The 90% effective dose of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal-epidural anesthesia in parturients with super obesity: an up-down sequential allocation study.

PURPOSE: To determine the 90% effective dose (ED90) of intrathecal hyperbaric bupivacaine for Cesarean delivery under combined spinal-epidural anesthesia (CSE) in parturients with super obesity (body mass index [BMI] ≥ 50 kg·m-2). METHODS: We enrolled parturients with BMI ≥ 50 kg·m-2 with term, singleton vertex pregnancies undergoing elective Cesarean delivery under CSE. An independent statistician generated the 0.75% hyperbaric bupivacaine dosing regimen in increments of 0.75 mg using a biased-coin up-down sequential allocation technique. This was combined with 15 µg fentanyl, 150 µg morphine, and normal saline to a volume of 2.05 mL. The initial and maximum doses were 9.75 mg and 12 mg, respectively. Participants, clinical team, and outcome assessors were blinded to the dose. The primary outcome was block success, defined as T6 block to pinprick within ten minutes and no intraoperative analgesic supplementation within 90 min of spinal injection. We determined the ED90 using logistic regression. RESULTS: We enrolled 45 parturients and included 42 in the analysis. All doses achieved a T6 level within ten minutes, and the primary outcome occurred in 0/1 (0%) of the 9.75-mg doses, 2/3 (67%) of the 10.5-mg doses, 21/27 (78%) of the 11.25-mg doses, and 11/11 (100%) of the 12-mg doses. The ED90 of hyperbaric bupivacaine was 11.56 mg (95% confidence interval, 11.16 to 11.99). Four parturients (9.5%) had sensory level higher than T2, but none was symptomatic or required general anesthesia. CONCLUSION: The estimated ED90 of hyperbaric bupivacaine with fentanyl and morphine in parturients with super obesity undergoing Cesarean delivery under CSE was approximately 11.5 mg. STUDY REGISTRATION: ClinicalTrials.gov (NCT03781388); first submitted 18 December 2018.

RéSUMé: OBJECTIF: Notre objectif était de déterminer la dose efficace à 90 % (DE90) de bupivacaïne hyperbare intrathécale pour l'accouchement par césarienne sous péri-rachianesthésie combinée (PRC) chez les personnes parturientes atteintes de super obésité (indice de masse corporelle [IMC] ≥ 50 kg·m−2). MéTHODE: Nous avons recruté des personnes parturientes ayant un IMC ≥ 50 kg·m−2 présentant des grossesses uniques à terme, en présentation céphalique et bénéficiant d'un accouchement par césarienne programmée sous PRC. Un·e statisticien·ne indépendant·e a généré le schéma posologique de bupivacaïne hyperbare à 0,75 % par incréments de 0,75 mg à l'aide d'une technique d'allocation séquentielle en escalier. La bupivacaïne a été combinée à 15 µg de fentanyl, 150 µg de morphine et à une solution physiologique salée jusqu'à un volume de 2,05 mL. Les doses initiale et maximale étaient respectivement de 9,75 mg et 12 mg. Les participant·es, l'équipe clinique et les personnes évaluant les résultats n'avaient pas connaissance de la dose. Le critère d'évaluation principal était la réussite du bloc, définie comme un bloc à T6 à la piqûre dans les dix minutes et aucune supplémentation analgésique peropératoire dans les 90 minutes suivant l'injection rachidienne. Nous avons déterminé la DE90 à l'aide d'une méthode de régression logistique. RéSULTATS: Nous avons recruté 45 personnes parturientes et en avons inclus 42 dans l'analyse. Toutes les doses ont atteint le niveau T6 en dix minutes, et le critère d'évaluation principal a été obtenu pour 0/1 (0 %) des doses de 9,75 mg, 2/3 (67 %) des doses de 10,5 mg, 21/27 (78 %) des doses de 11,25 mg et 11/11 (100 %) des doses de 12 mg. La DE90 de bupivacaïne hyperbare était de 11,56 mg (intervalle de confiance à 95 %, 11,16 à 11,99). Quatre personnes parturientes (9,5 %) ont affiché un niveau sensoriel supérieur à T2, mais aucune n'était symptomatique ni n'a nécessité d'anesthésie générale. CONCLUSION: La DE90 estimée de bupivacaïne hyperbare avec fentanyl et morphine chez les personnes parturientes hyperobèses bénéficiant d'une césarienne sous PRC était d'environ 11,5 mg. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT03781388); soumis pour la première fois le 18 décembre 2018.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

