Enhanced recovery after fetal spina bifida surgery: what is our global practice?

OBJECTIVE: Prenatal spina bifida closure results in improved outcomes for the child compared to postnatal surgery but is associated with significant maternal morbidity. Optimization of the perioperative care for women who underwent fetal spina bifida surgery could improve maternal and pregnancy outcomes. Enhanced Recovery After Surgery (ERAS) protocols are multimodal, evidence-based care plans that have been adopted for multiple surgical procedures to promote faster and better patient recovery and shorter hospitalization. This study aims to explore if fetal centers have implemented ERAS principles in this setting. Furthermore, we provide recommendations for the perioperative management of patients undergoing fetal spina bifida surgery. METHODS: Fifty-three fetal therapy centers offering prenatal surgery for open spina bifida were identified and invited to complete a digital questionnaire covering their pre-, intra- and postoperative management. An overall score was calculated per center based on the center's compliance with 20 key ERAS principles, extrapolated from ERAS guidelines for cesarean section, gynecologic oncology and colorectal surgery. Each item was scored 1 or 0 when the center did or did not comply with each principle, with a maximum score of 20. RESULTS: The questionnaire was completed by 46 centers in 17 countries (response rate 87%). Twenty-two centers (48%) exclusively perform open fetal surgery (laparotomy and hysterotomy), whereas 14 (30%) offer both open and fetoscopic procedures and 10 (22%) use fetoscopy only. The perioperative management of patients undergoing fetoscopic and open surgery was highly similar. The median ERAS score was 12 (mean 12.5, SD 2.4, range 8-17). Center compliance was the highest for the use of regional anesthesia (98%), avoidance of bowel preparation (96%), and thromboprophylaxis (96%), while the lowest compliance was achieved for preoperative carbohydrate loading (15%), postoperative nausea and vomiting prevention (33%), avoidance of overnight fasting (33%) and a 2-hour fasting period for clear fluids (20%). ERAS scores were similar in centers with a short (2-5 days), medium (6-10 days) and long (≥11 days) hospital stay (12.8 ± 2.4, 12.1 ± 2.0, and 10.3 ± 3.2, respectively, p=0.15). Furthermore, there was no significant association between ERAS score and surgical technique or center volume. CONCLUSION: The perioperative management of fetal spina bifida surgery is highly variable across fetal therapy centers worldwide. Standardizing protocols according to ERAS principles may improve patient recovery, reduce maternal morbidity, and shorten hospital stay after fetal spina bifida surgery. This article is protected by copyright. All rights reserved.

Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens.

Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 µg; carbetocin 100 µg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 µg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 µg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 µg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 µg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.

The association of shock index and haemoglobin variation with postpartum haemorrhage after vaginal delivery: a prospective cohort pilot study.

INTRODUCTION: Shock index and continuous non-invasive haemoglobin monitoring (SpHb) have both been proposed for the timely recognition of postpartum haemorrhage (PPH). We sought to determine, in parallel, the association of each of shock index and SpHb with blood loss after vaginal delivery. METHODS: Sixty-six women were recruited to this prospective observational study. Shock index and SpHb were recorded postpartum for 120 min. The association between each of shock index and SpHb with quantitative blood loss (QBL) at 30, 60 and 120 min postpartum was determined using linear mixed models. Area-under-the-receiver-operator-characteristic (AUROC) curves were constructed to evaluate the diagnostic ability of shock index and SpHb to detect PPH (defined as QBL ≥1000 mL). RESULTS: Shock index trend was associated with QBL over the first 30 min (r=0.37, P=0.002), but not over 60 or 120 min. There was an association of SpHb trend with QBL over the first 30 min (P=0.06), but not over 60 min (r=-0.32, P=0.009) or 120 min (r=-0.26, P=0.03). Maximum shock index within 60 min correlated with QBL (r=0.54, P <0.001) and was a predictor of PPH (P=0.0012, AUROC 0.796). Maximum change in SpHb within 60 min negatively correlated with QBL (r=-0.4, P <0.001) and was a predictor of PPH (P=0.048, AUROC 0.761). CONCLUSIONS: The trend of shock index and its peak values are associated with blood loss after vaginal delivery and are early indicators of PPH. Negative trend of SpHb is a late sign of PPH and has a weaker association with blood loss than shock index.

