Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires.

BACKGROUND: Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models. METHODS: In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery. RESULTS: A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain. CONCLUSIONS: The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.

Low-dose aspirin use in the first trimester of pregnancy and odds of congenital anomalies: A meta-analysis of randomized controlled trials.

BACKGROUND: Daily low-dose aspirin (LDA) is recommended in high-risk pregnancies. However, its safety profile in the first trimester has not been well documented. OBJECTIVES: To determine if LDA exposure during the first trimester of pregnancy is associated with higher odds of congenital structural anomalies. SEARCH STRATEGY: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were systematically searched. SELECTION CRITERIA: Randomized controlled trials (RCTs) that assigned participants to LDA (≤150 mg) or placebo/no intervention at less than 14 weeks of pregnancy were eligible. DATA COLLECTION AND ANALYSIS: Random-effects models were performed using the inverse-variance method to calculate pooled effect sizes. Quality of evidence was appraised according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. MAIN RESULTS: Eight RCTs that included 7564 participants assigned to receive daily LDA and 7670 participants that served as controls were analyzed. Low-certainty evidence showed no significant difference in the odds of congenital anomalies (odds ratio 0.87, 95% confidence interval 0.62-1.23, I2  = 0%). CONCLUSIONS: In this meta-analysis, there is no evidence to suggest safety concerns regarding LDA teratogenicity. However, given the overall low quality of evidence, further research (e.g. individual participant data meta-analysis) is needed to confirm LDA safety profile.

External Validation of a Multivariable Prediction Model for Placenta Accreta Spectrum.

BACKGROUND: Placenta accreta spectrum (PAS) is a disorder of abnormal placentation associated with severe postpartum hemorrhage, maternal morbidity, and mortality. Predelivery prediction of this condition is important to determine appropriate delivery location and multidisciplinary planning for operative management. This study aimed to validate a prediction model for PAS developed by Weiniger et al in 2 cohorts who delivered at 2 different United States tertiary centers. METHODS: Cohort A (Brigham and Women's Hospital; N = 253) included patients with risk factors (prior cesarean delivery and placenta previa) and/or ultrasound features of PAS presenting to a tertiary-care hospital. Cohort B (Columbia University Irving Medical Center; N = 99) consisted of patients referred to a tertiary-care hospital specifically because of ultrasound features of PAS. Using the outcome variable of surgical and/or pathological diagnosis of PAS, discrimination (via c-statistic), calibration (via intercept, slope, and flexible calibration curve), and clinical usefulness (via decision curve analysis) were determined. RESULTS: The model c-statistics in cohorts A and B were 0.728 (95% confidence interval [CI], 0.662-0.794) and 0.866 (95% CI, 0.754-0.977) signifying acceptable and excellent discrimination, respectively. The calibration intercept (0.537 [95% CI, 0.154-0.980] for cohort A and 3.001 [95% CI, 1.899- 4.335] for B), slopes (0.342 [95% CI, 0.170-0.532] for cohort A and 0.604 [95% CI, -0.166 to 1.221] for B), and flexible calibration curves in each cohort indicated that the model underestimated true PAS risks on average and that there was evidence of overfitting in both validation cohorts. The use of the model compared to a treat-all strategy by decision curve analysis showed a greater net benefit of the model at a threshold probability of >0.25 in cohort A. However, no net benefit of the model over the treat-all strategy was seen in cohort B at any threshold probability. CONCLUSIONS: The performance of the Weiniger model is variable based on the case-mix of the population with regard to PAS clinical risk factors and ultrasound features, highlighting the importance of spectrum bias when applying this PAS prediction model to distinct populations. The model showed benefit for predicting PAS in populations with substantial case-mix heterogeneity at threshold probability of >25%.

Tranexamic acid administered during cesarean delivery in high-risk patients: maternal pharmacokinetics, pharmacodynamics, and coagulation status.

