/estatística & dados numéricos , Feminino , Morte Fetal , Parada Cardíaca , Humanos , Trabalho de Parto , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Gravidez
6.
Blood Adv ; 8(2): 287-295, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38039512

RESUMO

ABSTRACT: The hemostatic system is upregulated to protect pregnant mothers from hemorrhage during childbirth. Studies of the details just before and after delivery, however, are lacking. Recombinant factor VIIa (rFVIIa) has recently been granted approval by the European Medicines Agency for the treatment of postpartum hemorrhage (PPH). A next-generation molecule, CT-001, is being developed as a potentially safer and more efficacious rFVIIa-based therapy. We sought to evaluate the peripartum hemostatic status of pregnant women and assess the ex vivo hemostatic activity of rFVIIa and CT-001 in peripartum blood samples. Pregnant women from 2 study sites were enrolled in this prospective observational study. Baseline blood samples were collected up to 3 days before delivery. Postdelivery samples were collected 45 (±15) minutes after delivery. Between the 2 time points, soluble fibrin monomer and D-dimer increased whereas tissue factor, FVIII, FV, and fibrinogen decreased. Interestingly, the postdelivery lag time and time to peak in the thrombin generation assay were shortened, and the peak thrombin generation capacity was maintained despite the reduced levels of coagulation proteins after delivery. Furthermore, both rFVIIa and CT-001 were effective in enhancing clotting activity of postdelivery samples in activated partial thromboplastin time, prothrombin time, thrombin generation, and viscoelastic hemostatic assays, with CT-001 demonstrating greater activity. In conclusion, despite apparent ongoing consumption of coagulation factors at the time of delivery, thrombin output was maintained. Both rFVIIa and CT-001 enhanced the upregulated hemostatic activity in postdelivery samples, and consistent with previous studies comparing CT-001 and rFVIIa in vitro and in in vivo, CT-001 demonstrated greater activity than rFVIIa.


Assuntos
Hemostáticos , Hemorragia Pós-Parto , Feminino , Humanos , Gravidez , Fatores de Coagulação Sanguínea , Fator VIIa/farmacologia , Hemostáticos/farmacologia , Período Pós-Parto , Trombina , Tomografia Computadorizada por Raios X
8.
Anesth Analg ; 116(1): 133-44, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23223119

RESUMO

BACKGROUND: The current standard labor epidural analgesic regimens consist of a local anesthetic in combination with an opioid delivered via continuous epidural infusion (CEI). With CEI local anesthetic, doses may be large with resulting profound motor blockade potentially affecting the incidence of instrumental deliveries. In this systematic review of randomized controlled trials (RCTs), we compared the effect of intermittent epidural bolus (IEB) to standard CEI dosing with or without patient-controlled epidural analgesia on patient satisfaction, the need for manual anesthesia interventions, labor progression, and mode of delivery in healthy women receiving labor epidural analgesia. METHODS: A systematic review of RCTs that compared CEI with IEB for labor analgesia was performed. The articles were evaluated for validity, and data were extracted by the authors and summarized using odds ratios (ORs), mean differences (MDs), and 95% confidence intervals (CIs). RESULTS: Nine RCTs were included in this systematic review. Three hundred forty-four subjects received CEI, whereas 350 subjects received IEB labor analgesia. All 9 studies were deemed to be low risk of bias. There was no statistical difference detected between IEB and CEI in the rate of cesarean delivery (OR, 0.87; 95% CI, 0.56-1.35), duration of labor (MD, -17 minutes; 95% CI, -42 to 7), or the need for anesthetic intervention (OR, 0.56; 95% CI, 0.29-1.06). IEB did result in a small but statistically significant reduction in local anesthetic usage (MD, -1.2 mg bupivacaine equivalent per hour; 95% CI, -2.2 to -0.3). Maternal satisfaction score (100-mm visual analog scale) was higher with IEB (MD, 7.0 mm; 95% CI, 6.2-7.8). CONCLUSIONS: IEB is an appealing concept; current evidence suggests IEB slightly reduces local anesthetic usage and improves maternal satisfaction. Given the wide CIs of the pooled results for many outcomes, definite conclusions cannot be drawn for those outcomes, but there is also a potential that IEB improves instrumental delivery rate and need of anesthesia interventions. More study is required to conceptualize the ideal IEB regimen and investigate its effect on labor analgesia and obstetric outcomes.


Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Adulto , Analgesia Controlada pelo Paciente , Anestesia Obstétrica , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Injeções Epidurais , Satisfação do Paciente , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Anesth Analg ; 117(6): 1368-70, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24257387

RESUMO

Respiratory depression can occur after neuraxial morphine administration. In the obstetric population, there are little data on respiratory depression after neuraxial morphine administration in women undergoing cesarean delivery. In this single-center, retrospective study in 5036 obstetric patients (mean body mass index = 34 kg/m) who underwent cesarean delivery and received neuraxial morphine, we did not identify any instances of respiratory depression requiring naloxone administration or rapid response team involvement. Therefore, the upper 95% confidence limit for respiratory depression in our study is 0.07% (1 event per 1429 cases).


Assuntos
Analgésicos Opioides/efeitos adversos , Cesárea/efeitos adversos , Morfina/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Insuficiência Respiratória/induzido quimicamente , Centros Médicos Acadêmicos , Adulto , Analgésicos Opioides/administração & dosagem , Feminino , Humanos , Incidência , Morfina/administração & dosagem , North Carolina/epidemiologia , Obesidade/epidemiologia , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Insuficiência Respiratória/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Environ Epigenet ; 9(1): dvac026, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36694712

RESUMO

Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother-child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother-child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76-1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.

11.
Clin Appl Thromb Hemost ; 29: 10760296231175089, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37186763

RESUMO

AIM: This study aims to investigate the ability of fibrinogen and rotational thromboelastometry (ROTEM) parameters measured at obstetric hemorrhage protocol initiation to predict severe hemorrhage. METHODS: In this retrospective study we included patients whose hemorrhage was managed with an obstetric massive transfusion protocol. Fibrinogen and ROTEM parameters EXTEM clotting time (CT), clot formation time (CFT), alpha angle, A10, A20, lysis index 30 min after CT (LI30), FIBTEM A10, A20, were measured at initiation of the protocol with transfusion based on a predefined algorithm. Patients were grouped into either severe or nonsevere hemorrhage based on: peripartum fall in hemoglobin ≥4 g/dL, transfusion of ≥4 units of blood product, invasive procedures for hemorrhage control, intensive care unit admission, or death. RESULTS: Of the 155 patients included, 108 (70%) progressed to severe hemorrhage. Fibrinogen, EXTEM alpha angle, A10, A20, FIBTEM A10, A20 were significantly lower in the severe hemorrhage group while the CFT was significantly prolonged in the severe hemorrhage group. In univariate analysis, predicted progression to severe hemorrhage yielded areas under the receiver operating characteristic curve (95% confidence interval [CI]) of: fibrinogen: 0.683 (0.591-0.776), CFT: 0.671 (0.553, 0.789), EXTEM alpha angle: 0.690 (0.577-0.803), A10: 0.693 (0.570-0.815), A20: 0.678 (0.563-0.793), FIBTEM A10: 0.726 (0.605-0.847), and A20: 0.709 (0.594-0.824). In a multivariable model, fibrinogen was independently associated with severe hemorrhage (odds ratio [95% CI] = 1.037 [1.009-1.066]) for every 50 mg/dL decrease in fibrinogen drawn at obstetric hemorrhage massive transfusion protocol initiation. CONCLUSION: Both fibrinogen and ROTEM parameters measured at the initiation of an obstetric hemorrhage protocol are useful parameters for predicting severe hemorrhage.


Assuntos
Fibrinogênio , Hemostáticos , Feminino , Gravidez , Humanos , Tromboelastografia/métodos , Estudos Retrospectivos , Hemorragia/etiologia
12.
Anesth Analg ; 114(4): 813-22, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22344239

