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Aims: Epidural opioids can provide effective analgesia for acute postoperative pain. Due to its unique physicochemical properties and long systemic elimination half‐life, epidural methadone may provide lasting analgesia with minimal adverse effects; however, human studies are lacking. The aim of the study was to test the hypothesis that epidural methadone would exhibit greater segmental analgesia (analgesia at the dermatome of injection vs. distant dermatomes) than epidural morphine. Methods: In a prospective, randomized, double‐blinded, crossover study, thirteen healthy volunteers received a 4‐mg epidural bolus of methadone or morphine at L3–L4 and underwent repeated assessment of dermatomal heat pain tolerance and pressure pain threshold at lumbar (L3) and trigeminal (V2) dermatomes, pupil diameter, respiratory parameters and venous opioid concentration for 24 h. The primary outcome was selective (lumbar vs. trigeminal) segmental analgesia for heat pain, as a marker of a spinal analgesic mechanism. Results: The degree of segmental analgesia to heat pain tolerance was not different between morphine and methadone (P =.09), although morphine (P =.0009) but not methadone (P =.81) produced significant analgesia to heat pain at the lumbar vs. trigeminal dermatome over 0–12 h. Morphine overall provided longer lasting analgesia to heat pain vs. methadone (24 vs. 2 h, respectively). Morphine elicited greater systemic effects, including miosis (P =.009) and opioid‐related adverse effects (P =.002). Conclusions: These results suggest that, with equal epidural doses, both methadone and morphine produced analgesia and methadone did not produce greater segmental effects than morphine. Epidural methadone provided a more favourable adverse effect profile. [ABSTRACT FROM AUTHOR]

Background: The leading causes of maternal mortality include respiratory failure, cardiovascular events, infections, and hemorrhages. The use of extracorporeal membrane oxygenation (ECMO) as rescue therapy in the peripartum period for cardiopulmonary failure is expanding in critical care medicine. Methods: This retrospective observational study was conducted on a nationwide cohort in Israel. During the 3‐year period, between September 1, 2019, and August 31, 2022, all women in the peripartum period who had been supported by ECMO for respiratory or circulatory failure at 10 large Israeli hospitals were identified. Indications for ECMO, maternal and neonatal outcomes, details of ECMO support, and complications were collected. Results: During the 3‐year study period, in Israel, there were 540 234 live births, and 28 obstetric patients were supported by ECMO, with an incidence of 5.2 cases per 100 000 or 1 case per 19 000 births (when excluding patients with COVID‐19, the incidence will be 2.5 cases per 100 000 births). Of these, 25 were during the postpartum period, of which 16 (64%) were connected in the PPD1, and 3 were during pregnancy. Eighteen patients (64.3%) were supported by V‐V ECMO, 9 (32.1%) by V‐A ECMO, and one (3.6%) by a VV‐A configuration. Hypoxic respiratory failure (ARDS) was the most common indication for ECMO, observed in 21 patients (75%). COVID‐19 was the cause of ARDS in 15 (53.7%) patients. The indications for the V‐A configuration were cardiomyopathy (3 patients), amniotic fluid embolism (2 patients), sepsis, and pulmonary hypertension. The maternal and fetal survival rates were 89.3% (n = 25) and 100% (n = 28). The average ECMO duration was 17.6 ± 18.6 days and the ICU stay was 29.8 ± 23.8 days. Major bleeding complications requiring surgical intervention were observed in one patient. Conclusions: The incidence of using ECMO in the peripartum period is low. The maternal and neonatal survival rates in patients treated with ECMO are high. These results show that ECMO remains an important treatment option for obstetric patients with respiratory and/or cardiopulmonary failure. [ABSTRACT FROM AUTHOR]

