Sufentanil for carboprost-induced adverse reactions during cesarean delivery under combined spinal-epidural anesthesia.

OBJECTIVES: Carboprost plays an important role in managing refractory uterine atony and severe postpartum hemorrhage. However, it is associated with challenging adverse reactions. We aimed to evaluate the clinical effects of low dose sufentanil on the prevention of adverse events associated with carboprost during cesarean delivery. MATERIAL AND METHODS: Patients were randomly divided into two groups: a placebo control group (group C, n = 15) that received an intravenous infusion of 1 mL of normal saline 2 min before carboprost and a sufentanil group (group S, n = 15) that received 5 µg of sufentanil. The primary outcome was the incidence of nausea and vomiting following carboprost administration. RESULTS: The incidence of nausea, vomiting, and gastrointestinal discomfort was significantly lower in group S than in group C (p < 0.05). CONCLUSIONS: The prophylactic use of low dose sufentanil reduces the incidence of gastrointestinal side effects caused by carboprost administration during cesarean section.

Efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss: A meta-analysis of randomized controlled trials.

Motherwort (YiMuCao), a traditional Chinese herb, has been shown beneficial effects for women's diseases. This meta-analysis aimed to evaluate the efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang from their inception to December 2017. Randomized controlled trials that determined the add-on effects of motherwort injection to carboprost for prevention of post-partum blood loss were eligible. Pooled risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were used to summarize the effect sizes. Eight trials including 1276 pregnant women fulfilled the inclusion criteria. Prophylactic use of motherwort injection add-on therapy significantly reduced the post-partum 2 h (MD -127.5 mL; 95% CI -149.13 to -105.88) and 24 h (MD -146.85 mL; 95% CI -179.77 to -113.94) blood loss and incidence of post-partum hemorrhage (RR 0.28; 95% CI 0.17-0.45) than carboprost. Moreover, adjunctive treatment with motherwort injection significantly decreased the length of the third stage of labor (MD -3.41 min; 95% CI -4.33 to -2.49) and duration of lochia (MD -7.13 days; 95% CI -8.49 to -5.76). There was no statistical significant difference in the incidence of adverse events (RR 0.76; 95% CI 0.50-1.16). Prophylactic use of motherwort injection add-on therapy to carboprost tromethamine could reduce post-partum blood loss. However, more well-designed trials are necessary to confirm the findings of this study due to the methodological flaws of the included trials.

Use of Antihypertensive Medications and Uterotonics During Delivery Hospitalizations in Women With Asthma.

OBJECTIVE: To estimate whether the diagnosis of asthma is associated with the use of specific uterotonic and antihypertensive medications during delivery hospitalizations. METHODS: We used Perspective, an administrative database, to determine whether women hospitalized for delivery complicated by postpartum hemorrhage or preeclampsia received uterotonics and antihypertensive medications differentially based on the absence or presence of asthma from 2006 to 2015. Given that carboprost and intravenous (IV) labetalol may be associated with asthma exacerbation, adjusted models for receipt of these medications were created with adjusted risk ratios with 95% CIs as measures of effect. Risk for status asthmaticus based on receipt of carboprost and IV labetalol was analyzed. RESULTS: Over the study period, a total of 5,691,178 women were analyzed, of whom 239,915 (4.2%) had preeclampsia and 139,841 postpartum hemorrhage (2.5%). Carboprost was used less frequently in patients with asthma compared with patients with no asthma (11.4% vs 18.0%) in comparison with IV labetalol, which was used more commonly when a diagnosis of asthma was present (18.5% vs 16.7%). In unadjusted analysis, the presence of asthma was associated with a 37% decrease in likelihood of carboprost use and an 11% increase in likelihood of labetalol use. In adjusted analysis, the presence of asthma was associated with a 32% decrease in likelihood of carboprost use (adjusted risk ratio 0.68, 95% CI 0.62-0.74) compared with a 7% decrease in labetalol use (adjusted risk ratio 0.93, 95% CI 0.90-0.97). Risk for status asthmaticus was significantly increased with use of IV labetalol compared with other antihypertensive medications (6.5 vs 1.7/1,000 delivery hospitalizations, P<.01). CONCLUSION: There may be an opportunity to reduce use of ß-blockers and carboprost among patients with asthma. Given their association with status asthmaticus, these drugs should be used cautiously in women with asthma.

Uterotonic Medications: Oxytocin, Methylergonovine, Carboprost, Misoprostol.

