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Obesity is a worldwide epidemic and is associated with an increased risk of hypertension, diabetes, and obstructive sleep apnea. Pregnant patients with obesity experience a higher risk of maternal and fetal complications. Anesthesia also poses higher risks for obese parturients and may be more technically challenging due to body habitus. Safe anesthesia practice for these patients must take into consideration the unique challenges associated with the combination of pregnancy and obesity.

Background The dural puncture epidural technique may improve analgesia quality by confirming midline placement and increasing intrathecal translocation of epidural medications. This would be advantageous in obese parturients with increased risk of block failure. This study hypothesizes that quality of labor analgesia will be improved with dural puncture epidural compared to standard epidural technique in obese parturients. Methods Term parturients with body mass index greater than or equal to 35 kg · m–2, cervical dilation of 2 to 7 cm, and pain score of greater than 4 (where 0 indicates no pain and 10 indicates the worst pain imaginable) were randomized to dural puncture epidural (using 25-gauge Whitacre needle) or standard epidural techniques. Analgesia was initiated with 15 ml of 0.1% ropivacaine with 2 µg · ml–1 fentanyl, followed by programed intermittent boluses (6 ml every 45 min), with patient-controlled epidural analgesia. Parturients were blinded to group allocation. The data were collected by blinded investigators every 3 min for 30 min and then every 2 h until delivery. The primary outcome was a composite of (1) asymmetrical block, (2) epidural top-ups, (3) catheter adjustments, (4) catheter replacement, and (5) failed conversion to regional anesthesia for cesarean delivery. Secondary outcomes included time to a pain score of 1 or less, sensory levels at 30 min, motor block, maximum pain score, patient-controlled epidural analgesia use, epidural medication consumption, duration of second stage of labor, delivery mode, fetal heart tones changes, Apgar scores, maternal adverse events, and satisfaction with analgesia. Results Of 141 parturients randomized, 66 per group were included in the analysis. There were no statistically or clinically significant differences between the dural puncture epidural and standard epidural groups in the primary composite outcome (34 of 66, 52% vs. 32 of 66, 49%; odds ratio, 1.1 [0.5 to 2.4]; P = 0.766), its individual components, or any of the secondary outcomes. Conclusions A lack of differences in quality of labor analgesia between the two techniques in this study does not support routine use of the dural puncture epidural technique in obese parturients. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. Methods We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery. Results There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml−1 [65] vs 378 pg ml−1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137–0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], –0.196 [–0.256 to –0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels. Conclusions Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.

We conducted an updated systematic review and meta-analysis on maternal outcomes associated with uterine exteriorization compared with in situ repair in women undergoing Cesarean delivery. We searched for randomized controlled trials comparing uterine exteriorization with in situ repair during Cesarean delivery. Primary outcomes were intraoperative nausea and vomiting (IONV) and perioperative decrease in hemoglobin concentration. Secondary outcomes were postoperative nausea and vomiting (PONV), estimated blood loss, fever, endometritis, wound infection, intraoperative and postoperative pain, postoperative analgesic use, duration of surgery and hospital stay, and time to return of bowel function. Twenty studies with 20,909 parturients were included. Exteriorization was associated with higher risk of IONV (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.66 to 2.63; I2 = 0%), with no difference in perioperative hemoglobin concentration decrease (mean difference, − 0.06 g·dL-1; 95% CI, − 0.20 to 0.08; I2 = 97%) compared with in situ repair. There were no significant differences in estimated blood loss, transfusion requirement, PONV, duration of surgery, duration of hospital stay, time to return of bowel function, fever, endometritis, or wound infection. Postoperative pain (incidence of pain graded > 5/10) at six hours (OR, 1.64; 95% CI, 1.31 to 2.03; I2 = 0%) was higher with exteriorization, but there was no difference in need for rescue analgesia (OR, 2.48; 95% CI, 0.89 to 6.90; I2 = 94%) or pain scores at 24 hr compared with in situ repair. In this updated systematic review and meta-analysis, uterine exteriorization was associated with an increased risk of IONV but no significant change in perioperative hemoglobin decrease compared with in situ repair. PROSPERO (CRD42020190074); registered 5 July 2020.