BACKGROUND: Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1 g intravenous dosing, repeated once after 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk of postpartum hemorrhage may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events, such as thrombosis or renal cortical necrosis. OBJECTIVE: This study aimed to report tranexamic acid pharmacokinetics and pharmacodynamics after 1 g intravenous dosing during cesarean delivery in patients at risk of hemorrhage. The primary endpoint was tranexamic acid plasma concentration of >10 µg/mL, known to inhibit 80% of fibrinolysis. In addition, the correlation between patient demographics and rotational thromboelastometry coagulation changes were analyzed. STUDY DESIGN: In this prospective study, 20 women aged 18 to 50 years, ≥23 weeks of gestation undergoing cesarean delivery with at least 1 major (placenta previa, suspected placenta accreta spectrum, or active bleeding) or 2 minor (≥2 previous cesarean deliveries, previous postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for postpartum hemorrhage were recruited. The exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, previous or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1 g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes and then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations. RESULTS: The median age of participants was 37.5 years (interquartile range, 35.0-39.5), and the median body mass index was 28.6 kg/m2 (interquartile range, 24.9-35.0). The median blood loss (estimated or quantitative) was 1500 mL (interquartile range, 898.5-2076.0). Of note, 9 of 20 (45%) received a transfusion of packed red blood cells. The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8±4.7 µg/mL. All patients had a plasma concentration >10 µg/mL for 1 hour after infusion. Plasma concentration was >10 µg/mL in more than half of the patients at 3 hours and fell <10 µg/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (r=-0.49; 95% confidence interval, -0.77 to -0.07; P=.026). Rotational thromboelastometry EXTEM maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r=0.32; 95% confidence interval, 0.21-0.46; P<.001). EXTEM maximum clot lysis was 0% after infusion in 18 patients (90%), and no patient in the study demonstrated a maximum lysis of >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM clot lysis at 30 minutes and longitudinal tranexamic acid plasma concentrations (r=0.10; 95% confidence interval, -0.20 to 0.19; P=.252). CONCLUSION: After standard 1 g intravenous dosing of tranexamic acid during cesarean delivery in patients at high risk of hemorrhage, a plasma concentration of ≥10 µg/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. The concurrent use of rotational thromboelastometry may demonstrate tranexamic acid's impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.

Placenta Accreta Spectrum Disorders: Knowledge Gaps in Anesthesia Care.

Placenta accreta spectrum (PAS) disorder is a potentially life-threatening condition that can occur during pregnancy. PAS puts pregnant individuals at a very high risk of major blood loss, hysterectomy, and intensive care unit admission. These patients should receive care in a center with multidisciplinary experience and expertise in managing PAS disorder. Obstetric anesthesiologists play vital roles in the peripartum care of pregnant patients with suspected PAS. As well as providing high-quality anesthesia care, obstetric anesthesiologists coordinate peridelivery care, drive transfusion-related decision making, and oversee postpartum analgesia. However, there are a number of key knowledge gaps related to the anesthesia care of these patients. For example, limited data are available describing optimal anesthesia staffing models for scheduled and unscheduled delivery. Evidence and consensus are lacking on the ideal surgical location for delivery; primary mode of anesthesia for cesarean delivery; preoperative blood ordering; use of pharmacological adjuncts for hemorrhage management, such as tranexamic acid and fibrinogen concentrate; neuraxial blocks and abdominal wall blocks for postoperative analgesia; and the preferred location for postpartum care. It is also unclear how anesthesia-related decision making and interventions impact physical and mental health outcomes. High-quality international multicenter studies are needed to fill these knowledge gaps and advance the anesthesia care of patients with PAS.

Anesthetic Management of Von Willebrand Disease in Pregnancy: A Retrospective Analysis of a Large Case Series.

BACKGROUND: Although Von Willebrand disease (vWD) is the most common heritable bleeding disorder, there are limited reports regarding the safety of neuraxial anesthesia in the obstetric population and no definitive guidelines specifying recommended pretreatment or therapies for patients with vWD. The aim of this study is to describe the anesthetic management of pregnant patients with vWD at a large tertiary-care center. METHODS: In this retrospective analysis, the study population was identified from vWD patients evaluated by our high-risk obstetric anesthesia consultation service and by diagnosis codes from our institutional research database registry. We manually reviewed records of patients with vWD in pregnancy who delivered at our institution between January 1, 2000 and January 1, 2019 for demographic characteristics, circumstances of vWD diagnosis, history of bleeding, laboratory studies, and overall management of vWD. Anesthetic management of vWD was at the discretion of individual providers, based on multidisciplinary consensus and the specific circumstances of each patient's disease and obstetric presentation. RESULTS: We identified 106 deliveries among 71 individual vWD patients. Of the unique patients, 54 had vWD type 1, 6 had vWD type 2, and 11 had vWD type unknown. Forty-three cases (40.6%) were cesarean deliveries. Neuraxial techniques were used in 94 of 106 deliveries (88.7%). Treatment with desmopressin or Von Willebrand factor/factor VIII concentrate before neuraxial anesthesia occurred in 27 of 94 neuraxial anesthetics (28.7%). Eleven deliveries (10.4%) were complicated by postpartum hemorrhage (PPH), defined as estimated blood loss of ≥1000 mL. There were no noted adverse anesthetic outcomes (0 of 106; 0% [95% confidence interval, 0-3.4]), including neuraxial hematoma or thromboembolic events. CONCLUSIONS: In this large case series, the majority of vWD patients received neuraxial anesthesia for labor and delivery, with no noted adverse events. This suggests that neuraxial anesthesia can be safely performed with the peripartum management that we describe. Pretreatment was dictated by the type and severity of vWD. Multidisciplinary planning is important to optimize the coagulation status of patients with vWD and facilitate options for analgesia and anesthesia.