The Association of Guideline-Directed Prophylaxis With Postoperative Nausea and Vomiting in Adult Patients: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Consensus guidelines for postoperative nausea and vomiting (PONV) prophylaxis recommend a risk-based approach in which the number of antiemetics administered is based on a preoperative estimate of PONV risk. These guidelines have been adapted by the Multicenter Perioperative Outcomes Group (MPOG) to serve as measures of clinician and hospital compliance with guideline-recommended care. However, the impact of this approach on clinical outcomes is not known. METHODS: We performed a single-center, retrospective study of adult patients undergoing general anesthesia from 2018 to 2021. Risk factors for PONV were defined using MPOG definitions: female sex, history of PONV or motion sickness, nonsmoker, inhaled anesthesia >60 minutes, high-risk procedure (cholecystectomy, laparoscopic, gynecologic), and age <50 years. Adequate prophylaxis was defined using the MPOG PONV-05 metric: at least 2 agents for patients with 1 to 2 risk factors and at least 3 agents for patients with 3+ risk factors. PONV was defined as documented PONV or receipt of rescue antiemetics. To estimate the association between adequate prophylaxis and PONV, we used Bayesian binomial models with overlap propensity score weighting. RESULTS: We included 76,703 cases (43% receiving adequate prophylaxis) with PONV occurring in 19%. In unadjusted and unweighted comparison, adequate prophylaxis was associated with increased incidence of PONV: median odds ratio 1.21 (95% credible interval [1.16-1.25]). However, after propensity score weighting and multivariable adjustment, adequate prophylaxis was associated with reduced relative and absolute risk for PONV: weighted marginal median odds ratio 0.90 [0.84-0.98] and absolute risk reduction (ARR) 1.6% [0.6%-2.6%]. There was evidence for a differential effect of adequate prophylaxis across the guideline-defined risk spectrum, with benefit seen in patients with 1 to 5 risk factors (conditional probabilities of benefit >0.81), but not in those at high predicted risk. Patient-specific, covariate-adjusted ARR was heterogeneous, with a median patient-specific conditional probability of benefit of 0.84 (95% credible interval, 0.73-0.90). CONCLUSIONS: Guideline-directed PONV prophylaxis is associated with a modest reduction in PONV, although this effect is small and heterogeneous on the absolute scale. We found evidence for a differential association between adequate prophylaxis and PONV across the guideline-defined risk spectrum, with diminution in patients at very high predicted preoperative risk. While patient-specific benefit was heterogenous, most patients had reasonably high predicted probabilities of absolute benefit from a guideline-directed strategy. Further assessment of these associations in a multicenter setting, with more robust investigation of risk prediction methods will allow for better understanding of the optimal approach to PONV prophylaxis.

Maternal Morbidity According to Mode of Delivery Among Pregnant Patients With Pulmonary Hypertension.

BACKGROUND: Patients with pulmonary hypertension have a high risk of maternal morbidity and mortality. It is unknown if a trial of labor carries a lower risk of morbidity in these patients compared to a planned cesarean delivery. The objective of this study was to examine the association of delivery mode with severe maternal morbidity events during delivery hospitalization among patients with pulmonary hypertension. METHODS: This retrospective cohort study used the Premier inpatient administrative database. Patients delivering ≥25 weeks gestation from January 1, 2016, to September 30, 2020, and with pulmonary hypertension were included. The primary analysis compared intended vaginal delivery (ie, trial of labor) to intended cesarean delivery (intention to treat analysis). A sensitivity analysis was conducted comparing vaginal delivery to cesarean delivery (as treated analysis). The primary outcome was nontransfusion severe maternal morbidity during the delivery hospitalization. Secondary outcomes included blood transfusion (4 or more units) and readmission to the delivery hospital within 90 days from discharge from delivery hospitalization. RESULTS: The cohort consisted of 727 deliveries. In the primary analysis, there was no difference in nontransfusion morbidity between intended vaginal delivery and intended cesarean delivery groups (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], 0.49-1.15). In secondary analyses, intended cesarean delivery was not associated with blood transfusion (aOR, 0.71; 95% CI, 0.34-1.50) or readmission within 90 days (aOR, 0.60; 95% CI, 0.32-1.14). In the sensitivity analysis, cesarean delivery was associated with a 3-fold higher risk of nontransfusion morbidity compared to vaginal delivery (aOR, 2.64; 95% CI, 1.54-3.93), a 3-fold higher risk of blood transfusion (aOR, 3.06; 95% CI, 1.17-7.99), and a 2-fold higher risk of readmission within 90 days (aOR, 2.20; 95% CI, 1.09-4.46) compared to vaginal delivery. CONCLUSIONS: Among pregnant patients with pulmonary hypertension, a trial of labor was not associated with a higher risk of morbidity compared to an intended cesarean delivery. One-third of patients who required an intrapartum cesarean delivery had a morbidity event, demonstrating the increased risk of adverse events in this group.

