Method of Anesthesia and Perioperative Risk Factors, Maternal Anesthesia Complications, and Neonatal Mortality Following Cesarean Delivery in Africa: A Substudy of a 7-Day Prospective Observational Cohort Study.

BACKGROUND: The African Surgical Outcomes Study (ASOS) found that maternal mortality following cesarean delivery in Africa is 50 times higher than in high-income countries, and associated with obstetric hemorrhage and anesthesia complications. Mothers who died were more likely to receive general anesthesia (GA). The associations between GA versus spinal anesthesia (SA) and preoperative risk factors, maternal anesthesia complications, and neonatal outcomes following cesarean delivery in Africa are unknown. METHODS: This is a secondary explanatory analysis of 3792 patients undergoing cesarean delivery in ASOS, a prospective observational cohort study, across 22 African countries. The primary aim was to estimate the association between preoperative risk factors and the outcome of the method of anesthesia delivered. Secondary aims were to estimate the association between the method of anesthesia and the outcomes (1) maternal intraoperative hypotension, (2) severe maternal anesthesia complications, and (3) neonatal mortality. Generalized linear mixed models adjusting for obstetric gravidity and gestation, American Society of Anesthesiologists (ASA) category, urgency of surgery, maternal comorbidities, fetal distress, and level of anesthesia provider were used. RESULTS: Of 3709 patients, SA was performed in 2968 (80%) and GA in 741 (20%). Preoperative factors independently associated with GA for cesarean delivery were gestational age (adjusted odds ratio [aOR], 1.093; 95% confidence interval [CI], 1.052-1.135), ASA categories III (aOR, 11.84; 95% CI, 2.93-46.31) and IV (aOR, 11.48; 95% CI, 2.93-44.93), eclampsia (aOR, 3.92; 95% CI, 2.18-7.06), placental abruption (aOR, 6.23; 95% CI, 3.36-11.54), and ruptured uterus (aOR, 3.61; 95% CI, 1.36-9.63). SA was administered to 48 of 94 (51.1%) patients with eclampsia, 12 of 28 (42.9%) with cardiac disease, 14 of 19 (73.7%) with preoperative sepsis, 48 of 76 (63.2%) with antepartum hemorrhage, 30 of 55 (54.5%) with placenta previa, 33 of 78 (42.3%) with placental abruption, and 12 of 29 (41.4%) with a ruptured uterus. The composite maternal outcome "all anesthesia complications" was more frequent in GA than SA (9/741 [1.2%] vs 3/2968 [0.1%], P < .001). The unadjusted neonatal mortality was higher with GA than SA (65/662 [9.8%] vs 73/2669 [2.7%], P < .001). The adjusted analyses demonstrated no association between method of anesthesia and (1) intraoperative maternal hypotension and (2) neonatal mortality. CONCLUSIONS: Analysis of patients undergoing anesthesia for cesarean delivery in Africa indicated patients more likely to receive GA. Anesthesia complications and neonatal mortality were more frequent following GA. SA was often administered to high-risk patients, including those with eclampsia or obstetric hemorrhage. Training in the principles of selection of method of anesthesia, and the skills of safe GA and neonatal resuscitation, is recommended.

Investigation of the Optimum Baseline Blood Pressure for Spinal Anesthesia to Guide Vasopressor Management for Elective Cesarean Delivery: A Case-Control Design.

