Optimal Infusion Rate of Norepinephrine for Prevention of Spinal Hypotension for Cesarean Delivery: A Randomized Controlled Trial, Using Up-Down Sequential Allocation.

BACKGROUND: Norepinephrine has recently been suggested to be as effective as phenylephrine for the prevention of hypotension after spinal anesthesia for cesarean delivery. Moreover, compared to phenylephrine, norepinephrine may be superior in maintaining heart rate (HR) and consequently, cardiac output (CO). A recent study demonstrated that norepinephrine given as a single intravenous bolus is approximately 13 times more potent than phenylephrine. However, it is uncertain whether this finding can be applied when these vasopressors are administered as infusions. Therefore, the optimum infusion rate of norepinephrine remains unknown. We aimed to determine the median effective dose (ED50; defined as the rate of vasopressor infusion required to prevent spinal hypotension in 50% of subjects) of both drugs needed to maintain maternal systolic blood pressure within 20% of the baseline after spinal anesthesia for cesarean delivery and to derive the relative potency ratio. METHODS: Sixty healthy patients undergoing elective cesarean delivery with standardized spinal anesthesia were randomized into 2 groups. The first patient in group 1 received phenylephrine 1200 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (20 µg.min-1). The first patient in group 2 received norepinephrine 96 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (1.6 µg.min-1). Using up-down sequential allocation technique, the vasopressor dose for every subsequent patient was determined by the response in the previous patient. If effective, the next patient received a dose reduced by 150 µg of phenylephrine (2.5 µg.min-1) or 12 µg (0.2 µg.min-1) of norepinephrine. If ineffective, the dose for the next patient was increased by the same amount. The ED50s were determined according to the Dixon-Massey formula. Stroke volume (SV), HR, and CO were also measured. RESULTS: The ED50 was 12.7 µg.min-1 (95% CI, 10.5-14.9) for phenylephrine and 1.01 µg.min-1 (95% CI, 0.84-1.18) for norepinephrine, giving a potency ratio of 12.6 (95% CI, 9.92-15.9). HR, SV, and CO did not differ between the groups. CONCLUSIONS: Norepinephrine is more potent than phenylephrine by a factor of approximately 13 when administered as infusion for equivalent maternal blood pressure control. Based on these findings, we recommend a variable rate prophylactic infusion of norepinephrine to be initiated at 1.9 to 3.8 µg.min-1 for the management of hypotension during cesarean delivery under spinal anesthesia.

Chronic consequences of accidental dural puncture and postdural puncture headache in obstetric anaesthesia - sieving through the evidence.

PURPOSE OF REVIEW: Accidental dural puncture (ADP) and postdural puncture headache (PDPH) are relatively common complications of neuraxial anaesthesia and analgesia in obstetrics. Both may result in acute and chronic morbidity. This review intends to discuss the chronic implications of ADP and PDPH and raise awareness of severe and potentially life-threatening conditions associated with them. RECENT FINDINGS: ADP may be associated with a high rate of PDPH, prolonged hospitalization and increased readmissions. Studies have shown that PDPH may lead to chronic complications such as post-partum depression (PPD), post-traumatic stress disorder (PTSD), chronic headache, backache and reduced breastfeeding rates. There are many case reports indicating that major, severe, life-threatening neurologic complications may follow PDPH in obstetric patients including subdural haematoma and cerebral venous thrombosis. SUMMARY: Many clinicians still believe that ADP and PDPH are benign and self-limiting conditions whereas there may be serious and devastating consequences of both. It is imperative that all women with ADP and PDPH are appropriately diagnosed and treated.

Improving psychological well-being among healthcare workers during the COVID-19 pandemic with an online mindfulness intervention: A randomised waitlist-controlled trial.

The high prevalence of psychological problems observed among healthcare workers (HCWs) during the COVID-19 pandemic called for interventions to safeguard their mental health. We assessed the effectiveness of a 6-week online mindfulness-based intervention in improving well-being and reducing stress among HCWs in Sri Lanka. Eighty HCWs were recruited and randomised into two groups: waitlist-control (WLC) and intervention groups. In the intervention, 1-hour online sessions were conducted at weekly intervals and participants were encouraged to do daily home practice. Stress and well-being were measured pre- and post-intervention using the Perceived Stress Scale and WHO-5 Well-being Index, respectively. One-way analysis of covariance was used to evaluate the effectiveness, in both intention-to-treat (ITT) and complete-case (CC) analyses. A significantly greater improvement in well-being occurred in the intervention arm compared to WLC on both ITT (p = .002) and CC analyses (p < .001), with medium-to-large effect sizes (partial η2 = .117-.278). However, the reduction in stress following the intervention was not significant compared to the WLC group on both ITT (p = .636) and CC analyses (p = .262). In the intervention arm, the median number of sessions attended by participants was 3. Low adherence to the intervention may have contributed to the apparent non-significant effect on stress.