A key unresolved controversy in severe COVID-19 pneumonitis in pregnancy is the optimum timing of delivery and whether delivery improves or worsens maternal outcomes. We aimed to assess clinical data on every intensive care unit (ICU) day for pregnant and postpartum women admitted to the ICU with COVID-19, with a particular focus on the days preceding and following delivery. In this multicentre, nationwide, prospective and retrospective cohort study, we evaluated all pregnant women who were admitted to an ICU in Israel with severe COVID-19 pneumonitis from the 13th week of gestation to the 1st week postpartum. We excluded pregnant patients in which the ICU admission was unrelated to severe COVID-19 pneumonitis. We assessed maternal and neonatal outcomes and longitudinal clinical and laboratory ICU data. The primary overall outcome was maternal outcome (worst of the following: no invasive positive pressure ventilation [IPPV], use of IPPV, use of extracorporeal membrane oxygenation [ECMO], or death). The primary longitudinal outcome was Sequential Organ Failure Assessment (SOFA) score, and the secondary longitudinal outcome was the novel PORCH (positive end-expiratory pressure [PEEP], oxygenation, respiratory support, chest x-ray, haemodynamic support) score. Patients were classified into four groups: no-delivery (pregnant at admission and no delivery during the ICU stay), postpartum (ICU admission ≥1 day after delivery), delivery-critical (pregnant at admission and receiving or at high risk of requiring IPPV at the time of delivery), or delivery-non-critical (pregnant at admission and not critically ill at the time of delivery). From Feb 1, 2020, to Jan 31, 2022, 84 patients were analysed: 34 patients in the no-delivery group, four in postpartum, 32 in delivery-critical, and 14 in delivery-non-critical. The delivery-critical and postpartum groups had worse outcomes than the other groups: 26 (81%) of 32 patients in the delivery-critical group and four (100%) of four patients in the postpartum group required IPPV; 12 (38%) and three (75%) patients required ECMO, and one (3%) and two (50%) patients died, respectively. The delivery-non-critical and no-delivery groups had far better outcomes than other groups: six (18%) of 34 patients and two (14%) of 14 patients required IPPV, respectively; no patients required ECMO or died. Oxygen saturation (SpO 2), SpO 2 to fraction of inspired oxygen (FiO 2) ratio (S/F ratio), partial pressure of arterial oxygen to FiO 2 ratio (P/F ratio), ROX index (S/F ratio divided by respiratory rate), and SOFA and PORCH scores were all highly predictive for adverse maternal outcome (p<0·0001). The delivery-critical group deteriorated on the day of delivery, continued to deteriorate throughout the ICU stay, and took longer to recover (ICU duration, Mantel-Cox p<0·0001), whereas the delivery-non-critical group improved rapidly following delivery. The day of delivery was a significant covariate for PORCH (p<0·0001) but not SOFA (p=0·09) scores. In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation. None. [ABSTRACT FROM AUTHOR]

Objective: Several reports of obstetric anesthesia management have been published since the onset of the COVID-19 pandemic. We aimed to collect high-quality broad and detailed data from different university medical centers in several European Society of Anesthesiologist countries. Methods: This prospective observational survey was performed in eight medical centers in Spain, Israel and Portugal from 1st April to 31st July 2020. Institutional review board approval was received at each participating center. Inclusion criteria: all women with a positive test for COVID-19. Retrieved data included maternal, delivery, anesthetic, postpartum details, and neonatal outcomes. Descriptive data are presented, and outcomes were compared for women with versus without respiratory signs and symptoms. Results: Women with respiratory symptoms (20/12.1%) had significantly higher mean (standard deviation) temperature (37.2 C (0.8) versus 36.8 C (0.6)), were older (34.1 (6.7) years versus 30.5 (6.6)) and had higher body mass index kg m-2 – (29.5 (7.5) versus 28.2 (5.1)). Women with respiratory symptoms delivered at a significantly earlier gestational age (50% < 37 weeks) with a 65% cesarean delivery rate (versus 22.1% in the group without respiratory symptoms) and 5- fold increased rate of emergency cesarean delivery, 30% performed under general anesthesia. A higher rate of intrauterine fetal death (3%) was observed than expected from the literature (0.2–0.3%) in developed countries. There was no evidence of viral vertical transmission. Conclusion: Well-functioning neuraxial analgesia should be available to manage laboring women with respiratory symptoms, as there is a higher frequency of emergency cesarean delivery. We report a higher rate of undiagnosed parturient and intrauterine fetal death. [ABSTRACT FROM AUTHOR]