Oxytocin at elective caesarean delivery: a dose-finding study in women with obesity.

Prophylactic oxytocin administration at the third stage of labour reduces blood loss and the need for additional uterotonic drugs. Obesity is known to be associated with an increased risk of uterine atony and postpartum haemorrhage. It is unknown whether women with obesity require higher doses of oxytocin in order to achieve adequate uterine tone after delivery. The purpose of this study was to establish the bolus dose of oxytocin required to initiate effective uterine contraction in 90% of women with obesity (the ED90 ) at elective caesarean delivery. We conducted a double-blind dose-finding study using the biased coin up-down design method. Term pregnant women with a BMI ≥ 40 kg.m-2 undergoing elective caesarean delivery under regional anaesthesia were included. Those with conditions predisposing to postpartum haemorrhage were not included. Oxytocin was administered as an intravenous bolus over 1 minute upon delivery of the fetus. With the first woman receiving 0.5 IU, oxytocin doses were administered according to a sequential allocation scheme. The primary outcome measure was satisfactory uterine tone, as assessed by the operating obstetrician 2 minutes after administration of the oxytocin bolus. Secondary outcomes included the need for rescue uterotonic drugs, adverse effects and estimated blood loss. We studied 30 women with a mean (SD) BMI of 52.3 (7.6) kg.m-2 . The ED90 for oxytocin was 0.75 IU (95%CI 0.5-0.93 IU) by isotonic regression and 0.78 IU (95%CI 0.68-0.88 IU) by the Dixon and Mood method. Our results suggest that women with a BMI ≥ 40 kg.m-2 require approximately twice as much oxytocin as those with a BMI < 40 kg.m-2 , in whom an ED90 of 0.35 IU (95%CI 0.15-0.52 IU) has previously been demonstrated.

Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women.

Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of carbetocin using a biased coin up-and-down design in women with a body mass index ≥ 40 kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of carbetocin was estimated as 62.9 (95%CI 57.0-68.7) µg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) µg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for carbetocin in obese women at elective caesarean section is lower than the dose of 100 µg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8 µg in women with body mass index < 40 kg.m-2 .

International consensus statement on the use of uterotonic agents during caesarean section.

It is routine to give a uterotonic drug following delivery of the neonate during caesarean section. However, there is much heterogeneity in the relevant research, which has largely been performed in low-risk elective cases or women with uncomplicated labour. This is reflected in considerable variation in clinical practice. There are significant differences between dose requirements during elective and intrapartum caesarean section. Standard recommended doses are higher than required, with the potential for acute cardiovascular adverse effects. We recommend a small initial bolus dose of oxytocin, followed by a titrated infusion. The recommended doses of oxytocin may have to be increased in women with risk factors for uterine atony. Carbetocin at equipotent doses to oxytocin has similar actions, while avoiding the requirement for a continuous infusion after the initial dose and reducing the need for additional uterotonics. As with oxytocin, carbetocin dose requirements are higher for intrapartum caesarean sections. A second-line agent should be considered early if oxytocin/carbetocin fails to produce good uterine tone. Women with cardiac disease may be very sensitive to the adverse effects of oxytocin and other uterotonics, and their management needs to be individualised.

Uterotonic drug usage in Canada: a snapshot of the practice in obstetric units of university-affiliated hospitals.

OBJECTIVE: The objective of this study was to determine the pattern of uterotonic drug usage in obstetric units of university-affiliated hospitals in Canada. METHODS: This was a prospective observational study conducted in the form of an electronic survey. The target group consisted of chiefs or directors of Obstetrics and Anaesthesia at university-affiliated hospitals across Canada. The survey was sent out between November 2016 and January 2017, using the program 'SurveyMonkey'. Data on institutional obstetric practices and usage of uterotonic agents were collected. RESULTS: The survey was sent to 92 obstetricians and anesthesiologists from 46 institutions, of which 33 clinicians from 24 institutions responded. About 65% of clinicians were unaware of the rate of postpartum hemorrhage in their institution. The first-line agent for vaginal deliveries was reported as oxytocin by 94% and carbetocin by 6% of physicians. For women at low-risk for postpartum hemorrhage when undergoing cesarean deliveries (CD), 66% reported oxytocin as the first-line uterotonic, while 34% reported carbetocin. For CDs at high-risk of postpartum hemorrhage, 60% of physicians reported oxytocin and 40% reported using carbetocin initially. The use of second-line uterotonics was also variable. The choice of uterotonic was mainly based on perceived efficacy and Society of Obstetricians and Gynaecologists of Canada guidelines. CONCLUSION: There is a lack of a unified approach to the use of uterotonic drugs for postpartum hemorrhage management in Canada. To improve the management of postpartum hemorrhage due to uterine atony, an evidence-based approach to usage and consensus between obstetricians and anesthesiologists is warranted.