Placenta accreta spectrum care infrastructure: an evidence-based review of needed resources supporting placenta accreta spectrum care.

The incidence of placenta accreta spectrum, the deeply adherent placenta with associated increased risk of maternal morbidity and mortality, has seen a significant rise in recent years. Therefore, there has been a rise in clinical and research focus on this complex diagnosis. There is international consensus that a multidisciplinary coordinated approach optimizes outcomes. The composition of the team will vary from center to center; however, central themes of complex surgical experts, specialists in prenatal diagnosis, critical care specialists, neonatology specialists, obstetrics anesthesiology specialists, blood bank specialists, and dedicated mental health experts are universal throughout. Regionalization of care is a growing trend for complex medical needs, but the location of care alone is just a starting point. The goal of this article is to provide an evidence-based framework for the crucial infrastructure needed to address the unique antepartum, delivery, and postpartum needs of the patient with placenta accreta spectrum. Rather than a clinical checklist, we describe the personnel, clinical unit characteristics, and breadth of contributing clinical roles that make up a team. Screening protocols, diagnostic imaging, surgical and potential need for critical care, and trauma-informed interaction are the basis for comprehensive care. The vision from the author group is that this publication provides a semblance of infrastructure standardization as a means to ensure proper preparation and readiness.

Comparison of the Efficacy of HSK3486 and Propofol for Induction of General Anesthesia in Adults: A Multicenter, Randomized, Double-blind, Controlled, Phase 3 Noninferiority Trial.

BACKGROUND: Propofol is an intravenous anesthetic associated with hypotension, respiratory depression, and injection-site pain. HSK3486 injectable emulsion (ciprofol) is a 2,6-disubstituted phenol derivative with fast onset and quick, stable recovery. Previous studies support HSK3486 as an effective, safe anesthetic with substantially less injection-site pain than propofol. The primary objective of this study was to investigate the noninferiority of HSK3486 compared with propofol in successful general anesthesia induction. METHODS: Two hundred fifty-five participants were enrolled in HSK3486-304, a multicenter, randomized (2:1), double-blind, propofol-controlled, phase 3 study evaluating HSK3486 for general anesthesia induction in adults undergoing elective surgery with tracheal intubation. The primary endpoint was successful anesthesia induction, defined as 1 or less on the Modified Observer's Assessment of Alertness/Sedation scale. Key secondary endpoints were proportion of participants with injection-site pain on the Numerical Rating Scale of 1 or greater and a composite endpoint, including the proportion of participants successfully induced while maintaining the desired anesthetic depth and without substantial cardiac and respiratory events. Safety endpoints included adverse events, abnormal vital signs, and injection-site pain. RESULTS: Two hundred fifty-one participants (HSK3486, n = 168; propofol, n = 83) were included in the analyses. General anesthesia was successfully induced in 97.0% versus 97.6% of participants with HSK3486 and propofol, respectively. The difference in success rate was -0.57% (95% CI, -5.4 to 4.2%); the noninferiority boundary of -8% was not crossed. Thirty participants (18.0%) had injection-site pain with HSK3486 versus 64 (77.1%) with propofol (P < 0.0001). Eighty-one participants (48.2%) with HSK3486 versus 42 (50.6%) with propofol (P = 0.8780) satisfied the composite endpoint. When injection-site pain was excluded, the incidence of treatment-emergent adverse events related to study drug was 17.9% for HSK3486 and 14.5% for propofol. CONCLUSIONS: The study met its primary objective and endpoint, demonstrating noninferiority of HSK3486 compared with propofol in successful anesthetic induction. Substantially less injection-site pain was associated with HSK3486 than with propofol.