Abstract Background Obstetric anesthesia workload demand in Israel has increased due to both an increase in the requests for labor analgesia and a marked increase in the cesarean delivery rate. We propose a new workload-driven performance indicator, the Obstetric Anesthesia Activity Index (OAAI), to serve as a single denominator of obstetric anesthesia activity to enable direct comparison of different hospitals despite dissimilar rates of epidural labor analgesia and cesarean delivery. Methods We performed a secondary analysis of two recent national surveys by the Israel Association of Obstetric Anesthesia. In 2005 and 2007 questionnaires were sent to all Israeli hospitals requesting information on the total numbers of deliveries, epidurals, and cesareans annually, together with the anesthesia workforce allocated for the provision of obstetric anesthesia services. The OAAI was calculated based on the premise that epidurals and cesareans are the predominant determinants of obstetric anesthesia workload and that a typical epidural takes about half the time of a typical cesarean. Accordingly, the OAAI for each hospital was calculated as ((0.75 * number of epidurals per year) + (1.5 * number of cesareans per year))/365. Results This secondary analysis assessed the 25 maternity units in Israel that participated in both the 2005 and 2007 surveys. As expected, there was a wide inter-hospital variability in epidural and cesarean rates. Hospital rankings based on annual delivery numbers were different from those based on the OAAI. The OAAI correlated closely both with the number of epidurals (2005: Pearson 0.97, p p p p Conclusions As there was such a wide range of demand for different obstetric anesthesia services among different hospitals, the total number of deliveries is a poor summary indicator of obstetric anesthesia workload. The calculated OAAI better reflected the obstetric anesthesia workload as a single denominator of activity.

Introduction: Brief hypercapnic challenge causes acute placental hypoperfusion with fetal brain sparing on BOLD-MRI. We hypothesize that this non-invasive imaging strategy can distinguish between normal pregnancy and chronic placental hypoperfusion (using the maternal hypoxia model).Methods: Eighteen pregnant female ICR mice were randomized to three groups: normoxia, late-onset hypoxia (12%O2;E13.5-17.5) and early-onset hypoxia (12%O2;E10.5-17.5). On E17.5, animals were imaged in a 4.7-T Bruker-Biospec MRI scanner. Fast coronal True-FISP was performed to identify organs of interest (placenta and fetal heart, liver and brain). BOLD-MRI was performed at baseline and during a 4-min hypercapnic challenge (5%CO2). %-change in placental and fetal signal was analyzed from T2*-weighted gradient echo MR images. Following MRI, fetuses and placentas were harvested, weighed and immuno-stained.Results: In normoxic mice, hypercapnia caused reduction in BOLD-MRI signal in placenta (-44% ± 7%; p < 0.0001), fetal liver (-32% ± 7%; p < 0.0001) and fetal heart (-54% ± 12%; p < 0.002), with relative fetal brain sparing (-12% ± 5%; p < 0.0001). These changes were markedly attenuated in both hypoxia groups. Baseline fetal brain/placenta SI ratio was highest in normoxic mice (1.14 ± 0.017) and reduced with increasing duration of hypoxia (late-onset hypoxia: 1.00 ± 0.026; early-onset hypoxia: 0.91 ± 0.016; p = 0.02). Both hypoxic groups exhibited fetal growth restriction with prominent placental glycogen-containing cells, particularly in early-onset hypoxia. There was increased fetal neuro- and intestinal-apoptosis in early-onset hypoxia only.Conclusions: BOLD-MRI with brief hypercapnic challenge distinguished between normoxia and both hypoxia groups, while fetal neuroapoptosis was only observed after early-onset hypoxia. This suggests that BOLD-MRI with hypercapnic challenge can identify chronic fetal asphyxia before the onset of irreversible brain injury. [ABSTRACT FROM AUTHOR]