The Society for Obstetric Anesthesia and Perinatology Coronavirus Disease 2019 Registry: An Analysis of Outcomes Among Pregnant Women Delivering During the Initial Severe Acute Respiratory Syndrome Coronavirus-2 Outbreak in the United States.

BACKGROUND: Early reports associating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) coronavirus disease 2019 (COVID-19) registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing. METHODS: Deliveries from 14 US medical centers, from March 19 to May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2-infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (eg, delivery mode, hypertensive disorders of pregnancy, and delivery <37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (eg, neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls. RESULTS: One thousand four hundred fifty four peripartum women were included: 490 with SARS-CoV-2 infection (176 [35.9%] symptomatic) and 964 were controls. SARS-CoV-2 patients were slightly younger, more likely nonnulliparous, nonwhite, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery <37 weeks of gestation compared to controls, 73 (14.8%) vs 98 (10.2%) (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.03-2.09). Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2 patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited increases in cesarean delivery (aOR, 1.57; 95% CI, 1.09-2.27), postpartum length of stay (aOR, 1.89; 95% CI, 1.18-2.60), and delivery <37 weeks of gestation (aOR, 2.08; 95% CI, 1.29-3.36). These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia (aOR, 0.52; 95% CI, 0.35-0.75) and more likely to receive general anesthesia for cesarean delivery (aOR, 3.69; 95% CI, 1.40-9.74) due to maternal respiratory failure. CONCLUSIONS: In this large, multicenter US cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.

The interrater reliability and agreement of a 0 to 10 uterine tone score in cesarean delivery.

BACKGROUND: Postpartum hemorrhage is a leading source of maternal morbidity and mortality worldwide with uterine atony identified as the underlying cause in up to 80% of cases. Several measures have been utilized to report uterine tone. The most commonly reported measure is a 0 to 10 numeric rating scale, but this scale has not been tested for reliability or agreement between different raters. OBJECTIVE: The primary purpose of this study was to evaluate the interrater reliability and agreement of the 0 to 10 visual numeric rating scale of uterine tone during cesarean delivery. A secondary purpose was to obtain estimates of scale responsiveness and minimal clinically important difference. STUDY DESIGN: Between August and November of 2018, obstetricians used a 0 to 10 numeric rating score to independently rate uterine tone at 3 and 10 minutes after cesarean delivery by palpation of the uterus. Of note, "0" represented "no tone" and "10" represented excellent tone. Each obstetrician independently and blinded to the other's score pointed to a numeric rating scale held by the anesthesiologist through a clear sterile drape. Intraclass correlation coefficients and Bland-Altman analysis were used to assess interrater reliability and agreement, respectively. Standardized response mean and standard error of measurement were used to obtain estimates of responsiveness and minimal clinically important difference, respectively. RESULTS: A total of 82 and 84 pairs of scores were collected at 3 and 10 minutes, respectively, from pairs of 62 unique obstetricians. The mean±standard deviation difference in scores between rater 1 and rater 2 was 0.4±1.4 at 3 minutes and 0.1±1.1 at 10 minutes. Intraclass correlation coefficients for a future single rater (intraclass correlation coefficient [1, 1]) at 3 and 10 minutes were 0.67 (95% confidence interval, 0.53-0.77) and 0.61 (95% confidence interval, 0.46-0.73), and for the average between 2 future raters (intraclass correlation coefficient [1, 2]), they were 0.80 (95% confidence interval, 0.71-0.87) and 0.76 (95% confidence interval, 0.63-0.84), indicating good and excellent reliability, respectively. Bland-Altman analysis estimated 95% limit of agreement between raters of -2.4 (95% confidence interval, -3.0 to -1.9) to 3.1 (95% confidence interval, 2.6-3.7) at 3 minutes and -2.1 (95% confidence interval, -2.5 to -1.7) to 2.4 (95% confidence interval, 2.0-2.8) at 10 minutes, consistent with good interrater agreement at both time points. The standardized response mean from 3 to 10 minutes after delivery was 1.1 (n=81). Standard error of measurement was 1.0 (95% confidence interval, 0.9-1.1) at 3 minutes and 0.8 (95% confidence interval, 0.7-0.9) at 10 minutes. CONCLUSION: The 0 to 10 numeric rating scale for uterine tone demonstrated good to excellent interrater reliability with 1 and 2 raters, respectively, and good interrater agreement. The scale was responsive to within-parturient change in tone, and preliminary estimates of the minimal clinically important difference were obtained. The 0 to 10 numeric rating scale for uterine tone may be a reliable, standardized tool for future research in reporting degree of uterotonic contraction during cesarean delivery.