Uterine atony is a common cause of primary postpartum hemorrhage, which remains a major cause of pregnancy-related mortality for women worldwide. Oxytocin, methylergonovine, carboprost, and misoprostol are commonly used to restore uterine tone. Oxytocin is the first-line agent. Methylergonovine and carboprost are both highly effective second-line agents with severe potential side effects. Recent studies have called into question the effectiveness of misoprostol as an adjunct to other uterotonic agents, but it remains a useful therapeutic in resource-limited practice environments. We review the current role these medications play in the prevention and treatment of uterine atony.

Large doses of uterotonic drugs caused type II second degree sinoatrial block during cesarean section.

In China, it is a routine procedure to inject 250 µg of hemabate (sterile solution, an oxytocic, contains the tromethamine salt of the (I5S)-15 methyl analogue of naturally occurring prostaglandin F2α in a solution suitable for intramuscular injection) into the myometrium of patients experiencing uterine inertia after delivery, with an additional dose given in the event that the efficacy is not obvious. Although hemabate is prohibited from being used in patients with active liver disease, there are no restrictions regarding the application of hemabate in positive hepatitis B surface antigen (HbsAg)-positive subjects with normal liver function. Here we report adverse effects of hemabate in 1 HbsAg-positive subject with normal liver function. This subject experienced increased blood pressure, chest tightness, and type II second degree sinoatrial block 25 minutes after an additional injection of hemabate. Thus, special attention should be paid when applying hemabate in HbsAgpositive subjects with normal liver function.

REFRACTORY BRADYCARDIA--A RARE COMPLICATION OF CARBOPROST TROMETHAMINE FOR INDUCTION OF ABORTION

We report a first case of refractory several-hour sinus bradycardia, a rare but already described side effect of intramuscular administration of carboprost tromethamine to induce abortion for medical indication in a patient without cardiovascular and other diseases. After administration of atropine sulfate 3x0.5 mg intravenously without effect, the patient's sinus rhythm spontaneously normalized as carboprost was eliminated from the body (it has a 3-hour half-life). It is reasonable to believe that the specific prostaglandin underlay the etiology of bradycardia.

A randomized controlled trial of prophylactic sublingual misoprostol versus intramuscular methyl-ergometrine versus intramuscular 15-methyl PGF2alpha in active management of third stage of labor.

OBJECTIVE: To compare the efficacy and side effects of 0.2 mg methyl-ergometrine IM, 400 microg misoprostol sublingual and 125 microg 15 methyl PGF2alpha IM in active management of third stage of labor. METHOD: Two hundred low risk pregnant women with induced or spontaneous labor were randomized to receive either 400 microg misoprostol sublingually or 0.2 mg methyl-ergometrine intramuscularly or 125 microg 15-methyl PGF2alpha intramuscularly, after the delivery of anterior shoulder of baby. The main outcome measures were: blood loss more than 500 ml, need for additional oxytoxic drug, change in hemoglobin level and side effects due to drugs. RESULTS: The median estimated blood loss, blood loss more than 500 ml, need for additional oxytocic drug and change in hemoglobin levels were similar in all three groups. The significant side effects in the misoprostol group were shivering, pyrexia (temperature > 38 degrees C) and vomiting, which were self-limiting. Diarrhea was significantly more in the 15 methyl PGF2alpha group. Three women in methyl-ergometrine group underwent manual removal of placenta. One woman in misoprostol group received blood transfusion. CONCLUSION: Sublingual misoprostol appears to be as effective as intramuscular methyl-ergometrine and intramuscular 15-methyl PGF2alpha in the prevention of postpartum hemorrhage. It can be a good alternative in resource poor setting.

[Clinical study on prevention of postpartum hemorrhage of cesarean section using hemabat in high risk pregnant women].