Normal human pregnancy requires a dramatic increase in uteroplacental blood flow, which is achieved by a transformation in the geometry of uterine spiral arteries, a key element in this blood supply system. The transformation is mediated by trophoblast invasion directed at converting a portion of the spiral artery into an open funnel, thereby greatly reducing resistance to flow. The converted portion lies within the depth of the decidua and part of the myometrium. Insufficient depth of trophoblast invasion in early pregnancy predisposes to inadequate perfusion of the developing placenta and fetus and may lead to preeclampsia, fetal growth restriction, and preterm delivery, sometimes referred to as the “Great Obstetrical Syndromes”. We examine the hemodynamic consequences of spiral artery transformation in human pregnancy and the relationship between the degree of transformation and the corresponding change in flow rate and resistance to flow. We identify two key variables in determining the hemodynamic change: the longitudinal converted fraction of the spiral artery and the relative downstream diameter of the open funnel. Our results indicate that there is a critical threshold in the value of the converted fraction required to achieve the marked increase in uteroplacental blood flow in normal pregnancy. This finding validates common clinical observations that the depth of trophoblast invasion reflects the “adequacy” of the increase in uteroplacental blood supply required in normal human pregnancy. Our results provide a quantitative measure of that adequacy and may serve as a future diagnostic marker for high-risk pregnancy. NEW & NOTEWORTHY Human pregnancy requires dramatic increase in uteroplacental blood supply achieved by geometric transformation of uterine spiral arteries and facilitated by trophoblast invasion of these arteries to greatly reduce resistance to flow. Incomplete transformation has been associated with failed pregnancies, preeclampsia, and other pathologies, but a quantitative measure of “incompleteness” has been unavailable so far. We use a mathematical model to obtain a numerical threshold for this measure which may serve as a future diagnostic marker. [ABSTRACT FROM AUTHOR]

Background: Women may be unaware of the potential impact on subsequent deliveries of the decision to undergo primary breech cesarean (PBC) delivery rather than attempt external cephalic version (ECV). We investigated cesarean delivery rates and adverse maternal outcomes in the subsequent delivery following management of breech presentation by ECV versus PBC.Methods: This retrospective study identified women who delivered subsequent to breech presentation managed by attempted ECV or PBC. We assessed cesarean delivery rates and adverse maternal outcomes including hemorrhage, placental complications, infection, and obstetric complications in the subsequent delivery following attempted ECV versus PBC.Results: We identified 307 women who had attempted ECV and 508 with PBC in the index breech pregnancy. Following attempted ECV, 47 (15.3%) women had cesarean delivery in the subsequent pregnancy versus 246 (48.4%) following PBC, adjusted OR 0.24, 95% CI 0.16-0.35 for subsequent cesarean delivery after attempted ECV in the index pregnancy. The frequency of composite adverse outcomes related to cesarean delivery was 30 (9.8%) following attempted ECV versus 104 (20.5%) after PBC, p < .0001. The frequency of composite severe adverse maternal outcome was similar following attempted ECV 25 (8.8%) versus PBC 59 (11.9%).Conclusions: The current study suggests that attempted external cephalic version was associated with a five-fold decrease risk to undergo cesarean in the subsequent delivery and a significantly decreased frequency of composite adverse outcomes related to cesarean delivery in the subsequent delivery. [ABSTRACT FROM AUTHOR]