RESUMO

BACKGROUND: We performed a systematic review to assess the efficacy of dexamethasone in reducing postoperative nausea, vomiting (PONV), pruritus, and enhancing postoperative analgesia in patients receiving neuraxial anesthesia with neuraxial morphine. METHODS: We searched Medline (1966-2011), the Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science for all randomized controlled trials comparing dexamethasone with placebo for the prevention of PONV and/or pruritus in patients receiving neuraxial morphine as part of a neuraxial anesthetic technique. Data were extracted independently by the authors on the incidence of PONV, pruritus, pain scores at 4 and 24 hours, and use of rescue antiemetics, antipruritics, and analgesics. RESULTS: Eight randomized controlled trials (4 cesarean deliveries, 4 total abdominal hysterectomies) were included. From these trials, 768 patients were analyzed with 473 receiving dexamethasone and 295 receiving placebo. The doses of dexamethasone investigated ranged from 2.5 to 10 mg. Dexamethasone reduced the incidence of postoperative nausea (relative risk, RR [95% confidence interval, CI] = 0.57 [0.45, 0.72]), vomiting (RR [95% CI] = 0.56 [0.43, 0.72]), and the use of rescue antiemetic therapy (RR [95% CI] = 0.47 [0.36, 0.61]) compared with placebo. There was no evidence of dose responsiveness with respect to its antiemetic effect. Dexamethasone also reduced 24-hour visual analog pain scores (measured on an 11-point scale [0-10]) (mean difference [95% CI] = -0.30 [-0.46, -0.13]) and the use of rescue analgesics (RR [95% CI] = 0.72 [0.52, 0.98]). Dexamethasone did not reduce the incidence of pruritus (RR [95% CI] = 0.98 [0.84, 1.15]). Examination of the funnel plots and Egger's test revealed evidence of publication bias in the primary outcomes. CONCLUSION: Dexamethasone is an effective antiemetic for patients receiving neuraxial morphine for cesarean delivery and abdominal hysterectomy. In addition, the doses used for antiemetic prophylaxis enhanced postoperative analgesia compared with placebo. However, dexamethasone was not effective for the prophylaxis against neuraxial morphine-induced pruritus.


Assuntos
Analgésicos Opioides/efeitos adversos , Antieméticos/uso terapêutico , Dexametasona/uso terapêutico , Morfina/efeitos adversos , Náusea e Vômito Pós-Operatórios/prevenção & controle , Antieméticos/efeitos adversos , Cesárea , Dexametasona/efeitos adversos , Feminino , Humanos , Histerectomia , Injeções Espinhais , Morfina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Prurido/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Am J Obstet Gynecol ; 204(1): 65.e1-6, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20869036

RESUMO

OBJECTIVE: We sought to assess perioperative outcomes of minimally invasive vs open endometrial cancer staging procedures. STUDY DESIGN: A total of 181 consecutive patients underwent open or minimally invasive hysterectomy with or without lymphadenectomy. Perioperative outcomes, analgesic, and antiemetic use were compared. RESULTS: In all, 97 and 84 women underwent open and minimally invasive staging procedures, respectively. In the open staging group, median anesthesia time was shorter (197 vs 288 minutes; P < .0001), but recovery room stay (168 vs 140 minutes; P = .01) and hospital stay (4 vs 1 day; P < .0001) were longer. Median narcotic (13 vs 43 mg morphine equivalents; P < .0001) and antiemetic (43% vs 25%; P = .01) use were lower for minimally invasive surgery in the first 24 hours postoperatively. Median estimated blood loss was lower for minimally invasive procedures (100 vs 300 mL; P < .0001). CONCLUSION: Minimally invasive staging for endometrial cancer is associated with lower use of narcotics and antiemetics, and shorter hospital stay compared to open procedures.


Assuntos
Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Antieméticos/administração & dosagem , Neoplasias do Endométrio/patologia , Histerectomia/métodos , Estadiamento de Neoplasias/métodos , Perda Sanguínea Cirúrgica , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/efeitos adversos , Tempo de Internação , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Estudos Retrospectivos , Robótica/métodos , Fatores de Tempo
14.
Anesthesiol Res Pract ; 2021: 4750149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603442