Severe Maternal Morbidity According to Mode of Delivery Among Pregnant Patients With Cardiomyopathies.

BACKGROUND: Women with cardiomyopathies are at risk for pregnancy complications. The optimal mode of delivery in these patients is guided by expert opinion and limited small studies. OBJECTIVES: The objective of this study is to examine the association of delivery mode with severe maternal morbidity events during delivery hospitalization and readmissions among patients with cardiomyopathies. METHODS: The Premier inpatient administrative database was used to conduct a retrospective cohort study of pregnant patients with a diagnosis of a cardiomyopathy. Utilizing a target trial emulation strategy, the primary analysis compared outcomes among patients exposed to intended vaginal delivery vs intended cesarean delivery (intention to treat). A secondary analysis compared outcomes among patients who delivered vaginally vs by cesarean (as-treated). Outcomes examined were nontransfusion severe maternal morbidity during the delivery hospitalization, blood transfusion, and readmission. RESULTS: The cohort consisted of 2,921 deliveries. In the primary analysis (intention to treat), there was no difference in nontransfusion morbidity (adjusted OR [aOR]: 1.17; 95% CI: 0.91-1.51), blood transfusion (aOR: 1.27; 95% CI: 0.81-1.98), or readmission (aOR: 1.03; 95% CI: 0.73-1.44) between intended vaginal delivery and intended cesarean delivery. In the as-treated analysis, cesarean delivery was associated with a 2-fold higher risk of nontransfusion morbidity (aOR: 2.44; 95% CI: 1.85-3.22) and blood transfusion (aOR: 2.26; 95% CI: 1.34-3.81) when compared with vaginal delivery. CONCLUSIONS: In patients with cardiomyopathies, a trial of labor does not confer a higher risk of maternal morbidity, blood transfusion, or readmission compared with planned cesarean delivery.

Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study.

PURPOSE: Severe acute pain after Cesarean delivery increases the risk of developing persistent pain (~20% incidence) and postpartum depression (PPD) (~15% incidence). Both conditions contribute to maternal morbidity and mortality, yet early risk stratification remains challenging. Neuroinflammation has emerged as a key mechanism of persistent pain and depression in nonobstetric populations. Nevertheless, most studies focus on plasma cytokines, and the relationship between plasma and cerebrospinal fluid (CSF) cytokine levels is unclear. Our primary aim was to compare inflammatory marker levels between patients who developed the composite outcome of persistent pain and/or PPD vs those who did not. METHODS: We recruited term patients with singleton pregnancies undergoing elective Cesarean delivery under neuraxial anesthesia into an exploratory prospective cohort study. We collected baseline demographic, obstetric, and Edinburgh Postnatal Depression Scale information, and performed quantitative sensory tests. Plasma was collected preoperatively and 48 hr postoperatively. In the operating room, 10 mL of CSF was collected, followed by a standardized anesthetic. Intra- and postoperative management were according to standard practice. We obtained Edinburgh Postnatal Depression Scale and pain scores at six weeks and three months after delivery. The primary outcome was persistent pain and/or PPD at three months. We analyzed the difference in inflammatory marker levels between the groups (primary aim) using two-sided Mann-Whitney tests. RESULTS: Eighty participants were enrolled, and 63 patients completed the study; 23 (37%) experienced the primary outcome at three months. Preoperative plasma transforming growth factor beta 1 (TGF-ß1) concentration was higher in patients who developed the primary outcome compared with those who did not (median [interquartile range (IQR)], 2,879 [2,241-5,494] vs 2,292 [1,676-2,960] pg·mL-1; P = 0.04), while CSF IL-1ß concentration was higher in patients who developed the primary outcome than in those who did not (median [IQR], 0.36 [0.29-0.39] vs 0.30 [0.25-0.35] pg·mL-1; P = 0.03). CONCLUSIONS: We observed differential levels of plasma and CSF inflammatory biomarkers in patients who developed persistent pain and PPD compared with those who did not. We showed the feasibility of collecting plasma and CSF samples at Cesarean delivery, which may prove useful for future risk-stratification. STUDY REGISTRATION: ClinicalTrials.gov (NCT04271072); registered 17 February 2020.