BACKGROUND: Current guidelines recommend prophylactic vasopressor administration during spinal anesthesia for cesarean delivery to maintain intraoperative blood pressure above 90% of the baseline value. We sought to determine the optimum baseline mean arterial pressure (MAP) reading to guide the management of spinal hypotension. METHODS: We performed a secondary analysis of data collected from normotensive patients presenting for elective cesarean delivery in a tertiary care institution from October 2018 to August 2020. We compared the magnitude of hypotension in patients who reported nausea versus those who did not, using a case-control design. Baseline MAPs at last office visit, morning of surgery, or operating room (pre-spinal) were determined. We calculated the duration and degree of hypotension using the area under the curve (AUC) when the MAP of the respective patient was below 90% of each baseline. RESULTS: The patients who experienced nausea (n=45) had longer and more profound periods of hypotension than those who did not develop nausea (n=240). A comparison of AUC using MAP baseline at the last office visit or on the morning of surgery showed a statistically significant between-group difference, P=0.02, and P=0.005, respectively, and no significant between-group difference when 90% of the MAP baseline in the operating room was used. CONCLUSIONS: Patients had the highest preoperative MAP in the operating room and the AUC was similar for those with and without nausea when the pre-spinal MAP baseline was used. Therefore, maintaining higher intraoperative blood pressure using individual pre-spinal MAP as baseline should reduce intraoperative maternal nausea.

General Anesthesia for Cesarean Delivery for Thrombocytopenia in Hypertensive Disorders of Pregnancy: Findings From the Obstetric Airway Management Registry.

BACKGROUND: In resource-limited environments, spinal anesthesia (SA) is preferred for cesarean delivery. In women at risk of spinal epidural hematoma, particularly those with hypertensive disorders of pregnancy, thrombocytopenia should be excluded before neuraxial blockade. In the context of emergency surgery for fetal distress, this investigation may be hampered by laboratory services being unavailable or off-site. METHODS: The Obstetric Airway Management Registry (ObAMR) is currently active across all anesthesia training institutions affiliated with the University of Cape Town. This multicenter observational study aimed to estimate the proportion of patients receiving general anesthesia (GA) for either confirmed or suspected thrombocytopenia, which was not excluded due to unavailability of laboratory results. To establish the number of GA uses that may have been avoided if platelet counts were available, we retrospectively searched for subsequent platelet counts in patients for whom thrombocytopenia was suspected. An algorithm was proposed, including a simple decision aid for estimating risk versus benefit of SA versus GA, to be followed in the setting of hypertensive disorders of pregnancy and thrombocytopenia. RESULTS: Thrombocytopenia was the indication for GA in 100 of 591 patients (16.9%) captured in the registry. In total, 48 of 591 (8.1%) had confirmed thrombocytopenia, and 52 of 591 (8.8%) had suspected thrombocytopenia. Of these patients, 91 of 100 had a hypertensive disorder of pregnancy. In the confirmed thrombocytopenia group, the indication for GA was a platelet count <75 × 10 9 /L. In the suspected thrombocytopenia group, 46 of 52 (88.5%) platelet counts could be retrospectively traced. The median (interquartile range) platelet count was 178 × 10 9 /L (93 - 233 × 10 9 /L), and platelets exceeded 75 × 10 9 /L in 41 of 46 patients (89.1%). In the 5 of 46 patients with retrospectively confirmed thrombocytopenia, 2 had hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, 2 had antepartum hemorrhage with preeclampsia, and 1 had isolated thrombocytopenia with preeclampsia. CONCLUSIONS: In 17% of patients, the indication for GA was thrombocytopenia. Of these, 52 of 100, or nearly 9% of the total of 591, received GA because a platelet count was unavailable at the time of surgery. The importance of early laboratory assessment, when available, should be emphasized. Overall, 41 of 591 (6.9%) had a platelet count >75 × 10 9 /L and would not have needed GA if their platelet count had been known. After following the constructed algorithm and applying the decision aid to assess risk and benefit, there may be circumstances in which the clinician justifiably opts for SA when a platelet count is indicated but unavailable.

Spinal hypotension in obstetrics: Context-sensitive prevention and management.

Spinal hypotension during caesarean section remains a common complication, with important attendant maternal and fetal adverse outcomes. Research elucidating the mechanisms of spinal hypotension has led to the development and refinement of effective management strategies, with a particular emphasis on prophylactic vasopressor administration. This has proved effective in well-resourced settings, with maternal comfort and the elimination of nausea now considered the primary aim of treatment. In resource-limited settings, sophisticated strategies are not feasible due to insufficient equipment, staff, and expertise. Therefore, in these areas spinal hypotension remains an important cause of maternal and fetal morbidity and mortality. Translational, context-sensitive research in resource-limited settings has shown promise in implementing pragmatic strategies based on research from resource-rich environments. We review the current best practice for the prevention and treatment of spinal hypotension, with a special emphasis on effective strategies in resource-limited settings. We further suggest a research agenda to address the knowledge gap in specific contexts.

