Cardiovascular disease (CVD) is a leading cause of maternal mortality. Patients with newly diagnosed or decompensating CVD are at high risk of morbidity and mortality. Pregnancy heart teams (PHTs) allow for multidisciplinary management of the cardio-obstetric patient. Anesthesiologists are key members of the PHT. A cardio-obstetric patient's delivery plan should consider the pathophysiology of their lesion in the context of the hemodynamic changes that occur during pregnancy, labor, delivery, or termination, and the postpartum period. More research is needed to provide evidence-based guidance for the management of cardio-obstetric patients.

Background Preeclampsia is a serious pregnancy complication affecting 5% to 8% of pregnancies globally. preeclampsia is a leading cause of maternal and neonatal morbidity and death. Despite its prevalence, the underlying mechanisms of preeclampsia remain unclear. This study investigated the role of vasorin in preeclampsia pathogenesis by examining its levels in extracellular vesicles (EVs) and effects on vascular function. Methods and Results We conducted unbiased proteomics on urine‐derived EVs from women with severe preeclampsia and normotensive pregnancies, identifying differentially abundant proteins. Vasorin expression levels were measured in urinary EVs, plasma EVs, and placental tissue. EVs were generated from human and murine placental explants. Vascular functions were assessed using murine aortic rings and human aortic endothelial cells. Vasorin expression was manipulated in human aortic endothelial cells via overexpression and knockdown followed by RNA sequencing. One hundred twenty proteins showed ≥±1.5‐fold regulation (P<0.05) between severe preeclampsia and NTP. Vasorin levels decreased in severe preeclampsia in urinary EVs, plasma EVs, and placental tissue. Vasorin levels increased with gestational age in murine pregnancy and were diminished in a murine model of preeclampsia. Severe preeclampsia and murine preeclampsia EVs impaired human aortic endothelial cell migration and inhibited murine aortic ring vasorelaxation. Vasorin overexpression counteracted these effects. RNA sequencing showed that vasorin manipulation in human aortic endothelial cells differentially regulated hundreds of genes linked to vasculogenesis, proliferation, migration, and apoptosis. Conclusions The data suggest that vasorin, delivered to the endothelium via EVs, regulates vascular function and that the loss of EV vasorin may be one of the mechanistic drivers of preeclampsia.

Background: Preeclampsia (PE) significantly impacts maternal and perinatal health worldwide. Despite limited treatment options, predictive tests could help in early diagnosis and personalized treatment/prevention strategies. Current biomarker, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PIGF) offer reasonable negative predictive values, but their use as positive predictive markers is limited. Using unbiased discovery proteomics on urine extracellular vesicles (EV), followed by verification by ELISA and western blotting we identified a novel biomarker candidate for PE, vasorin (VASN), which is significantly decreased in PE, along with a known mediator of PE, angiotensinogen (AGT), that was significantly increased in PE as biomarker candidates. Hypothesis: Levels of AGT, VASN and their ratios in peripheral blood can be utilized as biomarkers for PE. Goals/Aims: 1) To determine gestational age (GA)-dependence of AGT, VASN and AGT/VASN plasma levels in human and murine pregnancy. 2) To assess disease association of AGT, VASN and AGT/VASN in a cohort of pregnant women with PE with severe features (sPE) and gestational age-matched normotensive pregnant women (NTP) and in a murine model of PE. Methods: Plasma was collected from GA-matched NTP and sPE. Timed pregnant mice were injected with adenoviral vector (AD) encoding sFLT-1 on embryonic day 10.5 (mouse PE), or with AD encoding enhanced green fluorescent protein injection (mouse control). AGT and VASN were measured by ELISA in human samples and were quantified by western blotting in murine samples. Results: AGT and AGT/VASN showed negative correlations with GA, while VASN levels showed positive correlation with GA in NTP and in mouse controls. PlGF and sFLT-1 levels had weak/no correlations with GA. AGT and AGT/VASN were significantly higher in sPE and mouse PE, while VASN was significantly decreased in sPE and mouse PE as compared to NTP and mouse controls, respectively. To differentiate between sPE vs NTP with receiver operating characteristic curve (ROC) for AGT/VASN: AUC (0.90), Sensitivity =92%, Specificity = 85% at AGT/VASN>81.6. Conclusion: AGT and AGT/VASN ratio increase, and VASN decrease can serve as biomarkers for PE.