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

Previous studies of obstructive sleep apnea (OSA) risk in gravidas with chronic hypertension (cHTN) did not control for obesity as a risk factor for OSA. We therefore performed this study to evaluate whether OSA is more prevalent among gravidas with cHTN compared to normotensive gravidas matched for body mass index (BMI) and gestational age (primary outcome). We also assessed whether OSA is more severe when comorbid with cHTN in pregnancy (secondary outcome).This was a single-center, prospective cohort study. Adult gravidas at 10-20 weeks of gestation, with and without cHTN, were enrolled and BMI matched. All subjects answered OSA screening questionnaires and underwent a home sleep test when they were between 10 and 20 weeks of gestation. Pregnancy outcomes were followed for all subjects. We performed univariable and multivariable logistic regression to model the relationship between cHTN status and OSA.A total of 100 pregnant subjects (50 with cHTN and 50 normotensive) completed a home sleep test of 2 hours or more. There were no differences in demographic variables between the 2 groups, except that gravidas with cHTN were significantly older than normotensive subjects (mean ± standard deviation [SD] 34 ± 4 vs 30 ± 6 years; P.001). OSA was more prevalent (64% vs 38%; P = .009; odds ratio [95% confidence interval (CI)] 2.90 [1.30-6.65]; P = .01) and more severe in gravidas with cHTN (moderate or severe OSA 59% vs 21%; P = .009). After controlling for age, we found no overall association between cHTN on OSA risk (adjusted odds ratio [95% CI] 2.22 [0.92-5.40]; P = .076). However, among gravidas older than 25 years of age, cHTN was associated with higher odds of OSA (adjusted odds ratio [95% CI], 2.64 [1.06-6.71], P = .038).cHTN and age are important risk factors for OSA in gravidas. Gravidas with cHTN should be screened for OSA in early pregnancy. Future studies may validate screening tools that include cHTN and age, and investigate the role of OSA therapy in blood pressure control.

Objective This study compares the number of units of red blood cells (RBCs) transfused in patients with placenta accreta spectrum (PAS) treated with or without a multidisciplinary algorithm that includes placental uterine arterial embolization (P-UAE) and selective use of either immediate or delayed hysterectomy. Study Design This is a retrospective study of deliveries conducted at a tertiary care hospital from 2001 to 2018 with pathology-confirmed PAS. Those with previable pregnancies or microinvasive histology were excluded. To improve the equity of comparison, analyses were made separately among scheduled and unscheduled cases, therefore patients were assigned to one of four cohorts as follows: (1) scheduled/per-algorithm, (2) scheduled/off-algorithm, (3) unscheduled/per-algorithm, or (4) unscheduled/off-algorithm. Primary outcomes included RBCs transfused and estimated blood loss (EBL). Secondary outcomes included perioperative complications and disposition. Results Overall, 95 patients were identified, with 87 patients meeting inclusion criteria: 36 treated per-algorithm (30 scheduled and 6 unscheduled) and 51 off-algorithm patients (24 scheduled and 27 unscheduled). Among scheduled deliveries, 9 (30.0%) patients treated per-algorithm received RBCs compared with 20 (83.3%) patients treated off-algorithm (p Conclusion A multidisciplinary algorithm including P-UAE and selective use of delayed hysterectomy is associated with a lower rate of blood transfusion in scheduled but not unscheduled cases. Key Points

Background Optimizing analgesia after cesarean delivery is a priority and requires balancing adequate pain relief with the risk of analgesics-associated adverse effects. Current recommendations are for use of a multimodal, opioid-sparing analgesic regimen that includes neuraxial morphine combined with scheduled nonsteroidal anti-inflammatory drugs (NSAIDs) and scheduled acetaminophen. Furthermore, recent studies recommend scheduled acetaminophen with as-needed opioids in lieu of acetaminophen-opioid combination drugs to reduce opioid consumption and optimize analgesia. However, the extent of utilization of this recommended regimen in the United States is unclear. We therefore performed this retrospective study to evaluate postoperative analgesic regimens utilized after cesarean delivery under neuraxial anesthesia, examine variability across institutions, evaluate changes over time in postoperative analgesic practice, and examine factors associated with the use of neuraxial morphine and of multimodal analgesia. Methods This retrospective cohort study was approved by the Duke University Institutional Review Board. Parturients who underwent cesarean delivery under neuraxial anesthesia from 2008 to 2018 were included. Data were extracted from a nationwide inpatient administrative-financial database (Premier Inc, Charlotte, NC) and included parturient characteristics, comorbidities, hospital characteristics, and charges for administered medications. The primary outcome was the postoperative analgesic regimen utilized during hospitalization, including utilization of neuraxial morphine and of multimodal analgesia for postoperative pain control. We also examined the factors associated with the use of neuraxial morphine and of the multimodal regimen incorporating neuraxial morphine, NSAIDs, and acetaminophen. Results Data from 804,752 parturients were analyzed. Of this cohort, 75.8% received neuraxial morphine, 93.2% received NSAIDs, 28.4% received acetaminophen, and 81.3% received acetaminophen-opioid combination drugs. Only 6.1% received the currently recommended regimen of neuraxial morphine with NSAIDs and acetaminophen, with this percentage increasing from 1.3% in 2008 to 15.0% in 2018. On the other hand, 58.9% received neuraxial morphine, NSAIDs, and an acetaminophen-opioid combination drug, with this regimen being utilized in 57.0% of cases in 2008 and 58.1% in 2018. The hospital in which the patient was treated accounted for 54.7% of the variation in receipt of neuraxial morphine and 41.2% in the variation in receipt of multimodal analgesia with neuraxial morphine, NSAIDs, and acetaminophen, with this variability in receipt of neuraxial morphine and of multimodal analgesia being largely independent of patient characteristics. Conclusions Relatively few parturients received the currently recommended multimodal analgesic regimen of neuraxial morphine with NSAIDs and acetaminophen after cesarean delivery. Additionally, the majority received acetaminophen-opioid combination drugs rather than plain acetaminophen. Further studies should investigate the implications for patient outcomes.