OBJECTIVE: To observe the effect and safety of hemabat (H) on prevention of postpartum hemorrhage in cesarean section and after cesarean section in high risk pregnant women. METHODS: Four hundred and sixty-nine pregnant women with high hemorrhagic risk factors including twin pregnancy, polyhydramnios, fetal macrosomia, placenta previa were planned cesarean section. A total of 457 pregnant women were divided into 3 groups by operation indications. There were 239 cases of fetal macrosomia, 145 cases of twin pregnancy and polyhydramnios, and 73 cases of placenta previa. Three kinds of hysterotonics were used randomly in each group. Group oxytocin (O): 20 U oxytocin injected into the uterine plus 20 U oxytocin intravascularly, 152 women; Group oxytocin + hemabate (O + H): 20 U oxytocin and 250 microg hemabat injected into the uterine, 192 women; group H: 250 microg hemabat, injected into the uterine, 125 women. The amount of bleeding during the operation and within 2-hour after delivery were measured. The side effect of each group was observed. RESULTS: The amount of bleeding during cesarean section in group O was (445 +/- 262) ml, in group O + H (332 +/- 218) ml, and in group H (375 +/- 265) ml. There was an extremely significant difference between group O and group O + H (P < 0.01). The amount of bleeding within 2 hours after delivery in group O was (176 +/- 193) ml, in group O + H was (110 +/- 114) ml, and in group H was (124 +/- 103) ml. There was a significant difference between groups O, O + H and H. Among the 469 women, 31 had total amount of bleeding more than 1000 ml during operation and within 2 hours after delivery. 48% (15 women) were in group O, 23% in group O + H and 29% in group H. The total amount of bleeding in group O was much more than group O + H and group H in the group of fetal macrosomia (P < 0.01, P < 0.01). Similar results were found in the group of twin pregnancy and polyhydramnios (P < 0.01, P < 0.01). The total amount bleeding in group O + H was much less than group O in the group of placenta previa (P < 0.05). There were 5% (12) pregnant women whose total amount of bleeding was >/= 1000 ml in the group of fetal macrosomia, 8% (11) in the group of twin pregnancy, 11% (8) in the group of placenta previa. No hysterectomy was done among the women. The incidence of side effects in the three groups was 2.6%, 11.5% and 7.0% respectively. Vomiting was frequently seen in the latter two groups, but recovered soon without treatment. CONCLUSION: Hemabat can significantly reduce the amount of bleeding during the cesarean section in pregnant women with high hemorrhagic risk factors and can be used with oxytocin as firstline medicine to prevent hemorrhage during and after delivery.

[Pulmonary edema related to administration of 15-methyl-prostaglandin F2alpha during a cesarean section]. / Edema pulmonar en una cesárea relacionado con la administración de 15-metil prostaglandina F2alpha.

An 18-year-old woman pregnant at 37 weeks gestation and with a history of recurrent urinary tract infection was admitted with a clinical picture of pyelonephritis that responded favorably to antibiotic treatment. After 2 days, cervical ripening was induced with prostaglandin E2 gel and labor was induced with oxytocin. The patient requested epidural analgesia. Six hours after induction, cesarean delivery was indicated owing to risk of fetal distress. The operation was carried out under epidural anesthesia with 10 mL of 0.5% bupivacaine without a vasoconstrictor. After delivery, uterine atony was treated unsuccessfully with oxytocin and methylergometrine maleate; the obstetrician then gave an intramyometrial injection of 0.25 mg of 15-methyl-prostaglandin F2alpha (PGF2alpha). After 5 minutes, SpO2 fell to 89%, accompanied by dyspnea and sinus tachycardia of 130-140 beats/min, with normal cardiorespiratory sounds. The patient was transferred to the postoperative recovery unit, where a chest radiograph led to a diagnosis of acute pulmonary edema. Treatment to reduce edema was successful. PGF2alpha and its analogs are useful for treating uterine atony that does not respond to other drugs, but side effects are not unknown. Caution in prescribing PGF2alpha and care in monitoring the patient's reaction are therefore recommended during and after anesthesia. Unnecessary overhydration should be avoided.

A prospective randomised trial to compare the efficacy and safety of hemabate and syntometrine for the prevention of primary postpartum haemorrhage.

In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.

[The use of prostaglandins in atonic uterine hemorrhages following vaginal delivery]. / Prilozhenie na prostaglandini pri atonichni matochni kruvotecheniia sled vaginalno razhdane.

The authors examine the results of usage of Prostin 15M (Upjohn) in series of 19 women with hypotonic uterine bleeding after vaginal delivery. For the same period (1997) 1179 deliveries were performed in the Department of Obstetrics and Gynecology in HMS-Plovdiv. Positive effect was noted in 16 of the cases (84.22%). Unsatisfactory effect was marked in 3 of the cases--15.78%. Three of the women demonstrated adverse reactions after application of Prostin 15M.

Second-trimester uterine evacuation: A comparison of intra-amniotic (15S)-15-methyl-prostaglandin F2alpha and intravaginal misoprostol.

OBJECTIVE: Our purpose was to compare the efficacy, safety, and adverse effects of intra-amniotically administered (15S)-15-methyl-prostaglandin F(2alpha) and intravaginally administered misoprostol for second-trimester uterine evacuation. STUDY DESIGN: Fifty-one patients were randomly assigned to receive either a single 2.5-mg intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2)(alpha) (n = 26) or two 200-microg intravaginal doses of misoprostol (n = 25) at 12-hour intervals. The primary outcome measured was evacuation of the uterus within 24 hours. RESULTS: The mean time from initiation of termination to uterine evacuation was less in the prostaglandin group than in the misoprostol group (17.5 +/- 8.6 hours vs 22.3 +/- 12.5 hours), but this was not statistically significant (P >.05). The rate of successful fetal evacuation at 24 hours was significantly higher in the prostaglandin group than in the misoprostol group (88% vs 60%, P =.02). The complete-abortion rate and the incidence of adverse effects were similar in both groups. CONCLUSION: The use of an intra-amniotic injection of (15S)-15-methyl-prostaglandin F(2alpha) for midtrimester pregnancy termination is safe and is associated with a greater number of successful uterine evacuations within 24 hours, without an increase in adverse effects, than intravaginal administration of misoprostol.