RESUMO

OBJECTIVES: Dexamethasone has been shown to have analgesic properties in the general surgical population. However, the analgesic effects for women that undergo cesarean deliveries under spinal anesthesia remain unclear and may be related to the timing of dexamethasone administration. We hypothesized that intravenous dexamethasone administered before skin incision would significantly reduce postoperative opioid consumption at 24 h after cesarean delivery under spinal anesthesia with intrathecal morphine. METHODS: Women undergoing elective cesarean deliveries under spinal anesthesia were randomly assigned to receive 8 mg of intravenous dexamethasone or placebo prior to skin incision. Both groups received a standardized spinal anesthetic and multimodal postoperative analgesic regime. The primary outcome was cumulative opioid consumption at 24 h. Secondary outcomes included cumulative opioid consumption at 48 h, time to first analgesic request, and pain scores at rest and on movement at 2, 24, and 48 h. RESULTS: 47 patients were analyzed-23 subjects that received dexamethasone and 24 subjects that received placebo. There was no difference in the median (Q1, Q3) cumulative opioid consumption in the first 24 hours following cesarean delivery between the dexamethasone group {15 (7.5, 20.0) mg} and the placebo group {13.75 (2.5, 31.25) mg} (P=0.740). There were no differences between the groups in cumulative opioid consumption at 48 h, time to first analgesic request, and pain scores. CONCLUSIONS: Intravenous dexamethasone 8 mg administered prior to skin incision did not reduce the opioid consumption of women that underwent cesarean deliveries under spinal anesthesia with intrathecal morphine and multimodal postoperative analgesic regimen.

15.
Pediatr Obes ; 16(7): e12763, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33381912

RESUMO

BACKGROUND: Although maternal systemic inflammation is hypothesized to link maternal pre-pregnancy obesity to offspring metabolic dysfunction, patient empirical data are limited. OBJECTIVES: In this study, we hypothesized that pre-pregnancy obesity alters systemic chemo/cytokines concentrations in pregnancy, and this alteration contributes to obesity in children. METHODS: In a multi-ethnic cohort of 361 mother-child pairs, we measured prenatal concentrations of plasma TNF-α, IL-6, IL-8, IL-1ß, IL-4, IFN-γ, IL-12 p70 subunit, and IL-17A using a multiplex ELISA and examined associations of pre-pregnancy obesity on maternal chemo/cytokine levels, and associations of these cytokine levels with offspring body mass index z score (BMI-z) at age 2-6 years using linear regression. RESULTS: After adjusting for maternal smoking, ethnicity, age, and education, pre-pregnancy obesity was associated with increased concentrations of TNF-α (P = .026) and IFN-γ (P = .06). While we found no evidence for associations between TNF-α concentrations and offspring BMI-z, increased IFN-γ concentrations were associated with decreased BMI-z (P = .0002), primarily in Whites (P = .0011). In addition, increased maternal IL-17A concentrations were associated with increased BMI-z in offspring (P = .0005) with stronger associations in African Americans (P = .0042) than Whites (P = .24). CONCLUSIONS: Data from this study are consistent with maternal obesity-related inflammation during pregnancy, increasing the risk of childhood obesity in an ethnic-specific manner.


Assuntos
Citocinas/sangue , Obesidade Materna , Obesidade Infantil , Negro ou Afro-Americano , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Obesidade Materna/epidemiologia , Obesidade Infantil/epidemiologia , Gravidez , População Branca
16.
Anesth Analg ; 111(5): 1221-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20495139

RESUMO

BACKGROUND: The administration of prophylactic phenylephrine infusions in combination with fluid cohydration significantly reduces the incidence of hypotension in women having cesarean delivery under spinal anesthesia. The ideal dosing regimen for this purpose is not known. In this study, we investigated the dose of phenylephrine that, when administered as a prophylactic fixed rate infusion, is associated with the least interventions needed to maintain maternal systolic blood pressure (SBP) within 20% of baseline. METHODS: Women undergoing elective cesarean delivery were randomly allocated to receive placebo or prophylactic phenylephrine infusion at 25, 50, 75, or 100 µg/min immediately after spinal anesthesia in combination with a 2-L fluid coload. Maternal SBP was maintained within the target range using a predetermined algorithm. The number of physician interventions, hemodynamic performance, intraoperative nausea and vomiting, and umbilical cord blood gases were compared among the groups. RESULTS: One hundred one patients were included in the analysis. There were no differences between the placebo and phenylephrine groups in the number of interventions needed to maintain maternal SBP within the target range. Doses of phenylephrine of 25 and 50 µg/min were associated with significantly fewer interventions when compared with 100 µg/min (P = 0.004 vs 50 µg/min, P = 0.02 vs 25 µg/min). Predelivery hypotension was more frequent in the control group compared with all phenylephrine groups. Phenylephrine 75 and 100 µg/min groups were associated with a significantly higher incidence of predelivery hypertension compared with control (P < 0.001 vs 75 µg/min and 100 µg/min). There was a trend toward an increase in median magnitude of deviations of SBP above or below baseline (P = 0.006), and the bias of SBP to be above baseline (P < 0.001) with increasing rates of phenylephrine infusion. There were no differences in the incidence and severity of intraoperative nausea and vomiting and umbilical cord blood gases among the groups. CONCLUSIONS: The use of prophylactic fixed rate phenylephrine infusions did not significantly reduce the number of physician interventions needed to maintain maternal predelivery SBP within 20% of baseline compared with placebo. However, prophylactic phenylephrine infusions reduced the incidence and severity of maternal predelivery hypotension. Phenylephrine 25 and 50 µg/min administered as a prophylactic fixed rate infusion provided greater maternal hemodynamic stability than phenylephrine 75 and 100 µg/min. Prophylactic fixed rate infusions may have limited application in clinical practice, and future studies assessing the accuracy of hemodynamic control with variable rate phenylephrine infusions are needed.