Introduction: We previously reported blood oxygen level dependent MRI (BOLD-MRI) for monitoring placental and fetal hemodynamic changes in mice following maternal hypercapnia. Here we use BOLD-MRI to compare the placental and fetal hemodynamic effects of different maternal vasopressors in mice.Methods: Pregnant ICR mice (n = 16; E17.5) anesthetized with pentobarbital (80 mg/kg i.p.) were placed supine in a 4.7-T Bruker Biospec MRI. Following baseline images, equipotential doses of ephedrine (10 mg/kg) or phenylephrine (10mcg/kg) were administered intravenously. Changes in placental and fetal signal were analyzed from T2*-weighted gradient echo MR images (TR/TE = 147/10 ms). Different regions of interest (placenta, fetal heart, fetal liver and fetal brain) were identified. Percentage change of BOLD-MRI signal intensity (SI) were presented as time curves.Results: Ephedrine and phenylephrine elicited markedly different effects. Phenylephrine caused an approximate 50% reduction in placental, fetal heart and fetal liver BOLD-MRI-SI, but fetal brain BOLD-MRI-SI was unchanged (statistically different from placenta and other fetal organs; p < 0.001), and the fetal brain/liver BOLD-MRI-SI ratio was markedly increased versus baseline (p < 0.001). Following ephedrine, placental BOLD-MRI-SI increased 30% and fetal heart BOLD-MRI-SI was reduced 26%; other fetal organs were unchanged. Blood gases were unchanged.Discussion: Phenylephrine induced BOLD-MRI-SI changes suggestive of placental and fetal hypoperfusion with brain sparing. Ephedrine induced BOLD-MRI-SI changes suggestive of increased cardiac output; we speculate that reduced fetal heart BOLD-MRI-SI may be due to increased fetal myocardial oxygen extraction or metabolic acidosis. The result demonstrates the potential of BOLD-MRI as a non-invasive hemodynamic tool for assessing pharmacodynamics effects in the placental and fetus. [ABSTRACT FROM AUTHOR]

Background: The coiled geometry of spiral arteries in the human uteroplacental circulation is a hemodynamic enigma because of added length of a spiral artery compared with that of a straight artery, as well as added complexity of the flow within the vessel because of the coiling curvature.Methods: We examined the geometric and hemodynamic characteristics of mathematically defined helical and spiral arteries and compared these with the corresponding characteristics of a straight artery traversing the same depth of tissue, with the aim of gaining some insight into the possible role of spiral geometry in uteroplacental perfusion.Results: The results indicate that the added length of a spiral artery provides the uteroplacental circulation with a reserve of high resistance to flow. The effect of coiling geometry on the flow within the artery is the development of churning vortices in planes normal (perpendicular) to the main flow direction.Conclusions: In the early stages of pregnancy the reserve of high resistance is intact, thus keeping blood supply low. As pregnancy progresses, the reserve is gradually purged by trophoblast invasion and transformation of the distal portion of the spiral artery into an open funnel, thus providing the required high blood supply. The development of churning vortices within the spiral artery support earlier suggestions in the literature that the "spurts" of maternal blood emerging from these arteries may play a role in shaping the anatomy of the villous trees among placental lobules. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated changes in placental and fetal hemodynamics in rodents during acute hypercapnia using BOLD-MRI and Doppler ultrasound.Methods: Animals were anesthetized with pentobarbital and, in consecutive 4-min periods, breathed: air, 21%O2:5%CO2, and 95%O2:5%CO2.Bold-mri: Pregnant ICR mice (n = 6; E17.5) were scanned in a 4.7-T Bruker Biospec spectrometer. Placenta and fetal liver, heart and brain were identified on True-FISP images. Percent change in signal intensity (SI) were analyzed every 30 s from T2*-weighted GE images (TR/TE = 147/10 ms). Doppler: Pregnant Wistar rats (n = 6; E18-20) were anesthetized with pentobarbital and received abdominal Doppler ultrasound. Umbilical artery pulsatility index (PI) and fetal heart rate were assessed at baseline and after two minutes of both hypercapnic challenges.Results: BOLD-MRI: Normoxic-hypercapnia caused immediate marked reduction in SI in placenta (-44% ± 5.5; p < 0.001), fetal liver (-32% ± 6.4; p < 0.001) and fetal heart (-53% ± 9.9; p < 0.001) but only minor changes in fetal brain (-13% ± 3.4; p < 0.01), suggesting fetal brain sparing. Doppler: Normoxic-hypercapnia caused a marked increase in umbilical artery PI (+27.4% ± 7.2; p < 0.001) and a reduction in fetal heart rate (-48 bpm; 95%CI -9.3 to -87.0; p = 0.02), suggesting acute fetal asphyxia.Conclusions: Brief maternal hypercapnic challenge caused BOLD-MRI changes consistent with acute placental and fetal hypoperfusion with fetal brain sparing. The same challenge caused increased umbilical artery PI and fetal bradycardia on Doppler ultrasound, suggestive for acute fetal asphyxia. BOLD-MRI may be a suitable noninvasive imaging strategy to assess placental and fetal organ hemodynamics. [ABSTRACT FROM AUTHOR]