A comparative study of the efficacy and safety of synthetic prostaglandin E2 derivative and 15-methyl prostaglandin F2 alpha in the termination of midtrimester pregnancy.

A comparative study of a synthetic prostaglandin E2 (PGE2) derivative and 15-methyl prostaglandin F2 alpha (PGF2 alpha) in the termination of midtrimester pregnancy of 13-20 weeks of gestation by intramuscular route, showed 97.5% success rate in both the groups but in comparison to 15-methyl PGF2 alpha which produced severe side-effects eg. diarrhoea and vomiting, synthetic PGE2 derivative had minimal or no side-effects.

Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2 alpha or intravaginal prostaglandin E2 suppositories: a randomized trial.

OBJECTIVE: To compare intramuscular (IM) prostaglandin 15 methyl-F2 alpha (15M-PGF2 alpha) with prostaglandin E2 (PGE2) vaginal suppositories for second-trimester abortion in terms of efficacy and side effects. METHODS: Fifty-one women were randomized to receive either 15M-PGF2 alpha IM injections or PGE2 intravaginal suppositories for second-trimester abortion. Efficacy and side effects of the two agents were analyzed by two-tailed t tests, chi 2 analysis with Fisher exact test, and survival analysis. RESULTS: The mean times to rupture of membranes, delivery of fetus, and delivery of placenta were significantly less for women receiving PGE2 vaginal suppositories. The cumulative abortion rate after 24 hours for the PGE2 group was 96%, compared with 69% for the 15M-PGF2 alpha group. Although there were few differences in side effects, the 15M-PGF2 alpha group had significantly fewer headaches, fevers, and chills. CONCLUSION: Intravaginal PGE2 is superior to IM 15M-PGF2 alpha for second-trimester abortion.

A prospective, double-blind, randomized comparison of prophylactic intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, and intravenous oxytocin, 20 units, for the control of blood loss at elective cesarean section.

OBJECTIVE: Our purpose was to compare intramyometrial 15-methyl prostaglandin F2 alpha with intravenous oxytocin for controlling blood loss at elective cesarean section. STUDY DESIGN: A double-blind, randomized trial was performed with intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, or intravenous oxytocin, 20 U, in 60 women undergoing elective lower segment cesarean section at 36 to 41 weeks' gestation. Subjective assessment of the operative blood loss and early lochial discharge and objective change in hemoglobin and hematocrit before and 24 hours after delivery and the incidence of side effects were compared by nonparametric statistical tests. RESULTS: The mean estimated blood loss was similar in both groups, with 645 ml (SD 278, range 400 to 1500) in the 15-methyl prostaglandin F2 alpha group compared with 605 ml (SD 303, range 200 to 1750) in the oxytocin group. The mean fall in hemoglobin and hematocrit was greater in the 15-methyl prostaglandin F2 alpha group than in the oxytocin group, 0.98 gm/dl (SD 0.95) versus 0.65 gm/dl (SD 0.79) for hemoglobin and 2.58% (SD 2.96) versus 2% (SD 2.96) for hematocrit. None of these differences reached statistical significance. There were no differences in side effects and lochial discharge between the treatment groups. In both groups there was a decrease of approximately 1% in maternal arterial oxygen saturation. CONCLUSION: Routine intramyometrial 15-methyl prostaglandin F2 alpha, 125 micrograms, does not offer any obvious advantage over intravenous oxytocin, 20 U, in reducing operative blood loss at elective lower-segment cesarean section.

Carboprost trometamol in the management of the third stage of labor.

OBJECTIVE: To compare carboprost trometamol with methylergometrine in managing the third stage of labor. METHOD: One hundred and fifty parturient women were randomly assigned to use carboprost trometamol or methylergometrine immediately after delivery. RESULT: Both the duration of the third stage and the mean blood loss were significantly less in the carboprost group than the methergine group (P < 0.001). CONCLUSION: Carboprost trometamol is a more potent uterotonic drug than methylergometrine. Reducing blood loss in parturient women is very important especially in cases where there is the likelihood of anemia.