Assuntos
Agonistas alfa-Adrenérgicos/administração & dosagem , Raquianestesia , Pressão Sanguínea/efeitos dos fármacos , Cesárea , Hipotensão/terapia , Fenilefrina/administração & dosagem , Raquianestesia/efeitos adversos , Antieméticos/uso terapêutico , Dióxido de Carbono/sangue , Cesárea/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Procedimentos Cirúrgicos Eletivos , Feminino , Sangue Fetal/metabolismo , Humanos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Infusões Parenterais , Estimativa de Kaplan-Meier , Oxigênio/sangue , Efeito Placebo , Gravidez , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
17.
Front Physiol ; 11: 900, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32792990

RESUMO

Preterm premature rupture of membranes is a leading cause of preterm births. Cytokine induced matrix metalloproteinase1 and interleukin 8 production from amnion mesenchymal cells may contribute to fetal membrane weakening and rupture. Progestins inhibit inflammation induced fetal membrane weakening but their effect on the inflammatory response of amnion mesenchymal cells is unknown. This study was designed to determine the role of progesterone receptor membrane component 1 and the glucocorticoid receptor in mediating the effects of progestins on interleukin-1ß induced matrix metalloproteinase 1 and interleukin-8 expression in human amnion mesenchymal cells. Primary amnion mesenchymal cells harvested from human fetal membranes were passaged once and treated with vehicle, progesterone or medroxyprogesterone acetate at 10-6 M for 1 h followed by stimulation with interleukin-1ß at 1 ng/ml for 24 h. Medroxyprogesterone acetate but not progesterone inhibited interleukin-1ß-induced interlukin-8 and matrix metalloproteinase 1 mRNA expression. In subsequent dose response studies, medroxyprogesterone acetate, but not progesterone, at doses of 10-6-10-8 M inhibited interleukin-1ß induced interleukin-8 and matrix metalloproteinase 1 mRNA expression. We further demonstrated that inhibition of glucocorticoid receptor expression, but not progesterone receptor membrane component 1 knockdown with small interfering RNA transfection, resulted in a reversal in medroxyprogesterone acetate's (10-7 M) inhibition of interleukin-1ß- induced matrix metalloproteinase 1 mRNA expression and interleukin-8 mRNA expression and protein expression. Our findings demonstrate that medroxyprogesterone acetate exerts its anti-inflammatory effect primarily through the glucocorticoid receptor in human amnion mesenchymal cells. Modulation of glucocorticoid receptor signaling pathways maybe a useful therapeutic strategy for preventing inflammation induced fetal membrane weakening leading to preterm premature rupture of membranes.