Uterotonics in elective caesarean delivery: a randomised non-inferiority study comparing carbetocin 20 µg and 100 µg.

Postpartum haemorrhage is the leading cause of maternal mortality worldwide and prophylactic uterotonic drug administration after the delivery of the infant is advised. Carbetocin is recommended as an uterotonic, but the minimum effective dose has not been verified. We compared the efficacy of two doses of intravenous carbetocin (20 µg and 100 µg) in women undergoing elective caesarean delivery. This was a randomised, double-blind, non-inferiority study in women at low risk of postpartum haemorrhage. Carbetocin was administered on delivery of the anterior shoulder of the neonate. Uterine tone was assessed by the obstetrician 2 min and 5 min after carbetocin administration according to an 11-point numerical rating scale (0 = atonic uterus and 10 = firm uterus). The primary outcome was uterine tone 2 min after carbetocin administration. The pre-specified non-inferiority margin was 1 point on the 11-point scale. Secondary outcomes included: uterine tone at 5 min; use of additional uterotonics within 24 h; blood loss; and adverse effects. Data were available for 53 women in the carbetocin-20 group and for 55 women in the carbetocin-100 group. The mean (SD) uterine tone at 2 min was 7.5 (1.9) in the carbetocin-20 group and 8.0 (1.5) in the carbetocin-100 group. The lower limit of the one-sided 95%CI for the mean difference was outside the non-inferiority margin (at -1.1; p = 0.11) meaning non-inferiority of carbetocin 20 µg compared with carbetocin 100 µg could not be confirmed. However, the secondary outcome measures of uterine tone at 5 min, blood loss and use of additional uterotonics were similar in both groups.

Gastric ultrasound in the third trimester of pregnancy: a randomised controlled trial to develop a predictive model of volume assessment.

Bedside gastric ultrasonography can be performed reliably by anaesthetists to assess gastric content in the peri-operative period. We aimed to study the relationship between gastric cross-sectional area, assessed by ultrasound, and volumes of clear fluids ingested by pregnant women. We recruited 60 non-labouring third-trimester pregnant women in a randomised controlled and assessor-blinded study. A standardised scanning protocol of the gastric antrum was performed in the 45° semirecumbent and 45° semirecumbent-right lateral positions. Subjects were randomly allocated to drink one out of six predetermined volumes of apple juice (0 ml, 50 ml, 100 ml, 200 ml, 300 ml, 400 ml). Qualitative and quantitative assessments at a baseline period after an 8-h fast, and immediately after the drink, were used to establish the correlation between antral cross-sectional area and volume ingested. A predictive model to estimate gastric volume was developed. Antral cross-sectional area in the semirecumbent right lateral position significantly correlated with the ingested volume (Spearman rank correlation = 0.7; p < 0.0001). A cut-off value of 9.6 cm2 discriminated ingested volumes ≥ 1.5 ml.kg-1 with a sensitivity of 80%, a specificity of 66.7%, and an area under the curve of 0.82. A linear predictive model was developed for gastric volume based only on antral cross-sectional area (Volume (ml) = -327.1 + 215.2 × log (cross-sectional area) (cm2 )). We conclude that in pregnant women in the third trimester of gestation, the antral cross-sectional area correlates well with volumes ingested, and this cut-off value in the semirecumbent right lateral position discriminates high gastric volumes.

Interrater reliability of qualitative ultrasound assessment of gastric content in the third trimester of pregnancy.