The purpose of this article is to provide a summary of the Enhanced Recovery After Cesarean delivery (ERAC) protocol written by a Society for Obstetric Anesthesia and Perinatology (SOAP) committee and approved by the SOAP Board of Directors in May 2019. The goal of the consensus statement is to provide both practical and where available, evidence-based recommendations regarding ERAC. These recommendations focus on optimizing maternal recovery, maternal-infant bonding, and perioperative outcomes after cesarean delivery. They also incorporate management strategies for this patient cohort, including recommendations from existing guidelines issued by professional organizations such as the American College of Obstetricians and Gynecologists and the American Society of Anesthesiologists. This consensus statement focuses on anesthesia-related and perioperative components of an enhanced recovery pathway for cesarean delivery and provides the level of evidence for each recommendation.

To investigate gabapentinoid utilization and association with postoperative pulmonary complications after gynecologic surgery.After Institutional Review Board approval, we performed this retrospective cohort study using the Premier Healthcare Database. We used ICD-10 and charge codes to identify adults who underwent elective gynecologic surgery from 2015 to 2018 and received either gabapentin or pregabalin on the day of surgery. Our primary outcome was a composite of pulmonary complications: respiratory failure, pneumonia, reintubation, pulmonary edema, and non-invasive or invasive ventilation. Secondary outcomes included mortality, intensive care unit admission, mechanical or non-invasive ventilation, hospital length of stay, re-admission within 30 days, opioid consumption and antiemetic use. Multivariable generalized linear mixed models were utilized to examine the associations between gabapentinoids and our outcome measures, adjusted for all covariates.Data from 253,013 patients were analyzed, with 19,121 (7.6%) receiving gabapentinoids. Gabapentinoid utilization increased from 3.9% in 2015 to 12.3% in 2018, and was associated with increased pulmonary complications (OR 1.19; 95% CI 1.03-1.38), non-invasive ventilation (odds ratio [OR] 1.53; 95% CI 1.29-1.81), duration of hospital stay (% change 1.75; 95% CI 0.92-2.59), daily antiemetic doses on day of surgery (mean difference [MD] 1.37; 95% CI 1.26-1.49) and subsequently (MD 1.61; 95% CI 1.30-1.99), and higher daily average (MD 4.59 mg; 95% CI 3.55-5.63) and total (MD 8.74 mg; 95% CI 6.83-10.62) parenteral morphine equivalents.Gabapentinoid utilization in gynecologic surgery is increasing and is associated with postoperative pulmonary complications.

Optimal pain relief requires a balance between adequate analgesia and risk of adverse effects. Opioids remain the cornerstone for managing moderate to severe pain, but are associated with opioid-induced respiratory depression (OIRD) and gastrointestinal complications. Opioids exert their analgesic effects predominantly via G-protein signaling, however, adverse effects including OIRD are mediated by the β-arrestin pathway. Oliceridine is the first of a new class of biased opioid agonists that preferentially activate G-protein signaling over β-arrestin, which would theoretically improve analgesia and reduce the risk of adverse effects. Oliceridine is approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe acute pain. The efficacy of Oliceridine was mainly established in two randomized controlled Phase III clinical trials of patients experiencing moderate to severe pain after bunionectomy (APOLLO-1) and abdominoplasty (APOLLO-2). The results of the APOLLO studies demonstrate that Oliceridine, when administered via patient-controlled analgesia (PCA) demand boluses of 0.35mg and 0.5mg, provides superior analgesia compared to placebo, and is equianalgesic to PCA morphine 1mg demand boluses, without significant difference in the incidence of respiratory complications. In a more pragmatic trial of surgical and non-surgical patients, the ATHENA observational cohort study reported rapid onset of analgesia with Oliceridine given with or without multimodal analgesia. However, these studies were designed to evaluate analgesic efficacy, and it is still uncertain if Oliceridine has a better safety profile than conventional opioids. Although several post hoc analyses of pooled data from the APOLLO and ATHENA trials reported that Oliceridine was associated with lower OIRD and gastrointestinal complications compared to morphine, prospective studies are needed to elucidate if biased agonists such as Oliceridine reduce the risk of adverse effects compared to conventional opioids.