Introduction Quadratus lumborum (QL) block has previously been shown to provide improved analgesia in patientsundergoing primary total hip arthroplasty (THA) under spinal anesthesia when compared to spinalanesthesia alone. Additionally, recent studies have shown the addition of intrathecal morphine (ITM) toprovide superior postoperative analgesia in patients undergoing various surgical interventions includingtotal knee arthroplasty under spinal anesthesia with peripheral nerve blockade. At this time, however, therehas not been a study evaluating the effects of intrathecal morphine in patients undergoing THA under spinalanesthesia with QL block. This study aims to assess if the addition of intrathecal morphine can provideadequate or even superior postoperative analgesia in patients undergoing primary THA. Methods This retrospective study included 26 patients in the spinal/QL block/intrathecal morphine (SA+QLB+ITM)group, 31 patients in the spinal/QL block group (SA+QLB), and 28 patients in the spinal only (SA or control)group. Twenty-six patients undergoing primary THA under a combination of spinal anesthesia andperipheral nerve blockade (quadratus lumborum block) were given a dose of 100 mcg of intrathecalmorphine. Various parameters were evaluated including Post-Anesthesia Care Unit (PACU) and 24-hourvisual analog scale (VAS) scores, time to first opioid use, 24- and 48-hour total opioid use as oral morphineequivalents (OME), 24-hour ambulation distance, and time from block placement to hospital discharge. Theresults were analyzed and compared to patients undergoing primary THA under spinal anesthesia with QLblock (no intrathecal morphine) and compared to a control group of patients undergoing primary THA underspinal anesthesia only. Results The study analysis included 26 patients in the SA+QLB+ITM group, 31 patients in the SA+QLB group, and 28patients in the SA (control) group. When compared with the control group, the SA+QLB+ITM had lower 24-hour total opioid usage (mean difference 20.80 OME, CI 6.454 to 35.15, p-value 0.0025), longer time to 1stopioid use (mean difference -20.51 hours later, p-value .0052), lower 24-hr VAS (difference 2.421, p-value0.0012, CI 0.8559 to 3.987), and faster time to discharge (16.00 hr earlier, p-value 0.0459). When comparedto the SA+QLB group, the SA+QLB+ITM group only showed a statistically significant difference in faster timeto discharge (19.46 hr earlier, p-value 0.0068). However, while there was no statistically significantdifference in time to 1st opioid use between the control and SA+QLB group, the difference did becomesignificant when comparing the control to the SA+QLB+ITM group (mean difference -20.51 hours later (p-value .0052). There was no significant difference in either of the three groups in ambulation distance at 24hours, PACU VAS, or 48-hour total opioid use. Conclusion Our study concludes that the addition of 100 mcg ITM for total hip arthroplasty under spinal anesthesiaimproved postoperative analgesia compared to the control group. Also, the ITM group did better withrespect to delay in first opioid use and decreased hospital stay compared to the control and block-onlygroups. Our study warrants no more concerns of PONV, pruritus, or respiratory depression with this dose ofITM and requires standard postoperative care

Cardiovascular disease (>25%) is the leading cause of death among pregnant women in the United States. This chapter covers risk stratification, pathophysiology, and anesthetic management of women with specific cardiac diseases. In the last decade, advances in treatment and management of cardiac disease in the pregnant patient have led to improvements in survival of obstetric patients with known cardiac disease. Key to the improvements in care is the creation of Pregnancy Heart Teams, multidisciplinary teams with knowledge and experience caring for the obstetric patient with cardiovascular disease. Cardiovascular disease encompasses a heterogeneous group of lesions with differing hemodynamic goals, management and risks during pregnancy, delivery, and postpartum. The anesthesiologist is best able to care for these women by understanding the specific cardiovascular lesion, a woman's current status, the obstetric and fetal considerations and the impact of anesthetic techniques.

