Uterotonics, magnesium sulphate and antibiotics during childbirth and peripartum: Important obstetric drugs for the anaesthesiologist.

The main causes of maternal mortality are comorbidities, hypertensive pregnancy syndrome, obstetric haemorrhage, and maternal sepsis. For this reason, uterotonics, magnesium sulphate, and antibiotics are essential tools in the management of obstetric patients during labour and in the peripartum period. These drugs are widely used by anaesthesiologists in all departments, and play a crucial role in treatment and patient safety. For the purpose of this narrative review, we performed a detailed search of medical databases and selected studies describing the use of these drugs in patients during pregnancy, delivery and the pospartum period. Uterotonics, above all oxytocin, play an important role in the prevention and treatment of pospartum haemorrhage, and various studies have shown that in obstetric procedures, such as scheduled and emergency caesarean section, they are effective at lower doses than those hitherto accepted. We also discuss the use of carbetocin as an effective alternative that has a therapeutic advantage in certain clinical circumstances. Magnesium sulphate is the gold standard in the prevention and treatment of eclampsia, and also plays a neuroprotective role in preterm infants. We describe the precautions to be taken during magnesium administration. Finally, we discuss the importance of understanding microbiology and the pharmacology of antibiotics in the management of obstetric infection and endometritis, and draw attention to the latest trends in antibiotic regimens in labour and caesarean section.

Isolation of lactic acid bacteria from the reproductive tract of mares as potentially beneficial strains to prevent equine endometritis.

Endometritis, the inflammation of the endometrium, is the leading cause of subfertility in mares, and therefore responsible for major economic losses in the horse industry worldwide. It is generally treated with uterine lavages combined with ecbolic agents and local or systemic antibiotics. However, since antibiotic overuse has been associated with antimicrobial resistance in mares with persistent endometritis, new prevention and treatment alternatives are needed. One such alternative could be the use of probiotic lactic acid bacteria (LAB) isolated from the host. Thanks to their species specificity, resident microbiota may restore ecological equilibrium within the host, and therefore, help prevent infections and improve physiological functions. In the present study, 257 bacterial strains were isolated from 77 healthy mares, and 88.76% (n = 228) of them were phenotypically classified as LAB. Within this group, 65.79% were able to inhibit at least one strain from each of the genera that most commonly cause equine endometritis (Streptococcus equi subsp. zooepidemicus, Escherichia coli, and Staphylococcus spp.). Five strains (RCE11, RCE20, RCE91, RCE99, and RCE167) were selected on the basis of their beneficial properties: ability to autoaggregate and adhere to equine epithelial cells, high inhibition of and co-aggregation with all the bacteria isolated from clinical cases of endometritis evaluated, and negative co-inhibition between one another. All five were finally identified as Enterococcus spp., namely E. faecium (two strains), E. hirae (two strains), and E. gallinarum (one strain). Further studies will assess their safety and biotechnological potential for the design of a multi-strain probiotic formula to prevent equine endometritis.

Addition of clinoptilolite in the diet reduces uterine PMN leukocytes and open days in multiparous lactating dairy cows managed in a mountain tropical pasture-based system.

This study aimed to assess the effect of adding clinoptilolite in the diet on uterine health and reproductive performance in multiparous lactating dairy cows managed in a tropical pasture-based system above 2500 m of altitude. Seventy-seven multiparous Holstein crossbred cows from two farms were allocated randomly into two groups: clinoptilolite supplemented cows (CLG, n = 42) and non-supplemented cows as control (CG, n = 35). Cows from CLG were supplemented with clinoptilolite from 30 days (50 g/cow/day) before to 60 days after calving (200 g/cow/day). In CLG cows, percentages of uterine PMN leukocytes (P < 0.0001) and proportion of subclinical endometritis (P = 0.0187) were lower than in CG. The interval calving to first corpus luteum was shorter (P = 0.0759) in CLG than CG, and calving to first service interval was similar between treatments. Cows from CLG became pregnant 35 days earlier than CG cows (P = 0.0224). On farm A, calving to conception interval was 18.1 days longer in CLG than in CG (P = 0.3750); in farm B, this interval was 86.2 days shorter in CLG than in CG (P = 0.0002). In conclusion, daily addition of clinoptilolite in the diet decreased the percentage of uterine PMN leukocytes, the proportion of cows with subclinical endometritis, and shortened the calving-conception interval in multiparous lactating dairy cows.