Adequate pain control is a mainstay in enhanced recovery after surgery (ERAS) protocols. ERAS protocols are widely accepted in colorectal and gynecologic surgeries and are increasingly implemented in the obstetric setting. Multimodal analgesia incorporating non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen is a mainstay of ERAS protocols for cesarean delivery, but little research has focused on the choice of NSAIDs or timing of initiation in women undergoing cesarean delivery. At our institution, patients undergoing cesarean delivery receive a standardized multimodal analgesic regimen consisting of neuraxial morphine with NSAIDs and acetaminophen. Our initial protocol involved starting the oral analgesics in the recovery room. There was variability in whether these medications were given in a timely manner or withheld in the setting of postoperative nausea and vomiting. We modified this protocol and performed a retrospective analysis to assess the impact of this change on postoperative opioid rescue requirements in women undergoing cesarean delivery under neuraxial anesthesia.This retrospective analysis included patients who underwent cesarean deliveries from 1 July 2014 to 22 August 2017. With the initial analgesic protocol, patients received neuraxial morphine, followed by naproxen 500 mg PO Q12 hours and acetaminophen 650-975 mg PO Q6 hours initiated in the recovery room. After protocol revision in January 2016, the same neuraxial morphine dose was used in addition to acetaminophen 975 mg PR at the start of the case and ketorolac 15-30 mg IV at the end of the case. Postoperatively, patients received acetaminophen PO 975 mg Q6 hours, ketorolac IV 15 mg Q6 hours for 3 doses, transitioning to ibuprofen 600 mg Q6 hours. Fentanyl, oxycodone, and intravenous hydromorphone were given for breakthrough pain with both protocols. The primary outcome of the study is the need for rescue opioid analgesia. Secondary outcomes are total opioid usage, time to first rescue opioid, maximum reported pain scores, and need for rescue antiemetics. Univariate and multivariate analyses were performed controlling for variables significantly different between the two cohorts.3250 patients were included in our analysis (1574 in the old protocol and 1676 in the new protocol). There was no significant difference in patient demographics or intraoperative characteristics between the two cohorts except for more primiparous women (25% vs. 17%), more Pfannenstiel incision (98% vs. 96%), and less repeat cesarean deliveries (40% vs. 44%) in the new protocol cohort. Need for rescue opioids was reduced with the new protocol at 2, 24, and 48 h [(36.46% vs. 75.73%,There was a significant decrease in the need for and the dose of rescue opioid medications with the new protocol. This highlights the importance of optimizing the choice of agents, as well as route and timing of administration of the components of the postoperative multimodal analgesic regimen.

Patients who suffer an unintentional dural puncture have a high risk of developing a post-dural puncture headache. Other neurologic complications have been reported, but seizure is rarely seen. We present a case of a 21-year-old primigravida who experienced an unrecognized unintentional dural puncture that ultimately resulted in a tonic-clonic seizure from intracranial hypotension one week following the dural breach. Her trachea was intubated and she was transferred to the intensive care unit. Two epidural blood patches, performed by neuroradiologists, were needed before the patient experienced complete resolution of her headache. During the re-admission, she also experienced a pulmonary embolus which further lengthened her hospital stay.

Background Postoperative nausea and/or vomiting affects up to 80% of parturients undergoing cesarean delivery, but there is a lack of obstetric-specific risk-prediction models. We performed this study to identify postoperative nausea/vomiting risk factors in parturients undergoing cesarean delivery, formulate an obstetric-specific prediction model (Duke score), and compare its performance against the Apfel score. Methods A post-hoc analysis of data from two randomized controlled trials studying nausea/vomiting in women undergoing cesarean delivery with intrathecal morphine. Potential risk factors for postoperative nausea/vomiting within 24 h of surgery with univariate associations with P ≤0.20 were considered for inclusion in the multivariable analysis. After identifying the final multivariable model, we derived our Duke score by assigning points to the selected factors. We then tested the association of the Duke and Apfel scores with postoperative nausea and vomiting, and compared the area-under-the-receiver operating characteristic curve. Results Analysis included 260 parturients, of whom 146 (56.2%) experienced postoperative nausea/vomiting. Non-smoking during pregnancy (OR 2.29 [95% CI 1.12 to 4.67], P=0.023), and history of postoperative nausea/vomiting after cesarean delivery and/or morning sickness (2.09 [1.12 to 3.91], P=0.021) were independent predictors of postoperative nausea/vomiting and included in the Duke score. Both Duke and Apfel scores trended linearly with postoperative nausea/vomiting risk (Duke P=0.001; Apfel P=0.049) and had comparable areas-under-the-receiver operating characteristic curve (Duke 0.63 [0.57 to 0.70]; Apfel 0.59 [0.52 to 0.65], P=0.155). Conclusions Both Duke and Apfel scores exhibited similar but poor predictive performance. Until better tools are developed, routine prophylactic anti-emetics appears to be a reasonable approach in this patient population.