RéSUMé: OBJECTIF: La douleur aiguë sévère après un accouchement par césarienne augmente le risque de douleur persistante (~20 % d'incidence) et de dépression post-partum (DPP) (~15 % d'incidence). Ces deux conditions contribuent à la morbidité et à la mortalité maternelles, mais la stratification précoce des risques demeure difficile. La neuroinflammation est apparue comme un mécanisme clé de la douleur persistante et de la dépression dans les populations non obstétricales. Néanmoins, la plupart des études se concentrent sur les cytokines plasmatiques, et la relation entre les taux de cytokines plasmatiques et de liquide céphalorachidien (LCR) n'est pas claire. Notre objectif principal était de comparer les taux de marqueurs inflammatoires entre les patient·es qui ont eu un résultat composite de douleur persistante et/ou de DPP vs les personnes qui n'en ont pas eu. MéTHODE: Nous avons recruté des patient·es à terme avec des grossesses uniques bénéficiant d'une césarienne programmée sous anesthésie neuraxiale dans une étude de cohorte prospective exploratoire. Nous avons recueilli des informations démographiques de base, obstétricales et tirées de l'Échelle de dépression postnatale d'Édimbourg, et effectué des tests sensoriels quantitatifs. Le plasma a été prélevé avant l'opération et 48 heures après l'opération. En salle d'opération, 10 mL de LCR ont été recueillis, suivis d'un anesthésie standardisée. La prise en charge per- et postopératoire était conforme à la pratique courante. Nous avons obtenu les scores sur l'Échelle de dépression postnatale d'Édimbourg et les scores de douleur six semaines et trois mois après l'accouchement. Le critère d'évaluation principal était la douleur persistante et/ou la DPP à trois mois. Nous avons analysé la différence dans les niveaux de marqueurs inflammatoires entre les groupes (objectif principal) en utilisant des tests bilatéraux de Mann-Whitney. RéSULTATS: Quatre-vingts personnes ont été recrutées et 63 patient·es ont terminé l'étude; 23 (37 %) ont rapporté le critère d'évaluation principal à trois mois. Le facteur TGF-ß1 (transforming growth factor beta 1) plasmatique préopératoire était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal par rapport aux personnes qui ne l'ont pas manifesté (médiane [écart interquartile (ÉIQ)], 2879 [2241-5494] vs 2292 [1676­2960] pg·mL−1; P = 0,04), tandis que le IL-1ß dans le LCR était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal que chez les personnes qui ne l'ont pas manifesté (médiane [ÉIQ], 0,36 [0,29-0,39] vs 0,30 [0,25­0,35] pg·mL−1; P = 0,03). CONCLUSION: Nous avons observé des taux différentiels de biomarqueurs inflammatoires plasmatiques et de LCR chez les patient·es qui ont manifesté une douleur persistante et une DPP par rapport aux personnes qui n'en ont pas manifesté. Nous avons montré la faisabilité de la collecte d'échantillons de plasma et de LCR lors de l'accouchement par césarienne, ce qui pourrait s'avérer utile pour la stratification future des risques. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT04271072); enregistrée le 17 février 2020.

Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.

BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS: A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS: As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.).

Society of Anesthesia and Sleep Medicine and the Society for Obstetric Anesthesia and Perinatology Consensus Guideline on the Screening, Diagnosis, and Treatment of Obstructive Sleep Apnea in Pregnancy.

The Society of Anesthesia and Sleep Medicine and the Society for Obstetric Anesthesia and Perinatology tasked an expert group to review existing evidence and to generate recommendations on the screening, diagnosis, and treatment of patients with obstructive sleep apnea during pregnancy. These recommendations are based on a systematic review of the available scientific evidence and expert opinion when scientific evidence is lacking. This guideline may not be appropriate for all clinical situations and patients, and physicians must decide whether these recommendations are appropriate for their patients on an individual basis. We recognize that not all pregnant people may identify as women. However, data on non-cisgendered pregnant patients are lacking, and many published studies use gender-binary terms; therefore, depending on the study referenced, we may refer to pregnant individuals as women. This guideline may inform the creation of clinical protocols by individual institutions that consider the unique considerations of their patient populations and the available resources.