Introduction In spontaneously breathing mice anesthetized with pentobarbital, we observed unexpected paradoxical bradypnea following 5% inhaled CO 2 . Methods Observational study 7–8 week CB6F1/OlaHsd mice ( n = 99), anesthetized with 30 mg/kg intraperitoneal pentobarbital. Interventional study: Adult male Wistar rats ( n = 18), anesthetized either with 30 mg/kg intraperitoneal pentobarbital, 100 mg/kg intraperitoneal ketamine or 1.5% isoflurane. Rats had femoral artery cannulas inserted for hemodynamic monitoring and serial arterial blood gas measurements. Results Observational study: There was a marked reduction in respiratory rate following 4 min of normoxic hypercapnia; average reduction of 9 breaths/min ( p < 0.001) (17% reduction from baseline). Interventional study: increasing CO 2 caused dose-dependent increase in respiratory rate for ketamine–xylazine ( p = 0.007) and isoflurane ( p = 0.016) but dose-dependent decrease in respiratory rate for pentobarbital ( p = 0.046). Increasing inspired CO 2 caused dose-dependent acidosis following pentobarbital and isoflurane ( p = 0.013 and p = 0.017, respectively); but not following ketamine–xylazine ( p = 0.58). Conclusions Inhaled CO 2 caused paradoxical dose-dependent bradypnea in animals anesthetized with pentobarbital, an observation not hitherto reported as a part of anesthesia-related respiratory depression. [ABSTRACT FROM AUTHOR]

AbstractGinosar, Yehuda, Atul Malhotra, and Eli Schwartz. High altitude, continuous positive airway pressure, and obstructive sleep apnea: Subjective observations and objective data. High Alt Med Biol14:186–189, 2013.—We report observations made by one of the authors who ascended to the Thorang La pass (5416 m) in the Nepal Himalaya in October 2010, despite moderate-severe obstructive sleep apnea. We report the first recorded use of nasal CPAP to treat high altitude pulmonary edema (progressively severe dyspnea at rest and severe orthopnea, with tachycardia and tachypnea) that occurred at 4400 meters, when snow and darkness made safe evacuation difficult. We also present objective longitudinal data of the effects of altitude on auto-adjusting CPAP delivered via a portable nasal CPAP device, and on the apnea hypopnea index measured during sleep while using the device. OSA may be a risk factor for the development of high altitude pulmonary edema and we suggest that a nasal CPAP device located in high altitude trekking stations may provide an additional or alternative treatment option for managing high altitude pulmonary edema until evacuation is possible. [ABSTRACT FROM AUTHOR]

Children that undergo treatment for cancer are at risk of suffering from subfertility or hormonal dysfunction due to the detrimental effects of radiotherapy and chemotherapeutic agents on the gonads. Cryopreservation of ovarian tissue prior to treatment offers the possibility of restoring gonadal function after resumption of therapy. Effective counseling and management of pediatric patients is crucial for preserving their future reproductive potential. The purpose of this article is to review recent literature and to revise recommendations we made in a 2007 article. Pediatric hemato-oncology, reproductive endocrinology, surgery, anesthesia and bioethics perspectives are discussed and integrated to propose guidelines for offering ovarian cryopreservation to premenarcheal girls with cancer [ABSTRACT FROM AUTHOR]