18.
J Thromb Haemost ; 18(8): 1813-1838, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32356929

RESUMO

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are point-of-care viscoelastic devices that use whole blood samples to assess coagulation and fibrinolysis. These devices have been studied extensively in cardiac surgery, but there is limited robust evidence supporting its use in obstetrics. The hesitancy toward its routine use in obstetrics may be due to the current lack of randomized controlled trials and large observational studies. The study aims to systematically review studies that investigated TEG/ROTEM use in pregnancy or peripartum, and to provide recommendations for future studies to fill current research gaps. We performed a systematic review of studies on viscoelastic testing in obstetrics. Included studies were original research, used TEG or ROTEM during pregnancy or peripartum, and published in English. Ninety-three studies, spanning 31 years from 1989 to 2020 and with a total of 32,817 participants, were included. Sixty-two (66.7%) of the studies used TEG and 31 (33.3%) used ROTEM. To date, there are a total of two randomized controlled trials on TEG/ROTEM use in obstetrics. ROTEM may be used to guide transfusion therapy for postpartum hemorrhage. TEG and ROTEM can detect the hypercoagulable changes associated with pregnancy. Variability between study protocols and results suggests the need for future large prospective high-quality studies with standardized protocols to investigate the utility of TEG/ROTEM in assessing risk for thrombosis and hemorrhage as well as in guiding prophylaxis and treatment in obstetric patients. This review identifies the gaps and provides concrete recommendations for future studies to fill those gaps.


Assuntos
Transtornos da Coagulação Sanguínea , Obstetrícia , Transfusão de Sangue , Feminino , Humanos , Gravidez , Estudos Prospectivos , Tromboelastografia
19.
Front Physiol ; 11: 687, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655414

RESUMO

Premature preterm rupture of membranes (PPROM), rupture of fetal membranes before 37 weeks of gestation, is the leading identifiable cause of spontaneous preterm births. Often there is no obvious cause that is identified in a patient who presents with PPROM. Identifying the upstream molecular events that lead to fetal membrane weakening presents potentially actionable mechanisms which could lead to the identification of at-risk patients and to the development of new therapeutic interventions. Functional genomic studies have transformed understanding of the role of gene regulation in diverse cells and tissues involved health and disease. Here, we review the results of those studies in the context of fetal membranes. We will highlight relevant results from major coordinated functional genomics efforts and from targeted studies focused on individual cell or tissue models. Studies comparing gene expression and DNA methylation between healthy and pathological fetal membranes have found differential regulation between labor and quiescent tissue as well as in preterm births, preeclampsia, and recurrent pregnancy loss. Whole genome and exome sequencing studies have identified common and rare fetal variants associated with preterm births. However, few fetal membrane tissue studies have modeled the response to stimuli relevant to pregnancy. Fetal membranes are readily adaptable to cell culture and relevant cellular phenotypes are readily observable. For these reasons, this is now an unrealized opportunity for genomic studies isolating the effect of cell signaling cascades and mapping the fetal membrane responses that lead to PPROM and other pregnancy complications.

20.
Curr Med Res Opin ; 36(6): 1025-1032, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32212939

RESUMO

Objectives: Childhood asthma is a common chronic illness that has been associated with mode of delivery. However, the effect of cesarean delivery alone does not fully account for the increased prevalence of childhood asthma. We tested the hypothesis that neuraxial anesthesia used for labor analgesia and cesarean delivery alters the risk of developing childhood asthma.Methods: Within the Newborn Epigenetics Study birth cohort, 196 mother and child pairs with entries in the electronic anesthesia records were included. From these records, data on maternal anesthesia type, duration of exposure, and drugs administered peripartum were abstracted and combined with questionnaire-derived prenatal risk factors and medical records and questionnaire-derived asthma diagnosis data in children. Logistic regression models were used to evaluate associations between type of anesthesia, duration of anesthesia, and the development of asthma in males and females.Results: We found that longer duration of epidural anesthesia was associated with a lower risk of asthma in male children (OR = 0.80; 95% CI = 0.66-0.95) for each hour of epidural exposure. Additionally, a unit increase in the composite dose of local anesthetics and opioid analgesics administered via the spinal route was associated with a lower risk of asthma in both male (OR = 0.59, 95% CI = 0.36-0.96) and female children (OR 0.26, 95% CI 0.09-0.82).Conclusion: Our data suggest that peripartum exposure to neuraxial anesthesia may reduce the risk of childhood asthma primarily in males. Larger human studies and model systems with longer follow-up are required to elucidate these findings.


Assuntos
Anestesia Epidural/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Asma/etiologia , Epigênese Genética , Adulto , Cesárea/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Gravidez , Estudos Retrospectivos
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