Background Although cesarean delivery is one of the most commonly performed surgical procedures, robust data regarding post-cesarean pain is still lacking. Recent studies showed an association between pain upon local anesthetic (LA) injection for spinal anesthesia, or the use of a "three simple questions", and acute post-cesarean pain. Nevertheless, these assessments have yet to be validated further, despite their relative ease of use. We aimed to assess the association between pain score upon LA injection with acute post-cesarean pain after 24 hours at rest (primary outcome) and sub-acute post-cesarean pain lasting for 4 weeks or more (secondary outcome). Methods Women undergoing cesarean delivery under spinal anesthesia were given pre-operative questionnaires on pain and psychological vulnerability. We also assessed the pain score upon LA injection and mechanical temporal summation. Univariate and multivariable logistic regressions were performed. Results The incidence of moderate-to-severe acute post-cesarean pain at 24 hours was 21.0% (95% CI=16.6-27.6%) (48 of 217 patients). Pain score upon LA injection was not significantly associated with acute post-cesarean pain after 24 hours at rest (unadjusted OR=1.10, 95% CI=0.95-1.27, P=0.21). However, pain score upon LA injection was significantly associated with sub-acute post-cesarean pain (adjusted OR=1.29, 95% CI=1.07-1.55, P=0.0089) with significant covariate of increased pre-operative central sensitization inventory (CSI) scores (adjusted OR=1.05, 95% CI=1.01-1.09, P=0.0111; area under the curve (AUC)=0.691). Conclusion There was no association between increased pain score upon LA injection and acute post-cesarean pain, but it was associated with sub-acute post-cesarean pain. Further work is needed to define pain score upon LA injection as a convenient pragmatic measure of risk stratifying patients predisposed to sub-acute post-cesarean pain.

Background In women undergoing cesarean delivery under spinal anesthesia with intrathecal morphine, transversus abdominis plane (TAP) block with bupivacaine hydrochloride (HCl) may not improve postsurgical analgesia. This lack of benefit could be related to the short duration of action of bupivacaine HCl. A retrospective study reported that TAP block with long-acting liposomal bupivacaine (LB) reduced opioid consumption and improved analgesia following cesarean delivery. Therefore, we performed a prospective multicenter, randomized, double-blind trial examining efficacy and safety of TAP block with LB plus bupivacaine HCl versus bupivacaine HCl alone. Methods Women (n = 186) with term pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomized (1:1) to TAP block with LB 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone. Efficacy was evaluated in a protocol-compliant analysis (PCA) set that was defined a priori. The primary end point was total postsurgical opioid consumption (oral morphine equivalent dosing [MED]) through 72 hours. Pain intensity was measured using a visual analog scale. Adverse events (AEs) after treatment were recorded through day 14. Results Total opioid consumption through 72 hours was reduced with LB plus bupivacaine HCl versus bupivacaine HCl alone (least squares mean [LSM] [standard error (SE)] MED, 15.5 mg [6.67 mg] vs 32.0 mg [6.25 mg]). This corresponded to an LSM treatment difference of -16.5 mg (95% confidence interval [CI], -30.8 to -2.2 mg; P = .012). The area under the curve of imputed pain intensity scores through 72 hours supported noninferiority of LB plus bupivacaine HCl versus bupivacaine HCl alone (LSM [SE], 147.9 [21.13] vs 178.5 [19.78]; LSM treatment difference, -30.6; 95% CI, -75.9 to 14.7), with a prespecified noninferiority margin of 36 (P = .002). In an analysis of all treated patients, including those not meeting criteria for inclusion in the PCA, there was no difference in postsurgical opioid consumption between groups. In the LB plus bupivacaine HCl group, 63.6% of patients experienced an AE after treatment versus 56.2% in the bupivacaine HCl-alone group. Serious AEs after treatment were rare (≈3% in both groups). Conclusions TAP block using LB plus bupivacaine HCl as part of a multimodal analgesia protocol incorporating intrathecal morphine resulted in reduced opioid consumption after cesarean delivery in the PCA set. Results suggest that with correct TAP block placement and adherence to a multimodal postsurgical analgesic regimen, there is an opioid-reducing benefit of adding LB to bupivacaine TAP blocks after cesarean delivery (ClinicalTrials.gov identifier: NCT03176459).

This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.

Objective: To evaluate opioid consumption among parturients with varying degrees of perineal lacerations.Methods: This was a retrospective analysis of women who delivered vaginally at our instituti...

OBJECTIVE: Lumbar punctures (LPs) are important for obtaining CSF in neurology studies but are associated with adverse events and feared by many patients. We determined adverse event rates and pain scores in patients prospectively enrolled in two cohort studies who underwent LPs using a standardized protocol and 25g needle. METHODS: 809 LPs performed in 262 patients age ≥60 years in the MADCO-PC and INTUIT studies were analyzed. Medical records were monitored for LP-related adverse events, and patients were queried about subjective complaints. We analyzed adverse event rates, including headaches and pain scores. RESULTS: There were 22 adverse events among 809 LPs performed, a rate of 2.72% (95% CI 1.71% – 4.09%). Patient hospital stay did not increase due to adverse events. Four patients (0.49%) developed a post-lumbar puncture headache (PLPH). Twelve patients (1.48%) developed nausea, vasovagal responses, or headaches that did not meet PLPH criteria. Six patients (0.74%) reported lower back pain at the LP site not associated with muscular weakness or paresthesia. The median pain score was 1 [0, 3]; the mode was 0 out of 10. CONCLUSIONS: The LP protocol described herein may reduce adverse event rates and improve patient comfort in future studies.