Preeclampsia in 2021-a Perioperative Medical Challenge for the Anesthesiologist.

The authors provide a review of recent advances in the understanding of pathophysiology and perioperative management of preeclampsia and eclampsia, from the perspective of the anesthesiologist. This review includes aspects of assessment of severity of disease, hemodynamic monitoring, peripartum anesthesia care, and postpartum management. The perioperative management of patients with eclampsia is also discussed.

A Multicenter, Cross-Sectional Quality Improvement Project: The Perioperative Implementation of a Hypertension Protocol by Anesthesiologists.

BACKGROUND: Hypertension is a common risk factor for cardiovascular morbidity and mortality, with a high prevalence in patients presenting for elective surgery. In limited resource environments, patients have poor access to primary care physicians, limiting the efficacy of lifestyle modification for the management of hypertension. In these circumstances, the perioperative period presents a unique opportunity for diagnosis and initiation and/or modification of pharmacotherapy of hypertension. Anesthesiologists are ideally placed to lead this aspect of perioperative medicine. The study objective was for anesthesiologists to identify patients at the preoperative visit with previously undiagnosed or poorly controlled chronic hypertension and follow a simple management algorithm. METHODS: In collaboration with expert physicians, we designed and implemented an algorithm for the diagnosis and management of chronic hypertension. This was a multicenter, cross-sectional quality improvement project in 7 hospitals in the Western Cape, South Africa. On the day before scheduled elective surgery, adult in-patients had 2 sets of blood pressure (BP) readings taken, one by nurses and the other by anesthesiologists, using a noninvasive automated BP device. These were averaged on an electronic database, to diagnose hypertension. Patients with normal BP or well-controlled hypertension required no further management. Those with borderline BP received educational pamphlets. Patients with stage 1 or 2 hypertension were managed with medication according to the algorithm, starting 1 day postoperatively, and provided with educational pamphlets. Patients with stage 3 disease had their surgery postponed and were referred to a physician. The primary outcome was adherence by the anesthesiologist to the algorithm in the diagnosis and management of hypertension. An 80% adherence rate was considered successful implementation. The secondary outcome was the adherence to the algorithm at discharge. RESULTS: Two hundred ninety-eight patients were screened for hypertension. One hundred six patients were eligible for the quality improvement project. Thirty-seven (34.9%) had borderline BP readings, 43 (40.6%) had stage 1, 22 (20.8%) stage 2, and 4 (3.8%) stage 3 hypertension, respectively. The adherence rate by the anesthesiologist in initiating treatment according to the algorithm was 89 of 106 (84.0%; 95% confidence interval [CI, 77.0-91.0). There was full adherence to the algorithm in 59 of 106 (55.5%; 95% CI, 46.2-65.1) at the time of discharge from hospital. CONCLUSIONS: Anesthesiologists successfully implemented a quality improvement project for diagnosis and management of hypertension in the perioperative period. This has the potential to reduce the public health burden of hypertension in limited resource environments. Successful ongoing prescription and follow-up requires cooperation within a multidisciplinary team.

Mechanism of Iminium Salt-Catalyzed C(sp3)-H Amination: Factors Controlling Hydride Transfer versus H-Atom Abstraction.