Proteomics of endometrial fluid after dexamethasone treatment in mares susceptible to endometritis.

Corticotherapy is a common treatment in mares susceptible to endometritis. Isoflupredone improves pregnancy rates and affects the protein profile of endometrial fluid in comparison to untreated mares. Dexamethasone decreases postbreeding fluid accumulation and uterine edema; however, its effects on the protein profile of the endometrial fluid have not yet been studied. The aim of the present study was to verify the effect of dexamethasone on the protein profile of endometrial fluid, in the presence or absence of infection, from mares susceptible to persistent postbreeding endometritis. Nine susceptible mares aged between 7 and 18 years were used. After checking for signs of estrus, mares were subjected to four treatments: C: mares received no treatment and served as control; D: mares received 40-mg dexamethasone at breeding, with collection of samples after 6 hours; I-6 and I-24: intrauterine infusion of 1 × 10(9)Streptococcus zooepidemicus/mL and samples collected after 6 and 24 hours; I/D-6 and I/D-24: intrauterine infusion of 1 × 10(9)S zooepidemicus/mL and 40-mg dexamethasone, collecting the sample after 6 and 24 hours. All mares were subjected to all treatments. Samples were collected and subjected to two-dimensional electrophoresis and mass spectrometry for the identification of relevant protein spots. Corticotherapy altered the protein profile of the endometrial fluid of susceptible mares, characterized by an increase and/or decrease in the optical density of inflammatory acute-phase proteins. We conclude that the use of dexamethasone in mares with and without infection alters the protein profile of endometrial fluid of susceptible mares.

Strategies for the treatment of dairy cows at high risk for postpartum metritis and for the treatment of clinical endometritis in Argentina.

The objectives of this study were to evaluate the efficacy of (1) administering ceftiofur hydrochloride in dairy cows with calving-related disorders to prevent metritis and (2) a combination of GnRH and PGF2α for the treatment of clinical endometritis, under Argentinean dairy farming conditions. Cows at high risk (HRC) for metritis (dystocia, RFM >12 h postpartum, hypocalcaemia, twins, or stillbirth) were randomly assigned to receive either 1.1 mg/Kg of ceftiofur hydrochloride on three consecutive days (HRC treated group HRCT, n = 110) or remained untreated (HRC control group HRCC, n = 126). Cows with low risk (LRC, no calving-related disorders, n = 868) did not receive any treatment (LRC group, n = 868). All cows were examined for metritis between days 4 and 10 and for clinical endometritis between 24 and 30 days postpartum. The body condition score (BCS) was recorded at both examinations. Cows with endometritis at days 24 to 30 postpartum received either 1.5 mg of D-cloprostenol (PGF; n = 129) or 100 µg of GnRH followed by D-cloprostenol after 7 days (GnRH+PGF, n = 119). There was no overall effect of treatment on the incidence of metritis or on time to pregnancy. Treatment, however, reduced the incidence of metritis in cows with high BCS (HRCT = 24.0 %, HRCC = 38.5 %) but had no effect in cows with low BCS (HRCT = 38.7 %, HRCC = 37.5 %). The proportion of pregnant cows by days in milk was greater (P < 0.01) in LRC group compared with that of the HRCT and HRCC groups. No significant differences were found between groups PG and PG+GNRH. GnRH+PGF treatment, however, tended (P = 0.06) to increase pregnancy rate in cows with a moderate loss of BCS (76.5 vs 65.2 %) but tended to reduce pregnancy rate (54.5 vs 76.0 %) in cows with a more pronounced loss in BCS (>0.75 points).

[Comparison of maternal and perinatal outcomes in the conservative treatment preterm premature membrane rupture between the use of erythromycin and clindamycin]. / Comparación de resultados maternos y perinatales en el tratamiento conservador de la rotura prematura de membranas pretérmino entre el uso de eritromicina y clindamicina.