Objective To evaluate the efficacy of wound infusion with ropivacaine plus ketorolac compared with placebo for post-cesarean delivery analgesia in women who received a multimodal analgesic regimen including intrathecal morphine. Methods In a randomized double-blind study, women undergoing scheduled cesarean delivery under spinal or combined spinal epidural anesthesia were randomized to wound infusion with ropivacaine 0.2% plus ketorolac, or saline placebo using an elastometric pump for 48 hours. The primary outcome was pain score with movement at 24 hours after surgery (0-10 scale, 0=no pain and 10=worst possible pain). Secondary outcomes included pain scores at rest at 24 hours, pain scores at rest and with movement at 2 and 48 hours, opioid consumption, and time to first rescue analgesic. A sample size of 35 per group (n=70) was planned. Results From November 8, 2016, to May 17, 2019, 247 women were screened, and 71 completed the study per protocol: 38 in the placebo group and 33 in the ropivacaine plus ketorolac group. Patient demographics and intraoperative characteristics were comparable between the groups. There was no significant difference between the groups in the primary outcome of pain score with movement at 24 hours (difference in median score 0, 95% CI -1 to 2, P=.94). There were also no significant differences between the placebo and ropivacaine plus ketorolac groups in pain scores at other time points, in total opioid consumption (difference in median consumption -12.5 mg, 95% CI -30 to 5, P=.11), or in time to rescue analgesics (median [interquartile range] 660 [9-1,496] vs 954 [244-1,710] minutes, hazard ratio 0.69, 95% CI 0.41 to 1.17, P=.16). Conclusion There was no benefit of wound infusion with ropivacaine and ketorolac in women who received intrathecal morphine and a multimodal analgesic regimen. Clinical trial registration ClinicalTrials.gov, NCT02829944. Funding source The study was supported in part by Avanos Medical Inc.

Chloroprocaine is a short-acting local anesthetic that has been used for spinal anesthesia in outpatient surgery. There is limited experience with spinal chloroprocaine for prophylactic cervical cerclage placement. We sought to determine the effective dose of intrathecal chloroprocaine for 90% of patients (ED90) undergoing prophylactic cervical cerclage placement. We hypothesized that the ED90 of intrathecal chloroprocaine when combined with 10-ug fentanyl would be between 33 and 54 mg.In this prospective 2-center double-blinded study, we enrolled women undergoing prophylactic cervical cerclage placement under combined spinal-epidural anesthesia. A predetermined dose of intrathecal 3% chloroprocaine with fentanyl 10 ug was administered. The initial dose was 45-mg intrathecal chloroprocaine. Subsequent dose adjustments were determined based on the response of the previous subject using an up-down sequential allocation with a biased-coin design. A dose was considered effective if at least a T12 block was achieved, and there was no requirement for epidural activation or intraoperative analgesic supplementation during the procedure. The primary outcome was the ED90 of intrathecal chloroprocaine with fentanyl 10 ug. Secondary outcomes included duration of surgery, anesthetic side effects, time to resolution of motor and sensory block, time to achieve recovery room discharge criteria, and patient satisfaction with anesthetic care. Isotonic regression was used to estimate the ED90.Forty-seven patients were enrolled into the study. Two patients were excluded (1 protocol violation and 1 failed block). In total, 45 patients completed the study. The estimated ED90 (95% confidence interval) for intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg (45.0-50.1 mg). The median (interquartile range [IQR]) duration of surgery was 15 (10-24) minutes. Resolution of the motor (Bromage 0) and sensory block took a median time of 60 (45-90) minutes and 90 (75-105) minutes, respectively. The median time to achieve recovery room discharge criteria was 150 (139-186) minutes. Satisfaction with anesthetic management was high in all patients. There were no reports of postdural puncture headache or transient neurological symptoms postoperatively.The ED90 of intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg. Intrathecal chloroprocaine was associated with rapid block recovery and high patient satisfaction, which makes it well suited for outpatient obstetric procedures.

Determine if intravenous iron for antenatal anemia is associated with reduced incidence of postnatal depression (PND) within 12 months.This retrospective cohort study included adult women with antenatal anemia (hemoglobin value of 11.0 g/dL within 3 months before delivery). PND was defined as Edinburgh Postnatal Depression Scale (EPDS) or Patient Health Questionnaire-9 (PHQ-9) ≥ 10. Data on intravenous iron, lowest hemoglobin concentration, EPDS and PHQ-9 scores, insurance status, history of anxiety, depression, chronic pain, and substance use, obstetric complications, labor analgesia, and mode of delivery were obtained. Standardized mean difference (SMD) was estimated and multivariable logistic regression models were constructed with adjustment for potential confounders with absolute SMD of ≥ 0.1.Data from 3988 women were analyzed. The 368 (9.2%) women who received intravenous iron therapy had lower antenatal hemoglobin levels, were more likely to be African American or single/widowed women, and more commonly had Medicaid coverage, repeat cesarean delivery, and history of depression compared to those who did not receive intravenous iron therapy. Unadjusted analysis showed women who received intravenous iron had higher incidence of PND (18.5%) than those who did not (13.4%) (p = 0.008). Multivariable analysis showed no significant association between intravenous iron and PND incidence (aOR 1.21, 95%CI 0.89-1.63, p = 0.232), although history of depression (aOR 2.42, 95%CI 1.91-3.08, p 0.001), higher gravidity (aOR 1.09, 95%CI 1.02-1.17, p = 0.016), and Medicaid insurance (aOR 1.44, 95%CI 1.16-1.80, p = 0.001) were independently associated with PND.Intravenous iron for antenatal anemia was not associated with significant change in the incidence of PND.