Peri-operative anaesthetic management of women with obesity.

Obesity in women is prevalent and growing at an alarming pace worldwide, resulting in significant healthcare and socioeconomic consequences. Obesity is a multisystemic disease that is associated with numerous comorbidities, particularly sleep-disordered breathing, hypertension, coronary artery disease, pulmonary hypertension, thromboembolism, and diabetes mellitus. Additionally, obesity poses several peri-operative challenges including difficulty with airway management and mechanical ventilation, challenges with intravenous access or regional blocks, the need for modified anaesthetic drug dosing, the requirement for correctly sized and rated equipment, and appropriate post-operative monitoring. Therefore, early multidisciplinary planning is crucial to identify and address important peri-operative and clinical issues. Parturients with obesity are especially at high risk due to the additional physiological changes and obstetric comorbidities associated with obesity. Antenatal anaesthetic consultation along with close communication and collaboration within the multidisciplinary team are important to improve maternal and neonatal safety.

Neurokinin-1 receptor antagonists for the prevention of postoperative nausea and vomiting.

Despite the availability of several classes of antiemetics, postoperative nausea and vomiting (PONV) remains a substantial burden for patients following surgery, resulting in patient dissatisfaction and prolonged stays in post-anesthesia care units and ultimately increasing the cost of care. Enhanced recovery protocols and PONV management guidelines are now centered on the assessment of the individual patient's risk for developing PONV, as well as multimodal prophylaxis using antiemetics targeting different mechanisms of action. Over the last two decades, the neurokinin-1 receptor (NK1R) has emerged as a therapeutic target for the management of PONV. This review of the literature explains the role of the NK1R and its ligand-substance P-in vomiting, describes the pharmacologic and pharmacokinetic properties of NK1R antagonists (NK1RAs) and summarizes the clinical evidence supporting NK1RAs for PONV prophylaxis in patients undergoing surgery. In particular, we discuss the therapeutic application of NK1RA in PONV prophylaxis protocols owing to their advantages over other antiemetic classes in efficacy, duration of efficacy, safety, pharmacology, and ease of administration. Future studies will be aimed at further investigating the efficacy and safety of NK1RA-based multimodal combinations, particularly among vulnerable populations (e.g., children and elderly).

A pharmacological overview of aprepitant for the prevention of postoperative nausea and vomiting.

INTRODUCTION: Post-operative nausea and vomiting (PONV) affects 30% of all patients undergoing surgery and up to 80% of high-risk patients. Antiemetics for PONV prophylaxis target a variety of receptor systems, with varying degrees of efficacy and side effect profile. Neurokinin -1 receptor antagonists are the most recent class of compounds investigated for PONV prophylaxis, with aprepitant being the only one currently approved for this indication. AREAS COVERED: This review covers the pathophysiology of PONV, current recommendations for PONV prophylaxis, pharmacokinetics, and pharmacodynamics of aprepitant, and the evidence for its efficacy in the management of PONV as a single agent and in combination therapy. EXPERT OPINION: Aprepitant is effective for PONV prophylaxis. It has superior antivomiting efficacy, long half-life, and favorable side effect profile. Data on antiemetic combinations involving aprepitant are limited, and it is not clear if the addition of other antiemetics to aprepitant results in improved PONV prophylaxis. The oral route of administration of aprepitant is a potential limitation in a busy clinical practice. However, the recent approval of an intravenous formulation could provide a more convenient route of administration. Aprepitant remains more expensive than other antiemetics, and there are no studies assessing the cost effectiveness of its use.

The Association of Guideline-Directed Prophylaxis with Postoperative Nausea and Vomiting in Pediatric Patients: A Single-Center, Retrospective Cohort Study.