Carbon-nitrogen bonds are extremely prevalent in pharmaceuticals, natural products, and other biologically relevant molecules such as nucleic acids and proteins. Intermolecular amination of C(sp3)-H bonds by catalytic nitrene transfer is a promising method for forging C-N bonds. An organocatalytic approach to nitrene transfer by way of an iminium salt offers a site-selective method for C(sp3)-H amination. Understanding of this amination mechanism including the nature of the relevant intermediates and the factors controlling the mechanism of the N-H bond formation step would aid in the design of catalysts and C(sp3)-H amination methods. In this work, the mechanism of the iminium salt-catalyzed C(sp3)-H amination via nitrene transfer was elucidated computationally using quantum mechanical methods and molecular dynamics simulations. Dispersion-corrected density functional theory (DFT) calculations provide support for an open singlet biradical species in equilibrium with the lower energy triplet species. Calculations further reveal that while the singlet biradical species undergoes N-H bond formation by a hydride transfer process, the triplet species forms the N-H bond by H-atom abstraction. Molecular dynamics (MD) simulations rule out the possibility of a fast rebound of the carbon substrate following N-H bond formation. A predictive model for mode of activation and site-selectivity that is consistent with experimental observations is presented.

Anesthesia for Urgent Cesarean Section.

Cesarean section (CS) is a common surgical procedure worldwide. The anesthesiologist is responsible, together with obstetrician and neonatologist, for safe perioperative management. A continuum of risk exists for urgent CS. The decision-to-delivery interval is an important audit tool, to ensure international standards are upheld and good outcomes for mother and neonate are achieved. Urgent CS may be performed under either GA or RA, with benefits and risks attributable to each. Specific clinical scenarios require an individualized approach to anesthesia, including hemorrhage, hypertensive disorders, cardiac disease, the difficult airway and fetal compromise. Ongoing training is integral to the provision of safe anesthesia.

Overcoming Language Barriers Using an Information Video on Spinal Anesthesia for Cesarean Delivery: Implementation and Impact on Maternal Anxiety.

BACKGROUND: It is unknown whether the implementation of an information video on spinal anesthesia for cesarean delivery, narrated in a patient's first language, reduces anxiety, increases satisfaction, and improves doctor-patient communication if there is a language barrier. In South Africa, most doctors speak English, and patients speak Xhosa, with educational and cultural disparities existing in many doctor-patient interactions. METHODS: One hundred seventy-five Xhosa patients scheduled for elective cesarean delivery were enrolled in the study. The first 92 patients received "usual care" verbal explanations of the spinal anesthesia procedure (control group); the next 83 patients watched a spinal anesthesia information video (intervention group), narrated in Xhosa. Videos were displayed using smartphones. Maternal anxiety was assessed before and after spinal explanation, using a Numerical Visual Analog Anxiety Scale (NVAAS). A difference in postexplanation NVAAS score of 1.5 points between intervention and control groups was regarded as clinically significant. Patient satisfaction was assessed using the Maternal Satisfaction Scale for Cesarean Section (MSSCS). RESULTS: The mean (standard deviation [SD]) age (31.5 years [5.2 years] and 32.1 years [5.4 years]) and preexplanation NVAAS score (4.2 [3.2] and 4.0 [3.0]) of the intervention and control groups, respectively, showed no difference at baseline. The mean (SD) postexplanation decrease in NVAAS score was greater in the intervention than in the control group (1.6 [3.5] vs 0.7 [2.3]; P = .046; unadjusted mean difference, 0.9 points [95% confidence interval {CI}, 0.02-1.8]). A linear regression model for the postexplanation NVAAS score showed that the intervention effect was significantly associated with the preexplanation score (P = .002), adjusted for age and English fluency. Patients with preexplanation NVAAS scores ≥5 showed a statistically significant intervention effect. There was no significant difference in patient satisfaction between the intervention and control groups. The smartphone was an accessible and convenient display medium for the video. Ninety-nine percent of patients exposed to the intervention would recommend watching the video before the procedure. CONCLUSIONS: In this pilot study, lower NVAAS scores were observed in anxious patients, when a Xhosa information video was used to ameliorate challenges posed by a doctor-patient language barrier. It is easily implemented and demonstrates a novel use of mobile health technology. The study provides baseline data to inform sample size calculations for future studies. A high level of patient recommendation for the video suggests that this is an agreeable practice.

Point-of-Care Ultrasound Abnormalities in Late-Onset Severe Preeclampsia: Prevalence and Association With Serum Albumin and Brain Natriuretic Peptide.