Opioids for managing postoperative pain are associated with side effects including opioid-induced respiratory depression (OIRD) and gastrointestinal complications. Opioids induce analgesia via G-protein signaling, while adverse effects are mediated by the β-arrestin pathway. Oliceridine is a biased ligand that preferentially activates G-protein signaling over β-arrestin, theoretically reducing adverse effects. Oliceridine has been approved by the Food and Drug Administration to treat acute pain severe enough to require intravenous opioid analgesics.Preclinical and clinical trials demonstrate the analgesic efficacy of oliceridine. Available evidence suggests that oliceridine may have a lower risk of OIRD and gastrointestinal complications compared to conventional opioids.The analgesic efficacy of oliceridine has been evaluated in several clinical trials. However, safety data were obtained from an open-label observational study and studies assessing adverse effects as secondary outcomes, as post-hoc analyses, or from retrospective studies. These may be affected by gaps in detecting adverse events, heterogeneity in the original studies, and the limitations of retrospective studies. Prospective trials examining the safety of oliceridine versus conventional opioids are needed. Studies are also needed to assess the safety and efficacy of oliceridine in obstetric and pediatric populations, and in the context of multimodal analgesia and Enhanced Recovery after Surgery protocols.

BackgroundEarly 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.MethodsDeliveries 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

We conducted an updated systematic review and meta-analysis on maternal outcomes associated with uterine exteriorization compared with in situ repair in women undergoing Cesarean delivery.We searched for randomized controlled trials comparing uterine exteriorization with in situ repair during Cesarean delivery. Primary outcomes were intraoperative nausea and vomiting (IONV) and perioperative decrease in hemoglobin concentration. Secondary outcomes were postoperative nausea and vomiting (PONV), estimated blood loss, fever, endometritis, wound infection, intraoperative and postoperative pain, postoperative analgesic use, duration of surgery and hospital stay, and time to return of bowel function.Twenty studies with 20,909 parturients were included. Exteriorization was associated with higher risk of IONV (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.66 to 2.63; IIn this updated systematic review and meta-analysis, uterine exteriorization was associated with an increased risk of IONV but no significant change in perioperative hemoglobin decrease compared with in situ repair.PROSPERO (CRD42020190074); registered 5 July 2020.RéSUMé: OBJECTIF: Nous avons réalisé une mise à jour d’une revue systématique et une méta-analyse portant sur les issues maternelles associées à l’extériorisation de l’utérus par rapport à une réparation in situ chez les femmes accouchant par césarienne. MéTHODE: Nous avons recherché des études randomisées contrôlées comparant l’extériorisation de l’utérus à la réparation in situ pendant un accouchement par césarienne. Les critères d’évaluation principaux étaient les nausées et vomissements peropératoires (NVPerO) et la réduction périopératoire de l’hémoglobine. Les critères d’évaluation secondaires étaient les nausées et vomissements postopératoires (NVPO), la perte de sang estimée, la fièvre, l’endométrite, l’infection de la plaie, la douleur per- et postopératoire, l’utilisation d’analgésiques postopératoires, la durée de la chirurgie et du séjour à l’hôpital, et le délai jusqu’au retour du transit. RéSULTATS: Vingt études portant sur 20 909 parturientes ont été incluses. L’extériorisation était associée à un risque plus élevé de NVPerO (rapport de cotes [RC], 2,09; intervalle de confiance à 95 % [IC], 1,66 à 2,63; I

IntroductionAdvanced age and obesity are reported to increase the risk of opioid-induced respiratory depression (OIRD). Oliceridine, an intravenous opioid, is a G-protein-biased agonist at the µ-opioid receptor that may provide improved safety. The recent phase 3 ATHENA open-label, multicenter study evaluated postoperative use of oliceridine in patients with moderate-to-severe acute pain. This exploratory analysis of the ATHENA data examined the incidence of OIRD in older (≥ 65years) and/or obese (BMI ≥ 30kg/m2) patients and analyzed risk factors of OIRD.MethodsPatients aged ≥ 18years with a score ≥ 4 on an 11-point numeric pain rating scale (NPRS) received IV oliceridine as needed via bolus dosing and/or patient-controlled analgesia (PCA). OIRD occurring within 48h of last dose of oliceridine was defined using two established definitions: (1) naloxone use, (2) respiratory rate