BACKGROUND: premature rupture of membranes occurs between 5 and 15% of pregnancies, of these, 10% occurs at term and preterm 2 to 3.5%. OBJECTIVE: To compare maternal and perinatal outcomes from the use of erythromycin or clindamycin in women with preterm premature rupture of membranes with conservative treatment at the Regional General Hospital No. 36. PATIENTS AND METHODS: comparative, prospective, randomized study conducted at the Regional General Hospital No. 36 of the Instituto Mexicano del Seguro Social, Puebla. The most common risk factors were cervical infections (55%) and urinary tract infection (55%). A history of premature rupture of membranes in pregnancy was reported in 12.5% of patients. Group A was prescribed erythromycin and group B, standard-dose clindamycin, these were the independent variables. Maternal outcomes (deciduoendometritis and chorioamnionitis) and perinatal (respiratory distress syndrome, necrotizing enterocolitis and sepsis) were the dependent variables. Fisher exact test was applied to the results of the study. RESULTS: about perinatal outcome, sepsis was expressed more frequently in the clindamycin group (60%) compared with erythromycin (35%). The occurrence of respiratory distress syndrome was similar in both groups, 70 and 75% respectively. For necrotizing enterocolitis, 25 and 5%. Maternal alterations as chorioamnionitis occurred in 20% of patients in group A and 5% in group B. Endometritis results were similar in both groups. CONCLUSIONS: comparing the maternal and perinatal outcomes with conservative management of premature rupture of membranes, results were better in the group treated with erythromycin. It is not possible to prove it statistically because of the sample size.

Enrofloxacin-based therapeutic strategy for the prevention of endometritis in susceptible mares.

Enrofloxacin (EFX) is often used empirically to prevent uterine infections in mares in order to improve efficiency on Commercial Embryo Transfer Farms. This study investigated the uterine distribution of EFX and its metabolite ciprofloxacin (CFX) in mares and assessed the minimal inhibitory concentrations (MIC) of EFX against various common pathogens as a basis for establishing a rational dosing schedule. Plasma and uterine pharmacokinetic (PK) studies were performed in two groups (n = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg/kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (beta-haemolytic streptococci) ranged from 0.25-2 and 1.5-3.0 microg/mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg/kg respectively. After i.v. treatment with EFX at 5 mg/kg, endometrial concentrations of EFX and CFX above the MIC value were detected for 36-48 and 22-43 h posttreatment for Gram-negative and -positive isolates respectively. Concentrations above MIC were maintained for much shorter periods at the lower (2.5 mg/kg) treatment dose. Based on these results, a conventional dose (5 mg/kg) of EFX given prebreeding followed by two further doses at 36-48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis.

Immune parameters in mares resistant and susceptible to persistent post-breeding endometritis: effects of immunomodulation.

Our objective was to characterize immune parameters in susceptible (SM) and resistant (RM) mares, with and without artificial insemination (AI) and immunomodulation. Eight RM and eight SM were selected based on their reproductive history and functional tests. Both groups of mares were evaluated during three consecutive cycles: Cycle 1, untreated cycle (control); Cycle 2, AI with dead semen; Cycle 3, AI with dead semen and immunomodulation. Endometrial biopsies were taken during the three cycles as follows: Cycle 1--at estrus, when follicles > or =35mm and at diestrus (7+/-1 days after ovulation); Cycle 2--at estrus 24h post-AI, and at diestrus; Cycle 3--at estrus 24h after treatment with a Mycobacterium phlei cell-wall extract (MCWE) and AI, and at diestrus. The mRNA transcription (mRNAT) of IL-8 and IL-10 were determined by real-time PCR. Image analysis of immunohistochemistry slides was performed using digital software (Image-Pro Plus v 5.0; Media Cybernetics); the percentage of stained area was determined for Major Histocompatibility Complex II (MHC-II), polymorphonuclear leukocytes (PMN) and T lymphocytes (TL) on each tissue section. In Cycle 1, SM had significantly higher MHC-II, TL, PMN and IL-8 than RM during estrus (P<0.006, P<0.0005, P<0.05, respectively), while transcription of IL-10 was significantly lower than in RM (P<0.0001). During diestrus, SM had higher levels of TL, PMN and IL-8 than RM (P<0.0001). After AI (Cycle 2), SM had higher levels of IL-8 and lower levels of IL-10 than RM at estrus and no differences were detected for MHC-II, TL and PMN positive cells. During diestrus in the same cycle, all the immune parameters were higher in SM mares (P<0.005, P<0.0004, P<0.0001, P<0.02, respectively). When MCWE was applied at the time of AI (Cycle 3), SM expressed significant higher levels of IL-10 24h after treatment (P<0.005), which were also higher than in the control Cycle 2 or after AI (Cycle 2). However, no significant differences were detected for MHC-II, lymphocytes-PMN or IL-8 between SM and RM during diestrus in Cycle 3. This study showed that SM had higher levels of all immune parameters except IL-10 than RM during Cycle 1. After AI (Cycle 2), the inflammatory condition persisted in SM but not RM mares until day 7 post-ovulation. Following treatment with MCWE at the time of AI (Cycle 3) uterine immunological changes in SM resulted in an endometrial immune environment similar to that found in normal RM.