BACKGROUND: Pilot studies applying point-of-care ultrasound (POCUS) in preeclampsia indicate the presence of pulmonary interstitial edema, cerebral edema, and cardiac dysfunction. Laboratory markers of oncotic pressure (albumin) and cardiac dysfunction (brain natriuretic peptide [BNP]) may be abnormal, but the clinical application remains unclear. We investigated the prevalence of pulmonary interstitial syndrome (PIS), cardiac dysfunction, and increased optic nerve sheath diameter (ONSD) in late-onset preeclampsia with severe features. The primary aim was to examine the association between PIS or ONSD and maternal serum albumin level. The secondary aims were to explore the association between cardiac dysfunction and PIS, ONSD, BNP, and serum albumin level and between POCUS-derived parameters and a suspicious or pathological cardiotocograph. METHODS: Ninety-five women were enrolled in this prospective observational cohort study. A POCUS examination of lungs, heart, and ONSD was performed. PIS was defined as a bilateral B-line pattern on lung ultrasound and diastolic dysfunction according to an algorithm of the American Society of Echocardiography. ONSD >5.8 mm was interpreted as compatible with raised intracranial pressure (>20 mm Hg). Serum BNP and albumin levels were also measured. RESULTS: PIS, diastolic dysfunction, systolic dysfunction, and raised left ventricular end-diastolic pressure (LVEDP) were present in 23 (24%), 31 (33%), 9 (10%), and 20 (25%) women, respectively. ONSD was increased in 27 (28%) women. Concerning the primary outcome, there was no association between albumin level and PIS (P = .4) or ONSD (P = .63). With respect to secondary outcomes, there was no association between albumin level and systolic dysfunction (P = .21) or raised LVEDP (P = .44). PIS was associated with diastolic dysfunction (P = .02) and raised LVEDP (P = .009; negative predictive value, 85%). BNP level was associated with systolic (P < .001) and diastolic dysfunction (P = .003) and LVEDP (P = .007). No association was found between POCUS abnormalities and a suspicious/pathological cardiotocograph (P = .07). CONCLUSIONS: PIS, diastolic dysfunction, and increased ONSD were common in preeclampsia with severe features. Cardiac ultrasound abnormalities may be more useful than albumin levels in predicting PIS. The absence of PIS may exclude raised LVEDP. The further clinical relevance of PIS and raised ONSD remains to be established. BNP level was associated with cardiac ultrasound abnormalities. Although this study was not designed to directly influence clinical management, the findings suggest that POCUS may serve as a useful adjunct to clinical examination for the obstetric anesthesiologist managing these complex patients.

Maternal and neonatal outcomes after caesarean delivery in the African Surgical Outcomes Study: a 7-day prospective observational cohort study.

BACKGROUND: Maternal and neonatal mortality is high in Africa, but few large, prospective studies have been done to investigate the risk factors associated with these poor maternal and neonatal outcomes. METHODS: A 7-day, international, prospective, observational cohort study was done in patients having caesarean delivery in 183 hospitals across 22 countries in Africa. The inclusion criteria were all consecutive patients (aged ≥18 years) admitted to participating centres having elective and non-elective caesarean delivery during the 7-day study cohort period. To ensure a representative sample, each hospital had to provide data for 90% of the eligible patients during the recruitment week. The primary outcome was in-hospital maternal mortality and complications, which were assessed by local investigators. The study was registered on the South African National Health Research Database, number KZ_2015RP7_22, and on ClinicalTrials.gov, number NCT03044899. FINDINGS: Between February, 2016, and May, 2016, 3792 patients were recruited from hospitals across Africa. 3685 were included in the postoperative complications analysis (107 missing data) and 3684 were included in the maternal mortality analysis (108 missing data). These hospitals had a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0·7 per 100 000 population (IQR 0·2-2·0). Maternal mortality was 20 (0·5%) of 3684 patients (95% CI 0·3-0·8). Complications occurred in 633 (17·4%) of 3636 mothers (16·2-18·6), which were predominantly severe intraoperative and postoperative bleeding (136 [3·8%] of 3612 mothers). Maternal mortality was independently associated with a preoperative presentation of placenta praevia, placental abruption, ruptured uterus, antepartum haemorrhage (odds ratio 4·47 [95% CI 1·46-13·65]), and perioperative severe obstetric haemorrhage (5·87 [1·99-17·34]) or anaesthesia complications (11·47 (1·20-109·20]). Neonatal mortality was 153 (4·4%) of 3506 infants (95% CI 3·7-5·0). INTERPRETATION: Maternal mortality after caesarean delivery in Africa is 50 times higher than that of high-income countries and is driven by peripartum haemorrhage and anaesthesia complications. Neonatal mortality is double the global average. Early identification and appropriate management of mothers at risk of peripartum haemorrhage might improve maternal and neonatal outcomes in Africa. FUNDING: Medical Research Council of South Africa.