BACKGROUND: Guidelines for postoperative nausea and vomiting (PONV) prophylaxis in pediatric patients recommend escalation of the number of antiemetics based on a preoperative estimate of PONV risk. These recommendations have been translated into performance metrics, most notably by the Multicenter Perioperative Outcomes Group (MPOG), used at over 25 children's hospitals. The impact of this approach on clinical outcomes is not known. METHODS: We performed a single-center, retrospective study of pediatric general anesthetic cases from 2018 to 2021. PONV risk factors were defined using MPOG definitions: age ≥3 years, volatile use ≥30 minutes, PONV history, long-acting opioids, female ≥12 years, and high-risk procedure. Adequate prophylaxis was defined using the MPOG PONV-04 metric: 1 agent for 1 risk factor, 2 agents for 2 risk factors, and 3 agents for 3+ risk factors. PONV was defined as documented postoperative nausea/emesis or administration of a rescue antiemetic. Given the nonrandomized allocation of adequate prophylaxis, we used Bayesian binomial models with propensity score weighting. RESULTS: A total of 14,747 cases were included, with PONV in 11% (9% adequate prophylaxis versus 12% inadequate). Overall, there was evidence for reduced incidence of PONV with adequate prophylaxis: weighted median odds ratio 0.82 (95% credible interval, 0.66-1.02; probability of benefit, 0.97) and weighted marginal absolute risk reduction 1.3% (-0.1% to 3.1%). In unweighted estimates, there was an interaction between sum of risk factors and the association of adequate prophylaxis with PONV, with reduced incidence in patients with 1 to 2 risk factors (probability of benefit 0.96 and 0.95) but increased incidence in patients with 3+ risk factors receiving adequate prophylaxis (probability of benefit 0, 0.01, and 0.03 for 3, 4, and 5 risk factors). This was attenuated by weighting, with persistent benefit in 1 to 2 risk factors (probability of benefit 0.90 and 0.94) but equalization of risk in 3+ risk factors. CONCLUSIONS: Guideline-directed PONV prophylaxis is inconsistently associated with incidence of PONV across the guideline-defined risk spectrum. This phenomenon, and its attenuation with weighting, is consistent with 2 points: dichotomous risk-factor summation ignores differential effects of individual components, and prognostic information might exist beyond these risk factors. PONV risk at a given sum of risk factors is not homogeneous, but rather is determined by the unique composition of risk factors and other prognostic attributes. These differences appear to have been identified by clinicians, prompting use of more antiemetics. Even after accounting for these differences, however, addition of a third agent did not further reduce risk.

Procalcitonin levels in pregnancy: A systematic review and meta-analysis of observational studies.

BACKGROUND: The utility of procalcitonin to identify obstetric sepsis is unknown. OBJECTIVE: To calculate the mean (range) procalcitonin in pregnancy among healthy women not in labor (group 1), healthy women in labor (group 2), and women with preterm prelabor rupture of membranes (PPROM) without clinical chorioamnionitis (group 3). SEARCH STRATEGY: NLM PubMed, Elsevier Embase, and Wiley Cochrane Central Register of Controlled Trials from inception to February 21, 2022. SELECTION CRITERIA: Ten or more pregnant women with procalcitonin reported at more than 20 weeks of pregnancy, with information on labor, PPROM, and infection. Exclusions were major medical comorbidities. DATA COLLECTION AND ANALYSIS: Each abstract and full-text review was independently reviewed by the same two authors. Quality was reviewed using the Newcastle-Ottawa Scale. A meta-analysis was performed using a random effects model. MAIN RESULTS: The systematic review included 25 studies: 10 (40%) of good quality and 15 (60%) of poor quality. The meta-analysis included 21 studies. Mean procalcitonin in group 1 was 0.092 ng/mL (range 0.036-0.049 ng/mL), in group 2 it was 0.130 ng/mL (range 0.049-0.259 ng/mL), and in group 3 it was 0.345 ng/mL (range 0.005-1.292 ng/mL). CONCLUSIONS: Among healthy pregnant women not in labor, procalcitonin levels are comparable to those in non-pregnant adults and may be useful in identifying infection. Procalcitonin levels in other groups overlap abnormal values of procalcitonin in non-pregnant adults, and may not discriminate infection among women in labor or with obstetric comorbidities. PROSPERO: CRD42020157376, registered 4/28/2020.

Opioid-Sparing Multimodal Analgesia Use After Cesarean Delivery Under General Anesthesia: A Retrospective Cohort Study in 729 US Hospitals.