BACKGROUND: Pulmonary aspiration of gastric contents in pregnant women undergoing general anaesthesia is one of the most feared complications in obstetric anaesthesia. Bedside gastric ultrasonography is a feasible imaging tool to assess the gastric content. The purpose of this study was to investigate the reliability of qualitative bedside assessment of the gastric content performed by anaesthesiologists on third trimester pregnant women. METHODS: Pregnant women (≥32 weeks gestational age) were randomized to undergo ultrasound (US) assessments of their stomach in a fasting state (>8 h), or after ingestion of clear fluids only, or solid food. Three anaesthesiologists trained in gastric ultrasonography performed the assessments using a low-frequency curved-array US transducer (5-2 MHz). Primary outcome of the study was the consistency of raters in diagnosing the correct status of the gastric content, which was used to determine the interrater reliability among the three anaesthesiologists. Secondary outcomes were overall proportion of correct and incorrect diagnoses and the specific proportions of correct diagnosis across the three gastric content groups. RESULTS: We analysed 32 pregnant women. The interrater reliability displayed a kappa statistic of 0.74 (bias corrected 95% CI: 0.68-0.84). The overall proportion of correct diagnosis was 87.5% (84 of 96). The odds of correct diagnosis for 'solid contents' were 16.7 times the odds for 'empty', and 14.3 times for 'clear fluid'. CONCLUSIONS: Our results show the consistency of the qualitative US assessment of gastric contents of pregnant women in the third trimester by anaesthesiologists. A kappa of 0.74 suggests substantial agreement in terms of interrater reliability for this diagnostic measurement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01564030.

Breastfeeding success rate after vaginal delivery can be high despite the use of epidural fentanyl: an observational cohort study.

BACKGROUND: Epidural labor analgesia inclusive of high-dose fentanyl has been thought to affect breastfeeding in multiparous patients. In our experience, this effect is not as significant as quoted in the literature. This study was designed to evaluate breastfeeding success in women receiving epidural analgesia with fentanyl-containing solutions at our institution. METHODS: Term multiparous women who received epidural analgesia for labor, had previously breastfed, and who intended to breastfeed, were recruited. Baseline demographics, as well as detailed epidural, obstetric and neonatal data, were collected. Epidural analgesia was achieved with a mixture of bupivacaine and fentanyl. Subjects were telephoned both 1 and 6 weeks after delivery, and a breastfeeding questionnaire was completed. Our primary outcome was breastfeeding cessation at 6 weeks. RESULTS: One hundred and five women were recruited, with 18 exclusions. The median cumulative epidural fentanyl dose was 151.4 microg (30-570 microg). No neonates developed complications attributable to labor analgesia. Four women stopped breastfeeding because of issues related to the baby (4.6%); only one of them received a fentanyl dose >150 microg. The breastfeeding success rate was therefore >95%. The women had a median maternity leave of 12 months, and 69% received post-partum lactation support. CONCLUSIONS: The incidence of successful breastfeeding in multiparous women who undergo vaginal delivery with epidural analgesia inclusive of fentanyl is much greater at our institution than previously reported in the literature. This may be due to favorable conditions such as time off work and post-natal support.

Unintentional subdural catheter placement during labor analgesia shows typical radiological pattern but atypical response to the Tsui test.

Subdural injection may be associated with abnormally extensive or limited spread of local anesthetics during neuraxial anesthesia. This complication is difficult to diagnose clinically. Radiological imaging is the gold standard for confirming the location of subdural catheter, but electrical stimulation of the catheter has also been described as a useful diagnostic tool. We present the case of an obstetric patient with unintentional subdural catheter placement that presented as a failed epidural block associated with severe upper back and scapular pain on catheter injection. Electrical stimulation of the catheter did not elicit muscle contractions until a current of 4 mAmp was attained, which is the response pattern of epidural placement. Subdural location of the catheter was subsequently confirmed by contrast radiography. This case adds to the evidence that subdural catheters are difficult to identify clinically, and that electrical stimulation may not differentiate them from epidural catheters.

ED95 of phenylephrine to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery.

BACKGROUND: The purpose of this trial was to determine the 95% effective dose (ED95) of phenylephrine by intermittent i.v. bolus, to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery. METHODS: The study was conducted in a double-blinded fashion in 50 patients undergoing elective cesarean delivery under spinal anesthesia. The dose of phenylephrine was determined using up-down sequential allocation, modified by a variation of the Narayana rule. Systolic pressure and heart rate were assessed every minute until uterine incision. The first patient was assigned a 40-microg dose, and the dose to subsequent patients varied by 10-microg increments or decrements. An adequate response was defined as absence of hypotension (systolic pressure <80% of baseline) and nausea. The study solution was given immediately after spinal administration, without prior pressure measurement, and thereafter when the systolic pressure was 120% of baseline) was observed in 14 cases, immediately after intrathecal injection and prophylactic phenylephrine administration in all cases. CONCLUSION: The ED95 of phenylephrine, administered as intermittent boluses to prevent pre-delivery spinal-induced hypotension and/or nausea at elective cesarean delivery, is at least 122 microg (lower limit of the confidence interval). The safety of this dose warrants further studies.