Current pain and analgesic management strategies apply a standardized one-size-fits-all approach to women undergoing cesarean delivery. These standardized protocols do not account for significant variability in women's pain and may lead to under-treatment in patients with high analgesic needs and overtreatment, associated with increased analgesic-related side effects, in women with low analgesic needs and higher analgesic drug sensitivity. Pre-operative identification of patients at-risk of developing severe pain might allow clinicians to optimize care by offering personalized, stratified or targeted analgesic treatment protocols. Pre-operative pain prediction tools are only of moderate value in this regard. Pain reporting during local anesthetic infiltration and answering simple rating questions about anticipated pain and analgesic needs are the easiest tools to apply and show some promise for post-cesarean delivery pain prediction. Patient-driven analgesic dose and protocol selection (based on individual preferences for pain relief and for avoidance of side effects after cesarean delivery) may optimally balance individual pain needs and side effect concerns compared to standardized postoperative pain treatment protocols. Individualized or stratified post-discharge opioid prescribing practices have been shown to reduce unnecessary opioid analgesic prescriptions and consumption, so should be implemented routinely. Outcomes other than pain and analgesic use, including recovery measures and maternal satisfaction metrics, should be considered when evaluating personalized or patient-selected pain treatment protocols.

Obesity is a significant global health problem. It results in a higher incidence of complications for pregnant women and their neonates. Cesarean deliveries are more common in obese parturients as well. The increased burden of comorbidities seen in this population, such as obstructive sleep apnea, necessitates antepartum anesthetic consultation. These patients pose unique challenges for the practicing anesthesiologist and may benefit from optimization prior to delivery. Complications from anesthesia and overall morbidity and mortality are higher in this population. Neuraxial anesthesia can be challenging to place in the obese parturient, but is the preferred anesthetic for cesarean delivery to avoid airway manipulation, minimize aspiration risk, prevent fetal exposure to volatile anesthetic, and decrease risk of post-partum hemorrhage from volatile anesthetic exposure. Monitoring and positioning of these patients for surgery may pose specific challenges. Functional labor epidural catheters can be topped up to provide conditions suitable for surgery. In the absence of a working epidural catheter, a combined spinal epidural anesthetic is often the technique of choice due to relative ease of placement versus a single shot spinal technique as well as the ability to extend the anesthetic through the epidural portion. For cesarean delivery with a vertical supraumbilical skin incision, a two-catheter technique may be beneficial. Concern for thromboembolism necessitates early mobilization and a multimodal analgesic regimen can help accomplish this. In addition, thromboprophylaxis is recommended in this population after delivery-especially cesarean delivery. These patients also need close monitoring in the post-partum period when they are at increased risk for several complications.

Sergio D Bergese,1 Marek Brzezinski,2 Gregory B Hammer,3 Timothy L Beard,4 Peter H Pan,5 Sharon E Mace,6 Richard D Berkowitz,7 Kristina Cochrane,8 Linda Wase,8 Harold S Minkowitz,9 Ashraf S Habib10 1School of Medicine, Stony Brook University, Stony Brook, NY, USA; 2School of Medicine, University of California San Francisco, VA Medical Center, San Francisco, CA, USA; 3Stanford University School of Medicine, Stanford, CA, USA; 4Clinical Research, Summit Medical Group/Bend Memorial Clinic, Bend, OR, USA; 5Wake Forest School of Medicine, Winston-Salem, NC, USA; 6Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA; 7Phoenix Clinical Research, Tamarac, FL, USA; 8Trevena, Inc., Chesterbrook, PA, USA; 9HD Research Corporation, Houston, TX, USA; 10Duke University Medical Center, Durham, NC, USACorrespondence: Sergio D BergeseSchool of Medicine, Stony Brook University, Health Sciences Center, Level 4, Room 060, Stony Brook, NY 11794, USATel +1 631-444-2979Fax +1-631-444-2907Email Sergio.Bergese@stonybrookmedicine.eduBackground: Pain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of β-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the μ-opioid receptor with less recruitment of β-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions.Methods: Adult patients with a score ≥4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures.Results: A total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% ≥65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 ± 2.3 at 30 mins from a score of 6.3 ± 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients.Conclusion: Oliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied.ClinicalTrials.gov identifier: NCT02656875.Keywords: acute pain, analgesia, patient-controlled, clinical trial &nbsp

Gabapentinoid use has increased substantially in the past several years after initial promising data with regard to acute perioperative pain control. The purpose of this review is to critically appraise the evidence for the use of gabapentinoids for acute pain management and its impact on the development of chronic pain after surgery.Recent meta-analyses have revealed that prior data likely have overestimated the beneficial effects of gabapentinoids in acute perioperative pain while underestimating the associated adverse effects. The utility of gabapentinoids in the setting of enhanced recovery pathways and for the prevention of chronic postsurgical pain is still unclear. Moreover, there has been increasing concern regarding the potential for misuse and abuse of gabapentinoids.Current evidence does not support the routine use of gabapentinoids as part of a multimodal analgesic regimen in enhanced recovery pathways. We recommend being selective with regard to using gabapentinoids for acute postoperative pain management after careful consideration of the potential side effect profile based on patient comorbidities as well as the expected severity of postoperative pain. Large, high-quality trials are needed to identify the impact of gabapentinoids in the context of multimodal anagelsia.

We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri-operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51-0.75) (I2 =57%, p&nbsp