Probiotic properties of vaginal lactic acid bacteria to prevent metritis in cattle.

AIMS: The isolation of bovine vaginal lactic acid bacteria (LAB) and the screening of their beneficial properties to select those that could be used as probiotics in the prevention of bovine metritis were performed. METHODS AND RESULTS: Out of 76 Lactobacillus sp. and seven Streptococcus sp. strains, a small number showed high- and medium hydrophobicity when the microbial adhesion to hydrocarbons method (MATH) was applied. In the agar plate diffusion test, a large number of strains inhibited vaginal bovine Escherichia coli 99/14 and human E. coli. This inhibition was due to acid. Only a few strains inhibited Actinomyces pyogenes 96/393, a pathogen isolated from bovine metritis. This inhibition remained after neutralization. The taxonomic identification of the selected strains was carried out by an amplified ribosomal DNA restriction analysis (ARDRA). Most of the strains were identified as Lactobacillus fermentum, a few as Lactobacillus gasseri and one as Lactobacillus rhamnosus. CONCLUSIONS: Bovine vaginal lactobacilli strains have differential surface properties. The strains selected are capable of inhibiting specific metritis pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results can be applied for future studies to design a probiotic product to prevent metritis in dairy postpartum cows.

Reducing infections among women undergoing cesarean section in Colombia by means of continuous quality improvement methods.

BACKGROUND: Improving obstetric care in resource-limited countries is a major international health priority. OBJECTIVE: To reduce infection rates after cesarean section by optimizing systems of obstetric care for low-income women in Colombia by means of quality improvement methods. METHODS: Multidisciplinary teams in 2 hospitals used simple methods to improve their systems for prescribing and administering perioperative antibiotic prophylaxis. Process indicators were the percentage of women in whom prophylaxis was administered and the percentage of these women in whom it was administered in a timely fashion. The outcome indicator was the surgical site infection rate. RESULTS: Before improvement, prophylaxis was administered to 71% of women in hospital A; 24% received prophylaxis in a timely fashion. Corresponding figures in hospital B were 36% and 50%. Systems improvements included implementing protocols to administer prophylaxis to all women and increasing the availability of the antibiotic in the operating room. These improvements were associated with increases in overall and timely administration of prophylaxis (P<.001) in both hospitals by time series analysis, with adjustment for volume and case mix. After improvement, overall and timely administration of prophylaxis was 95% and 96% in hospital A and 89% and 96% in hospital B. In hospital A, the surgical site infection rate decreased immediately after the improvements (P<.001). In hospital B, the infection rate began a downward trend before the improvements that continued after their implementation (P =.04). CONCLUSION: Simple quality improvement methods can be used to optimize obstetric services and improve outcomes of care in resource-limited settings.

La revisión uterina posparto: ¿factor de riesgo para infección puerperal

Ante la elevada tasa de infección puerperal (2.5 a 6.9 por ciento) evidenciada en el Instituto Materno Infantil (IMI), en los años 1996 a 1997 y dentro del programa de mejoramiento de calidad para disminuir la tasa de infección materna y perinatal del Instituto, realizamos un estudio analítico, retrospectivo de cohortes de pacientes expuestas a revisión uterina comparándolas con aquellas a las cuales no se les realizó. Se incluyeron todas las pacientes que tuvieron parto vaginal en el IMI, durante el perído comprendido entre el 1 de septiembre de 1996 y el 28 de febrero de 1997, excepto aquellos con diagnóstico de corioamnionitis. El antecedente de revisión uterina estuvo presente en el 38.6 por ciento de las pacientes que presentaron infección uterina puerperal y en el 27.9 por ciento de las pacientes que no presentaron esta complicación (RR:1.62 IC 95 por ciento 1.23 - 2.16). Teniendo en cuenta que las pacientes con ruptura prematura de mambranas de mas de 12 horas y las pacientes con parto pretérmino podrían tener una deciduoendometritis subclínica, se hizo un segundo análisis encontramos que el riesgo relativo de desarrollar infección uterina puerperal teniendo como factor de riesgo la revisión uterina fue de 1,83 (IC 95 por ciento 1,37 - 2,44). Esta evaluación inicial determinó que hay yna asociación entre la revisión manual de la cavidad uterina y la infección uterina puerperal; por lo cual justificamos la realización de un estudio prospectivo, controlando los factores de confusión que podrían influir en los resultados

Prevention of postcesarean infectious morbidity with a single dose of intravenous metronidazole.