Oxytocin-ergometrine co-administration does not reduce blood loss at caesarean delivery for labour arrest.

OBJECTIVE: To determine if intravenous infusion of a combination of oxytocin and ergometrine maleate is better than oxytocin alone to decrease blood loss at caesarean delivery for labour arrest. DESIGN: Prospective, double-blinded, randomised controlled trial. SETTING: Mount Sinai Hospital, Toronto, Canada. POPULATION: Women undergoing caesarean deliveries for labour arrest. METHODS: Forty-eight women were randomised to receive infusion of either ergometrine maleate 0.25 mg + oxytocin 20 iu or oxytocin 20 iu alone, diluted in 1 l of lactated Ringer's Solution, immediately after delivery of the infant. Unsatisfactory uterine contractions after delivery were treated with additional boluses of the study solution or rescue carboprost. Blood loss was estimated based on the haematocrit values before and 48 hours after delivery. MAIN OUTCOME MEASURES: The primary outcome was the estimated blood loss, while the secondary outcomes included the use of additional uterotonics, need for blood transfusion and the incidence of adverse effects. RESULTS: The estimated blood loss was similar in the oxytocin-ergometrine and oxytocin-only groups; 1218 +/- 716 ml and 1299 +/- 774 ml, respectively (P = 0.72). Significantly fewer women required additional boluses of the study drug in the oxytocin-ergometrine group (21 and 57%; P = 0.01). Nausea (42 and 9%; P = 0.01) and vomiting (25 and 4%; P = 0.05) were significantly more prevalent in the oxytocin-ergometrine group. CONCLUSIONS: In women undergoing caesarean delivery for labour arrest, the co-administration of ergometrine with oxytocin does not reduce intraoperative blood loss, despite apparently superior uterine contraction.

Determination of the ED95 for intrathecal plain bupivacaine combined with fentanyl in active labor.

BACKGROUND: Combined spinal-epidural (CSE) analgesia is an effective technique for pain control in labor and is particularly useful in the active phase. Excessive doses of intrathecal bupivacaine may be associated with adverse effects. This study is designed to estimate the ED95 for intrathecal plain bupivacaine with fentanyl 15 microg in labor. METHODS: Forty healthy women in active labor (cervical dilatation > or = 5 cm and verbal numeric pain score > or = 6/10) were given CSE for labor analgesia with intrathecal plain bupivacaine and fentanyl 15 microg. The initial dose of bupivacaine was 1.75 mg. Doses were varied in a 0.25-mg testing interval according to a method of sequential allocation designed to cluster the dose around the ED95. Effectiveness was defined as a verbal numeric pain score < or = 1 within 10 min of intrathecal injection. RESULTS: There was a 100% response rate to the 1.75-mg dose (95% CI 84.6-100.0%) and an 85.0% response rate to 1.50 mg (95% CI 64.0-95.8%). The ED95 for intrathecal plain bupivacaine with fentanyl 15 microg in active labor was 1.66 mg (95% CI 1.50-482.5 mg). The incidence of fetal bradycardia was 7.5%. The incidence of pruritus was 55%. No patient experienced motor block. CONCLUSIONS: This is the first dose-finding study specifically designed to estimate the ED95 of intrathecal bupivacaine combined with a fixed amount of fentanyl for analgesia in active labor. The combination of bupivacaine 1.75 mg with fentanyl 15 microg rapidly and reliably alleviated pain in the active phase of labor.

Complications of neuraxial anesthesia in an extreme morbidly obese patient for Cesarean section.

A morbidly obese patient presented for elective cesarean section. This case demonstrates the technical difficulties and potentially life-threatening complications encountered in attempting to locate an epidural space at a distance of over 11 cm from the skin. Ultrasound was used to aid in locating the space. The resources required and the logistical problems that impact on staff members in managing a morbidly obese patient presenting for cesarean section are also highlighted.