Sociodemographic Factors Associated with Request for Labor Epidural Analgesia in a Tertiary Obstetric Hospital in Vietnam.

This study is aimed at examining the sociodemographic factors associated with the utilization of labor epidural analgesia at a large obstetric and gynecology hospital in Vietnam. This was a cross-sectional study of women who underwent vaginal delivery in September 2018 at the Hanoi Obstetrics and Gynecology Hospital. The utilization of epidural analgesia during labor was determined. Univariate and multivariate regression models were applied to evaluate the association between patient demographic and socioeconomic factors and request for labor epidural analgesia. A total of 417 women had vaginal deliveries during the study period. 207 women utilized epidural analgesia for pain relief during labor, and 210 did not. Parturients older than 35 years of age (OR 2.84, 95% CI 1.11-8.17), multiparous women (OR 2.8 95% CI 1.85-4.25), women living from an urban area, women with higher income (OR 6.47, 95% CI 2.59-19.23), and women with higher level of education were more likely to utilize labor epidurals. Factors related to a parturient request for epidural analgesia during labor at our tertiary obstetric hospital included age greater than 35 years, multiparity, and high income and education levels. Educational outreach to women about the benefits of epidural analgesia can target women who do not share these demographic characteristics.

Maternal and umbilical cord procalcitonin, high-sensitivity C-reactive protein, and interleukin-6 levels in preeclamptic and normotensive patients: A cross-sectional study.

OBJECTIVES: To report maternal and umbilical vein levels of procalcitonin (PCT) in patients with preeclampsia (PE) compared to controls. As secondary aims, we measured high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). Moreover, correlation analyses were performed between the inflammatory biomarkers and mean arterial pressure (MAP). STUDY DESIGN: This was a single center, cross-sectional study. MAIN OUTCOME MEASURES: After Institutional Review Board approval and written informed consent, patients with or without PE were enrolled. PCT, hs-CRP, and IL-6 levels were compared between groups using multiple linear regression models. We calculated the adjusted ratios of geometric means (aRGM) for the comparison of patients with and without PE. Correlation analysis between the inflammatory biomarkers and MAP was performed using Spearman's method. RESULTS: A total of 156 participants were enrolled, yielding 156 venous blood samples and umbilical venous blood samples. Seventy-six patients were in the PE group, and 80 patients were in the control group. Maternal plasma and serum concentrations of PCT (aRGM 3.35 (95% confidence interval [CI]: 2.26, 4.95; p < 0.001)), hs-CRP (aRGM 1.85 (95% CI: 1.30, 2.63; p = 0.003)), and IL-6 (aRGM 1.49 (95% CI: 1.08, 2.04; p = 0.045)) were higher in the PE group. In umbilical venous samples, the concentrations of PCT (aRGM 2.54 (95% CI: 1.46, 4.44; p = 0.003)) and hs-CRP (aRGM 1.45 (95% CI: 1.13, 1.87; p = 0.012)) in the PE group were higher than the controls. No difference in umbilical venous IL-6 concentrations were detected between PE vs. control groups (aRGM 1.46; 95% CI: 1.07, 1.98; p = 0.051). There was positive correlation for both PCT and hs-CRP with MAP in maternal and umbilical venous samples. However, there was no correlation between IL and 6 and MAP in maternal or umbilical venous samples. CONCLUSIONS: PCT levels were elevated in maternal and umbilical venous samples of patients with PE, and correlated with disease severity.

The Most Influential Publications in Obstetric Anesthesiology, 1998-2017: Utilizing the Delphi Method for Expert Consensus.

BACKGROUND: There have been many advances in obstetric anesthesiology in the past 2 decades. We sought to create a list of highly influential publications in the field using the Delphi method among a group of obstetric anesthesiology experts to create an important educational, clinical, and research resource. METHODS: Experts in the field, defined as obstetric anesthesiologists selected to present the Gerard W. Ostheimer Lecture at the Society for Obstetric Anesthesia and Perinatology (SOAP) annual meeting within the past 20 years, were recruited to participate. The Delphi technique was used by administering 3 rounds of surveys. Participants were initially asked to identify the highly influential publications from the year they presented the Ostheimer lecture, in addition to the most influential publications from the time period overall. Highly influential publications were defined as those that changed traditional views, invoked meaningful practices, catalyzed additional research, and fostered ideas or practices that had durability over time. After each round of surveys, responses were collected and used as choices for subsequent surveys with the goal of obtaining group consensus. RESULTS: We determined expert consensus on 22 highly influential publications from 1998 to 2017. The focus of these publications ranged from disease entities, interventions, treatment methodologies, and complications. CONCLUSIONS: Key themes in the publications chosen included the reduction of maternal morbidity and mortality and refinements in the analgesic and anesthetic management of labor and delivery.