A thoroughly revised third edition of the acclaimed textbook for caregivers involved in the management of pregnant women with uncommon diseases or an unusual or rare condition. The book offers valuable case reports and experience collated by an international team of editors and contributors who are leading experts in the field. This edition contains five additional chapters covering topics like cardiac and neuraxial point of care ultrasound, substance abuse, rare inherited conditions, and anesthesia for rare fetal and placental conditions. Clear, concise management guidelines and algorithms are provided, and each chapter is written from the viewpoint of the obstetric anesthesiologist. Numerous tables, figures and photographs provide visual aids and each chapter contains valuable clinical insights highlighting the essential facts. Featuring updated figures and references, links to useful websites for further reading and a list of commonly used abbreviations. A valuable resource for obstetric anesthetists, perinatologists and other obstetric care providers.

Background and purpose of the study Intrathecal morphine (ITM) provides effective postoperative analgesia in patients undergoing total knee arthroplasty (TKA) under spinal anesthesia. However, the ideal dose at which maximal analgesic effects can be delivered with minimal side effects is not clearly known. This retrospective study is aimed to compare two different doses of ITM with respect to analgesia benefits and side effects. Methods This is a retrospective, descriptive, single-center study approved by the Institutional Review Board (IRB) at the University of Alabama at Birmingham. Three patient groups were selected: a control group receiving continuous adductor canal block (CCACB) under spinal anesthesia, and two experimental groups receiving single-dose adductor canal block (SSACB) under spinal anesthesia with either 100 mcg or 150 mcg of ITM. The sample size included 75 patients (25 per group) who were 18 years and older, American Society of Anesthesiology (ASA) class 1-3 who were undergoing primary TKA. Patients with chronic pain or opioid use exceeding 30 days and those undergoing surgeries other than primary TKA were excluded. Outcome data, including opioid use (from which post-operative oral morphine equivalents (OME) were calculated), antiemetic use, visual analog pain scale (VAS) scores, distance ambulated at 24 hours, and length of hospital stay, were extracted by chart review. Results In the post-anesthesia care unit (PACU), patients in both ITM groups experienced significantly lower opioid consumption and pain scores compared to the control group (p<.001). Furthermore, cumulative OME at 24 hours was significantly less in the ITM groups compared to the control, but there was no difference between ITM doses (p=0.004; mean cumulative OME for control was 77.2 OME vs 43.4 OME for 100 mcg ITM vs 42.6 OME for 150 mcg ITM). Antiemetic usage did not increase in the ITM groups. Although there was no statistically significant difference in ambulation at 24 hours, both ITM groups exhibited a trend toward greater average ambulation distance compared to the control group (p=0.095; mean distance walked for control was 67.6 feet, 76.6 feet for 100 mcg ITM vs 98.8 feet for 150 mcg ITM). Hospital length of stay did not significantly differ between the groups. Conclusion ITM doses of 100 mcg and 150 mcg provide effective analgesia for patients undergoing lower extremity total knee arthroplasty under spinal anesthesia. Patients receiving ITM had better pain scores in the immediate post-operative period and had overall less oral morphine equivalent consumption when compared to control. In addition, the safety and side effect profile for ITM is similar for both doses as there was no incidence of respiratory depression and antiemetic usage did not differ between all study arms. Future studies should explore the use of higher ITM doses and consider a broader patient population to further understand the advantages and potential drawbacks of ITM in TKA surgery.