Cardiac Structure and Function in Morbidly Obese Parturients: An Echocardiographic Study.

BACKGROUND: The increasing prevalence of obesity worldwide is a major threat to global health. Cardiac structural and functional changes are well documented for obesity as well as for pregnancy, but there is limited literature on morbidly obese parturients. We hypothesized that there are both cardiac structural and functional differences between morbidly obese pregnant women and pregnant women of normal body mass index (BMI). METHODS: This prospective cross-sectional study was performed in 2 referral maternity units in Cape Town, South Africa, over a 3-month period. Forty morbidly obese pregnant women of BMI ≥40 kg·m (group O) were compared to 45 pregnant women of BMI ≤30 kg·m (group N). Cardiac structure and function were assessed by transthoracic echocardiography, according to the recommendations of the British Society of Echocardiography. The 2-sample t-test with unequal variances was used for the comparison of the mean values between the groups. RESULTS: Acceptable echocardiographic images were obtained in all obese women. Statistical significance was defined as P < .0225 after applying the Benjamini-Hochberg correction for multiple testing. Mean (standard deviation) mean arterial pressure was higher in group O (91 [8.42] vs 84 [9.49] mm Hg, P < .001). There were no between-group differences in heart rate, stroke volume, or cardiac index (84 [12] vs 79 [13] beats·minute, P = .103; 64.4 [9.7] vs 59.5 [13.5] mL, P = .069; 2551 [474] vs 2729 [623] mL·minute·m, P = .156, for groups O and N, respectively). Stroke volume index was lower, and left ventricular mass was higher in group O (30.14 [4.51] vs 34.25 [7.00] mL·m, P = .003; 152 [24] vs 115 [29] g, P < .001). S' septal was lower in group O (8.43 [1.20] vs 9.25 [1.64] cm·second, P = .012). Considering diastolic function, isovolumetric relaxation time was significantly prolonged in group O (73 [15] vs 61 [15] milliseconds, P < .001). The septal tissue Doppler index E' septal was lower in group O (9.08 [1.69] vs 11.28 [3.18], P < .001). There were no between-group differences in E' average (10.7 [2.3] vs 12.0 [2.7], P = .018, O versus N) or E/E' average (7.85 [1.77] vs 7.27 [1.68], P = .137, O versus N). Right ventricular E'/A' was lower in group O (1.07 [0.47] vs 1.29 [0.32], P = .016). CONCLUSIONS: Cardiac index did not differ between obese pregnant women and those with normal BMI. Their increased left ventricular mass and lower stroke volume index could indicate a limited adaptive reserve. Obese women had minor decreases in septal left ventricular tissue Doppler velocity, but the E/E' average values did not suggest clinically significant diastolic dysfunction.

Resting Hemodynamics and Response to Exercise Using the 6-Minute Walk Test in Late Pregnancy: An International Prospective Multicentre Study.