The efficacy of intravenous metronidazole for the prevention of postcesarean section infectious morbidity was studied in 100 healthy women, randomly given either the drug or a placebo. The metronidazole group received 1.0 g intravenously, immediately after cord clamping. Among the 50 patients who received metronidazole, endometritis developed in 7 (14%) as it did in 15 (30%) of the placebo group (P less than 0.01); wound infection was found in 1 (2%) and 4 (8%), respectively (P less than 0.01). If both infectious complications are compared together, the difference (16% versus 38%) is more significant (P less than 0.001). Metronidazole was well tolerated by the mother and with this type of administration regimen, the fetus is not exposed to the drug. It is concluded that metronidazole, used as here reported, is effective in reducing the frequency of postcesarean section endometritis and wound infection with the consequent clinical and economic impacts.

Profilaxis antibiótica en cesáreas / Antibiotics prophilaxis in cesarean section

En un estudio prospectivo de pacientes sin evidencia de infección, que fueron cesareadas, se evaluó la morbilidad infecciosa postoperatoria. En un grupo se administró ampicilina por 8.8 días, en un segundo grupo se usó ampicilina en el perioperatorio y un tercer grupo no recibió antibiótico. Las complicaciones infecciosas postoperatorias (endometritis, infección de herida operatoria, infección urinaria, pelviperitonitis), fueron significativamente menos frecuentes en las pacientes en quienes se usó antibiótico profiláctico preoperatorio que en los otros 2 grupos. Se observó resistencia a la ampicilina de los gérmenes que se logró cultivar. Por tanto, en nuestro Hospital sería recomendable el uso preoperatorio de la ampicilina o bien no usar ningún antibiótico profiláctico en la mujer cesareada, por sus efectos secundarios y por las desventajas y peligros del uso indiscriminado de la ampicilina

Antibiótico-profilaxis en la ruptura prematura de membranas / Antibiotic-profilactic in the premature rupture of membranes

Siendo la ruptura prematura de membranas un problema obstétrico de relativa frecuencia, que conlleva un aumento de la morbilidad materna; se realizó el presente estudio de carácter prospectivo para evaluar la antibioticoprofilaxis en él. Se seleccionó a 40 gestantes a término que presentaba R.P.M. y que cumplieran los requisitos del protocolo; así la mitad de ellas recibieron una asociación de antibióticos de los tipos ampicilina/cloxacilina o dicloxacilina de acuerdo a la vía de administración, la otra mitad no recibió ningún tipo de antibióticos. A todas las pacientes, antes de admitirlas, se les verificó el R.P.M., se les tomó muestras del líquido amniótico para el cultivo de gérmenes aerobios y anaerobios, hemograma, numeración, fórmula y sedimento urinario, en caso de sospecha de endometritis post-parto, se tomaba cultivo de loquios, además de otras pruebas pertinentes. Al finalizar el estudio, apreciamos que con la antibioticoprofilaxis, no se presentó morbilidad materna en ningún caso. Además parecería corroborarse que el líquido amniótico ejerce acción bacteriostática en los gérmenes, porque llama la atención que los cultivos de las muestras tomadas del líquido amniótico fueron negativos en la totalidad de los casos a pesar de que algunas pacientes presentaron R.P.M. de 68 y 88 horas, y otras presentaron endometritis post-parto, comprobados con cultivos de loquios.

Prophylactic cefoxitin in cesarean section.

The effectiveness of prophylactic cefoxitin in preventing postcesarean section infection was studied in a high risk population. One hundred women were evaluated, and on a random double-blind basis 50 received placebo and 50 received cefoxitin. There were three doses of drug given intravenously, either placebo or 1 gram of cefoxitin at the time of cord clamping and again four and eight hours later. Those receiving cefoxitin had significantly less postoperative infections, fewer had bacteremia and there was less postoperative fever as measured by the fever index. The patient with the most protracted infection in this study received cefoxitin. Problems with the use of systemic antibiotic prophylaxis in preventing postcesarean section infection are discussed. Cefoxitin is an effective agent to use in patients undergoing cesarean section who are at high risk for infection.