Purpose of Review This review of neuraxial anesthesia in high-risk cardiac patients aims to delineate current best practices and highlight emerging themes in the literature. Recent Findings Pregnancy, especially in the presence of cardiac comorbidities, poses a unique set of challenges for anesthesiologists and obstetricians. Vaginal delivery, with good neuraxial anesthesia, is usually the preferred mode of delivery in women with cardiac disease, although the rate of cesarean delivery is higher among women with heart disease. For obstetric procedures, recent case reports have demonstrated the safety of neuraxial anesthesia in high-risk cardiac patients, though providers necessitate a careful balance between adequate neuraxial anesthesia and hemodynamic compromise. Summary Neuraxial anesthesia, including epidural and spinal techniques, has become a cornerstone in the management of labor pain and cesarean deliveries. However, its application in high-risk cardiac pregnant patients demands a careful consideration of potential risks and benefits.

An intra-aortic balloon pump (IABP) may be placed preoperatively for high-risk patients with reduced ejection fraction or multivessel coronary disease undergoing non-cardiac surgery. Dexmedetomidine (DEX) has both anesthetic and cardioprotective effects, and little evidence is present on its effect on minimum alveolar concentration (MAC) and bispectral index (BIS). We present the case of a high-risk cardiac patient who was admitted and required fluid optimization prior to coronary artery bypass grafting (CABG). An IABP was placed after failure to tolerate intermittent hemodialysis (iHD). Bowel ischemia complicated this patient's course, necessitating an urgent exploratory laparotomy with the IABP in place. DEX and 0.3-MAC sevoflurane were successfully used without perioperative cardiac complications. Continuous BIS monitoring was performed to maintain an adequate level of anesthesia. DEX should be considered as an alternative anesthetic adjuvant in high-risk and medically complex patients.

Differential diagnosis of the underlying cause of new-onset total body paralysis can be challenging and unsatisfying. In akinetic mutism, a rare side effect of tacrolimus, patients become apathetic, mute, and lose voluntary muscle movement. Epidural subarachnoid migration can present with similar symptoms. Delayed emergence/paralysis after anesthesia can include the common culprits of residual operative medications, stroke, as well as tacrolimus-induced akinetic mutism and thoracic epidural migration. We present a case of new-onset total body paralysis, presenting on postoperative day 1 following a double-lung transplant in a patient started on tacrolimus with a thoracic epidural catheter in place.

Neuraxial anesthesia is preferred over general anesthesia in obstetric patients to avoid airway manipulation, aspiration, and maternal-fetal transfer of medications; however, a sudden sympathetic block is generally avoided in patients with hypertrophic obstructive cardiomyopathy (HOCM). The case of a 31-year-old G2P0010 with HOCM with severe resting left ventricular outflow tract (LVOT) obstruction and systolic anterior motion of the mitral valve undergoing a cerclage under choroprocaine spinal anesthesia is presented. Risks and benefits of general versus neuraxial anesthesia, and epidural versus spinal anesthesia, in this specific setting are reviewed.