BACKGROUND: Cardiac disease is the leading cause of maternal death. Assessment of cardiovascular fitness is important in pregnant women because it is linked to increased risk of cardiac disease but is rarely undertaken or studied. The 6-Minute Walk Test (6MWT) is a safe exercise test but is not used in pregnancy. We determined the 95% reference interval for resting heart rate (HR) and distance walked for the 6MWT, as well as hemodynamic recovery variables, and quantified expectations and actual experiences of exertion and breathlessness with exercise in late pregnancy. METHODS: After institutional research board approval (Australian and New Zealand Clinical Trials Registry Number: 12615000964516), 300 healthy term nulliparous pregnant women performed the 6MWT at 3 tertiary referral obstetric hospitals using a standardized protocol. Each woman underwent two 6MWT with maximum 15-minute recovery period after each test. Hemodynamic variables were measured at rest and after exercise. Participants were asked 4 questions, 2 regarding expectation and 2 regarding actual experience, using the Rating of Perceived Exertion scale and Modified Borg Dyspnea scale. RESULTS: Participant characteristics and resting variables were mean (standard deviation [SD]); age, 31 years (4.2 years); body mass index, 27 kg/m (2.9 kg/m); gestational age, 37 weeks (1.3 weeks); HR, 85 bpm (10.8 bpm) with 95% reference interval 64-106 bpm; systolic blood pressure, 112 mm Hg (10.2 mm Hg); diastolic blood pressure, 72 mm Hg (8.6 mm Hg); oxygen saturation, 98% (0.9%); and respiratory rate, 18 breaths/min (5.7 breaths/min). The mean (SD) average distance walked was 488 m (94.9 m) with a speed of 3.0 mph (0.64 mph) with a 95% reference interval of 302-674 m. The mean (SD) HR increase with exercise was 12 bpm (11.0 bpm) with a median [quartile] recovery time of 5.0 minutes [1-8 minutes]. A lower resting HR was associated with increased distance walked (r = -0.207; 95% confidence interval, -0.313 to -0.096; P < .001). A greater HR change with exercise was associated with increased recovery time from exercise (r = 0.736; 95% confidence interval, 0.697-0.784; P < .001). Sixty-three percent and 83% of participants, respectively, expected to be more exerted and breathless than they actually were with exercise. CONCLUSIONS: The 6MWT is feasible and applicable in term pregnant women. The reference intervals for resting HR and distance walked in the 6MWT have been generated. HR increases by approximately 12 bpm with submaximal exercise, and half of the women recovered within 5 minutes of submaximal exercise. Women expected to be more exerted and breathless than they actually were with exercise.

Selective Heteroaryl N-Oxidation of Amine-Containing Molecules.

The first examples of nonenzymatic N-oxidation of heteroarenes in the presence of amines are reported. Pyridine, quinoline, and isoquinoline N-oxides are selectively formed in the presence of more reactive aliphatic and alicyclic amines by use of an in situ protonation strategy and an iminium salt organocatalyst. Application to late-stage functionalization that mimics phase 1 metabolism of small-molecule drugs is also demonstrated.

Core Temperature Monitoring in Obstetric Spinal Anesthesia Using an Ingestible Telemetric Sensor.