BACKGROUND: Optimizing analgesia after cesarean delivery is essential to quality of patient recovery. The American Society of Anesthesiologists and the Society for Obstetric Anesthesia and Perinatology recommend multimodal analgesia (MMA). However, little is known about clinical implementation of these guidelines after cesarean delivery under general anesthesia (GA). We performed this study to describe the use of MMA after cesarean delivery under GA in the United States and determine factors associated with use of MMA, variation in analgesia practice across hospitals, and trends in MMA use over time. METHODS: A retrospective cohort study of women over 18 years who had a cesarean delivery under GA between 2008 and 2018 was conducted using the Premier Healthcare database (Premier Inc). The primary outcome was utilization of opioid-sparing MMA (osMMA), defined as receipt of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen with or without opioids and without the use of an opioid-combination drug. Any use of either agent within a combination preparation was not considered osMMA. The secondary outcome was use of optimal opioid-sparing MMA (OosMMA), defined as use of a local anesthetic technique such as truncal block or local anesthetic infiltration in addition to osMMA. Mixed-effects logistic regression models were used to examine factors associated with use of osMMA, as well as variation across hospitals. RESULTS: A total of 130,946 patients were included in analysis. osMMA regimens were used in 11,133 patients (8.5%). Use of osMMA increased from 2.0% in 2008 to 18.8% in 2018. Black race (7.9% vs 9.3%; odds ratio [OR] [95% confidence interval {CI}] 0.87 [0.81-0.94]) and Hispanic ethnicity (8.6% vs 10.0%; OR, 0.86 [0.79-0.950]) were associated with less receipt of osMMA compared to White and non-Hispanic counterparts. Medical comorbidities were generally not associated with receipt of osMMA, although patients with preeclampsia were less likely to receive osMMA (9.0%; OR, 0.91 [0.85-0.98]), while those with a history of drug abuse (12.5%; OR, 1.42 [1.27-1.58]) were more likely to receive osMMA. There was moderate interhospital variability in the use of osMMA (intraclass correlation coefficient = 38%). OosMMA was used in 2122 (1.6%) patients, and utilization increased from 0.8% in 2008 to 4.1% in 2018. CONCLUSIONS: Variation in osMMA utilization was observed after cesarean delivery under GA in this cohort of US hospitals. While increasing trends in utilization of osMMA and OosMMA are encouraging, there is need for increased attention to postoperative analgesia practices after GA for cesarean delivery given low percentage of patients receiving osMMA and OosMMA.

Maternal Cardiovascular Morbidity Events Following Preeclampsia: A Retrospective Cohort Study.

BACKGROUND: Patients with preeclampsia are at high risk for long-term cardiovascular events, yet the short-term, acute cardiovascular complications that follow preeclampsia are understudied. The objective of this study was to compare the short-term, acute maternal cardiovascular morbidity events after delivery among patients with a diagnosis of preeclampsia versus those without this diagnosis. METHODS: In this retrospective cohort study, the Premier inpatient database was used to examine a cohort of obstetric patients older than 18 years, who delivered from January 1, 2016, to September 30, 2020. A diagnosis of preeclampsia and preeclampsia with severe features during delivery hospitalization were the exposures of interest. The primary outcome was a composite of maternal cardiovascular morbidity events during delivery hospital admission. The secondary outcome was the occurrence of maternal cardiovascular morbidity events during a readmission within 90 days of delivery hospitalization. RESULTS: In total, 4,488,759 patients met inclusion criteria, of which 158,114 (3.5%) were diagnosed with preeclampsia without severe features, and 117,940 (2.6%) with preeclampsia with severe features. Adjusted odds of maternal cardiovascular morbidity events were higher in patients with preeclampsia and in those with preeclampsia with severe features compared with those without preeclampsia during delivery hospitalization (adjusted odds ratio [OR] [95% confidence interval {CI}] 1.87 [1.78-1.97] and 4.74 [4.44-5.05], respectively) and within 90 days (adjusted OR [95% CI] 2.01 [1.83-2.21] and 2.32 [2.10-2.57], respectively). CONCLUSIONS: Patients with both preeclampsia and preeclampsia with severe features have higher rates of maternal cardiovascular morbidity events than those without preeclampsia. Future studies are necessary to examine which patients with preeclampsia are at highest risk for cardiovascular complications.

Obstructive Sleep Apnea Among Gravidas With Chronic Hypertension Compared to Matched Controls: A Prospective Cohort Study.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Anesthesia and Analgesia for the Obese Parturient.

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.