Background: We recently demonstrated that placenta-derived extracellular vesicles (pEVs) cargo play a role in vascular dysfunction in patients with severe preeclampsia (sPE). We focused our follow up studies on a novel protein vasorin (VASN) that has not as yet been studied in PE. Here, we hypothesize that decreased VASN in EVs cargo plays a significant role in the regulation of vascular endothelial proliferation and function in sPE. Methods: We manipulated VASN by overexpression and knockdown in human aortic endothelial cells (HAEC) and in murine aortic vascular rings (MVR) using adenoviral vectors encoding VASN (AD-VASN) or VASN shRNA (AD-shVASN), respectively. VASN levels in EVs, in HAEC and in MVR with/wo adenoviral overexpression or knockdown of VASN was done by western blotting. Migration of HAEC was studied by a scratch and repair migration assay and contractile function of MVR was assessed by wire myography. A PE-like vascular dysfunction was produced in timed pregnant mice by intravenous injection of an adenoviral vector encoding the short form of FMS-like tyrosine kinase 1 (sFLT-1) on embryonic day 10.5 (E10.5) of pregnancy. Plasma from sFLT-1 -injected and control untreated (UT) mice were collected on E15.5,E17.5 and E19.5. Results: We confirmed our findings with proteomics and using western blotting we detected a significant reduction in VASN levels in both urinary and plasma-derived EVs in sPE patients when compared to normotensive. Moreover, we detected a time-dependent significant reduction of VASN in EVs from plasma of sFLT-1 injected mice whereas UT mice exhibited a time-dependent increase of VASN. Western blotting also confirmed over-expression and knock down of VASN in HAEC and in MVR treated with AD-VASN and AD-shVASN, respectively. Treatment of HAEC with EVs from sPE, but not by EVs from NTP inhibited migration, and pretreatment with AD-VASN but not with AD-shVASN rescued migration upon treatment with EVs from PE. Treatment of MVR with EVs from sPE, but not by EVs from NTP inhibited acetylcholine (ACh)-induced vasorelaxation. Pretreatment with AD-VASN, but not with AD-shVASN rescued ACh-induced vasorelaxation upon treatment with EVs from sPE. Conclusion: Over-expression of VASN using adenoviral vectors rescued inhibitory effects of EVs from sPE on migration of HAEC and ACh-induced vasorelaxation in MVR, suggesting that reduced VASN content in EVs from sPE plays a mechanistic role in vascular dysfunction observed in sPE.

BACKGROUND: Preeclampsia (PE) manifesting as hypertension and organ injury is mediated by vascular dysfunction. In biological fluids, extracellular vesicles (EVs) containing microRNA (miRNA), protein, and other cargo released from the placenta may serve as carriers to propagate injury, altering the functional phenotype of endothelial cells. PE has been consistently correlated with increased levels of placenta-derived EVs (pEVs) in maternal circulation. However, whether pEVs impaired endothelial cell function remains to be determined. In this study, we hypothesize that pEVs from pregnant women with severe PE (sPE) impair endothelial function through altered cell signaling. METHODS: We obtained plasma samples from women with sPE (n = 14) and normotensive pregnant women (n = 15) for the isolation of EVs. The total number of EV and pEV contribution was determined by quantifying immunoreactive EV-cluster of designation 63 (CD63) and placental alkaline phosphatase (PLAP) as placenta-specific markers, respectively. Vascular endothelial functional assays were determined by cell migration, electric cell-substrate impedance sensing in human aortic endothelial cells (HAECs), and wire myography in isolated blood vessels, preincubated with EVs from normotensive and sPE women. RESULTS: Plasma EV and pEV levels were increased in sPE when compared to normotensive without a significant size distribution difference in sPE (108.8 ± 30.2 nm) and normotensive-EVs (101.3 ± 20.3 nm). Impaired endothelial repair and proliferation, reduced endothelial barrier function, reduced endothelial-dependent vasorelaxation, and decreased nitrite level indicate that sPE-EVs induced vascular endothelial dysfunction. Moreover, sPE-EVs significantly downregulated endothelial nitric oxide synthase (eNOS and p-eNOS) when compared to normotensive-EV. CONCLUSIONS: EVs from sPE women impair endothelial-dependent vascular functions in vitro.