BACKGROUND: Perioperative hypothermia may affect maternal and neonatal outcomes after obstetric spinal anesthesia. Core temperature is often poorly monitored during spinal anesthesia, due to the lack of an accurate noninvasive core temperature monitor. The aim of this study was to describe core temperature changes and temperature recovery during spinal anesthesia for elective cesarean delivery. We expected that obstetric spinal anesthesia would be associated with a clinically relevant thermoregulatory insult (core temperature decrease >1.0°C). METHODS: A descriptive study was conducted in 28 women. An ingestible telemetric temperature sensor was used to record core temperature over time (measured every 10 seconds). The primary outcome was the maximum core temperature decrease after spinal anesthetic injection. The secondary outcomes were lowest absolute core temperature, time to lowest temperature, time to recovery of core temperature, hypothermic exposure (degree-hours below 37.0°C), and the time-weighted hypothermic exposure (median number of degrees below 37.0°C per hour). Basic descriptive statistics, median spline smooth, and integration of the area below the 37.0°C line of the temperature-over-time curve were utilized to analyze the data. RESULTS: Intestinal temperature decreased by a mean (standard deviation) of 1.30°C (0.31); 99% confidence interval (CI), 1.14 to 1.46 after spinal anesthetic injection. The median (interquartile range [IQR]) time to temperature nadir was 0.96 (0.73-1.32) hours (95% CI, 0.88-1.22). Fourteen of the 28 participants experienced intestinal temperatures below 36.0°C after spinal injection. Temperature was monitored for a minimum of 8 hours after spinal injection. In 8 of 28 participants, intestinal temperature did not recover to baseline during the monitored period. A median (IQR) of 4.59 (3.38-5.92) hours (95% CI, 3.45-5.90) was required for recovery to baseline intestinal temperature in the remaining 20 patients. Participants experienced a median (IQR) of 1.97 (1.00-2.68) degree-hours of hypothermic exposure (95% CI, 1.23-2.45). The median (IQR) number of degrees below 37.0°C per hour was 0.45 (0.35-0.60) (95% CI, 0.36-0.58). CONCLUSIONS: During cesarean delivery under spinal anesthesia, women experienced a rapid decrease in core temperature. Using an intestinal telemetric sensor, the perioperative thermal insult and recovery were documented with high resolution. Fifty percent of participants in this study became hypothermic. Although the surgical procedure is typically of short duration, women undergoing spinal anesthesia for cesarean delivery experience significant hypothermic exposure and compromised thermoregulation for several hours.

The Effect of Prophylactic Phenylephrine and Ephedrine Infusions on Umbilical Artery Blood pH in Women With Preeclampsia Undergoing Cesarean Delivery With Spinal Anesthesia: A Randomized, Double-Blind Trial.

BACKGROUND: Spinal anesthesia for cesarean delivery is associated with a high incidence of hypotension. Phenylephrine results in higher umbilical artery pH than ephedrine when used to prevent or treat hypotension in healthy women. We hypothesized that phenylephrine compared to ephedrine would result in higher umbilical artery pH in women with preeclampsia undergoing cesarean delivery with spinal anesthesia. METHODS: This study was a randomized double-blind clinical trial. Nonlaboring women with preeclampsia scheduled for cesarean delivery with spinal anesthesia at Prentice Women's Hospital of Northwestern Medicine were randomized to receive prophylactic infusions of phenylephrine or ephedrine titrated to maintain systolic blood pressure >80% of baseline. Spinal anesthesia consisted of hyperbaric 0.75% bupivacaine 12 mg, fentanyl 15 µg, and morphine 150 µg. The primary outcome was umbilical arterial blood pH and the secondary outcome was umbilical artery base excess. RESULTS: One hundred ten women were enrolled in the study and 54 per group were included in the analysis. There were 74 and 72 infants delivered in the ephedrine and phenylephrine groups, respectively. The phenylephrine:ephedrine ratio for umbilical artery pH was 1.002 (95% confidence interval [CI], 0.997-1.007). Mean [standard deviation] umbilical artery pH was not different between the ephedrine 7.20 [0.10] and phenylephrine 7.22 [0.07] groups (mean difference -0.02, 95% CI of the difference -0.06 to 0.07; P = .38). Median (first, third quartiles) umbilical artery base excess was -3.4 mEq/L (-5.7 to -2.0 mEq/L) in the ephedrine group and -2.8 mEq/L (-4.6 to -2.2mEq/L) in the phenylephrine group (difference -0.6 mEq/L, 95% CI of the difference -1.6 to 0.3 mEq/L; P = .10). When adjusted for gestational age and infant gender, umbilical artery pH did not differ between groups. There were also no differences in the umbilical artery pH stratified by magnesium therapy or by the severity of preeclampsia. CONCLUSIONS: We were unable to demonstrate a beneficial effect of phenylephrine on umbilical artery pH compared with ephedrine. Our findings suggest that phenylephrine may not have a clinically important advantage compared with ephedrine with regard to improved neonatal acid-base status when used to prevent spinal anesthesia-induced hypotension in women with preeclampsia undergoing cesarean delivery.