Background: We recently demonstrated that placenta-derived extracellular vesicles (pEVs) cargo play a role in vascular dysfunction in patients with severe preeclampsia (sPE). We focused our follow up studies on a novel protein vasorin (VASN) that has not as yet been studied in PE. Here, we hypothesize that decreased VASN in EVs cargo plays a significant role in the regulation of vascular endothelial proliferation and function in sPE. Methods: We manipulated VASN by overexpression and knockdown in human aortic endothelial cells (HAEC) and in murine aortic vascular rings (MVR) using adenoviral vectors encoding VASN (AD-VASN) or VASN shRNA (AD-shVASN), respectively. VASN levels in EVs, in HAEC and in MVR with/wo adenoviral overexpression or knockdown of VASN was done by western blotting. Migration of HAEC was studied by a scratch and repair migration assay and contractile function of MVR was assessed by wire myography. A PE-like vascular dysfunction was produced in timed pregnant mice by intravenous injection of an adenoviral vector encoding the short form of FMS-like tyrosine kinase 1 (sFLT-1) on embryonic day 10.5 (E10.5) of pregnancy. Plasma from sFLT-1 -injected and control untreated (UT) mice were collected on E15.5,E17.5 and E19.5. Results: We confirmed our findings with proteomics and using western blotting we detected a significant reduction in VASN levels in both urinary and plasma-derived EVs in sPE patients when compared to normotensive. Moreover, we detected a time-dependent significant reduction of VASN in EVs from plasma of sFLT-1 injected mice whereas UT mice exhibited a time-dependent increase of VASN. Western blotting also confirmed over-expression and knock down of VASN in HAEC and in MVR treated with AD-VASN and AD-shVASN, respectively. Treatment of HAEC with EVs from sPE, but not by EVs from NTP inhibited migration, and pretreatment with AD-VASN but not with AD-shVASN rescued migration upon treatment with EVs from PE. Treatment of MVR with EVs from sPE, but not by EVs from NTP inhibited acetylcholine (ACh)-induced vasorelaxation. Pretreatment with AD-VASN, but not with AD-shVASN rescued ACh-induced vasorelaxation upon treatment with EVs from sPE. Conclusion: Over-expression of VASN using adenoviral vectors rescued inhibitory effects of EVs from sPE on migration of HAEC and ACh-induced vasorelaxation in MVR, suggesting that reduced VASN content in EVs from sPE plays a mechanistic role in vascular dysfunction observed in sPE.

External cephalic version (ECV) has been successfully utilized to reduce breech presentations at term and offers an alternative to elective cesarean delivery. Unfortunately, there is not a consensus on which type of regional anesthesia conveys the highest chances for a successful ECV. This case report describes the use of the epidural volume extension technique to provide surgical anesthesia for ECV with a reduced dose of local anesthetic, with the goals of minimizing motor block and hypotension in the setting of an outpatient procedure.

Purpose of review The aim of this review of cardiac disease in pregnancy is to delineate current best practices and highlight emerging themes in the literature. Recent findings Cardiovascular disease is the leading cause of death among pregnant women in the United States. Many clinicians and institutions have developed care pathways to approach care in these high-risk patients including highly coordinated multidisciplinary teams. The diagnosis of pulmonary hypertension is the greatest risk factor for an adverse event in pregnant women. Vaginal delivery, with good neuraxial anesthesia, is usually the preferred mode of delivery in women with cardiac disease, although the rate of cesarean delivery is higher among women with heart disease. Summary The leading cause of morbidity and mortality in pregnant women is cardiac disease. Preconception counseling is useful for optimizing patients for pregnancy and setting appropriate expectations about care and outcomes. Ensuring that women are cared for in centers with appropriate multidisciplinary resources is key for improving outcomes for cardio-obstetric patients.

Management of the pregnant patient requiring neurosurgery poses multiple challenges, juxtaposing pregnancy-specific considerations with that accompanying the safe provision of intracranial or spine surgery. There are no specific evidence-based recommendations, and case-by-case interdisciplinary discussions will guide informed decision-making about the timing of delivery vis-à-vis neurosurgery, the performance of cesarean delivery immediately before neurosurgery, consequences of neurosurgery on subsequent delivery, or even the optimal anesthetic modality for neurosurgery and/or cesarean delivery. In general, identifying whether increased intracranial pressure poses a risk for herniation is crucial before allowing neuraxial procedures. Modified rapid sequence induction with advanced airway approaches (videolaryngoscopic or fiberoptic) allows improved airway manipulation with reduced risks associated with endotracheal intubation of the obstetric airway. Currently, very few anesthetic drugs are avoided in the neurosurgical pregnant patient; however, ensuring access to critical care units for prolonged monitoring and assistance of the respiratory-compromised patient is necessary to ensure safe outcomes.