The association between sugar intake during pregnancy and allergies in offspring: a systematic review and a meta-analysis of cohort studies.

CONTEXT: It has been hypothesized that a mother's diet during pregnancy may modulate her offspring's immune system development and lead to development of allergic diseases among offspring. However, the evidence for this is unclear and inconclusive. OBJECTIVE: This systematic review was undertaken to examine the weight of evidence for causality from cohort studies on the association between maternal free sugar intake during pregnancy and development of allergies in offspring. DATA SOURCES: Using a systematic search strategy, PubMed, SCOPUS, and Web of Science databases were searched from inception to May 2020. DATA EXTRACTION: For the reporting of this systematic review, the PRISMA guideline was followed. Studies examining maternal sugar consumption during pregnancy (using self-reported data) and the development of allergic diseases among offspring (infancy to 5 years) were included. DATA ANALYSIS: The Newcastle-Ottawa Scale quality assessment tool was used to assess the study quality. Meta-analysis was conducted using a random-effects model to synthesize the findings. Of 159 publications identified from the search, 5 articles with 4 unique cohort studies were included in this systematic review. The limited meta-analysis showed that a mother's increased free sugar intake during pregnancy was associated with an increased risk of developing asthma in offspring (odds ratio 1.07 [95% CI, 1.00 to 1.14; I2 = 0%]). High free sugar intake by the mother during pregnancy was also associated with increased odds of offspring (to age 7.7 years) developing other common allergies, including allergic rhinitis, atopy and eczema, wheeze, and food allergies . CONCLUSION: From the limited evidence, this review suggests that high free sugar consumption during pregnancy may be associated with the development of allergies in offspring. Clinical guidelines and public health policy recommendations for maternal diet in pregnancy should include advice about reducing free sugar intake due to a possible association with allergies in offspring. However, recommendations should be made with caution considering other maternal and fetal risk factors.

Magnetic resonance imaging of cerebrospinal fluid spread in the epidural space and postdural puncture headache in obstetrics: A proof-of-concept study.

BACKGROUND: Currently, performing an epidural blood patch (EBP) for postdural puncture headache (PDPH) remains a subjective clinical decision. An evidence-based protocol may be of value in identifying women at high risk of developing a severe PDPH. OBJECTIVE: To investigate a potential correlation between the extent of CSF spread in the epidural space, as noted on Magnetic Resonance Imaging (MRI), and the likelihood of development of severe PDPH in obstetric patients. DESIGN: A prospective double-blind quasi-observational study. SETTING: Eight tertiary obstetric units, from NHS hospitals. PATIENTS: Parturients with accidental dural puncture (ADP) underwent T1 and T2-weighted MRI scans of the brain and lumbar spine within 48 h after delivery. All women were followed up, daily, for 1 week. MAIN OUTCOME MEASURES: For each woman, a PDPH severity score was calculated using a four-point Verbal Reporting Scale (none = 0, mild = 1, moderate = 2, severe = 3), with additional points awarded for visual, auditory and emetic symptoms. MRIs were reported by a neuroradiologist, blind to the patient details, using a predefined MRI score. RESULTS: Twenty-two parturients were recruited; 86% (n=19) developed PDPH and 10 of these (53%) required an EBP. The median (range) time for the onset of PDPH was 24 (4 to 126) hours. The median (range) cumulative PDPH severity score was 10 (0 to 21), whereas, the median (range) MRI score was 2.5 (0 to 12). Spearman (rs) analysis identified a significant positive correlation (rs = 0.46; P = 0.024) between cumulative PDPH severity and MRI scores. Of all the radiological features identified in an MRI (lumbar dural shift, caudal brain displacement, epidural or intrathecal blood), the presence of intrathecal blood was most strongly correlated with PDPH severity (P = 0.043). CONCLUSION: Following an ADP, the extent of CSF spread in the epidural space correlates with the severity of subsequent PDPH. CLINICAL TRIAL NUMBER AND REGISTRY URL: ISRCTN14959004, https://www.isrctn.com/.

Management practices for postdural puncture headache in obstetrics: a prospective, international, cohort study.

BACKGROUND: Accidental dural puncture is an uncommon complication of epidural analgesia and can cause postdural puncture headache (PDPH). We aimed to describe management practices and outcomes after PDPH treated by epidural blood patch (EBP) or no EBP. METHODS: Following ethics committee approval, patients who developed PDPH after accidental dural puncture were recruited from participating countries and divided into two groups, those receiving EBP or no EBP. Data registered included patient and procedure characteristics, headache symptoms and intensity, management practices, and complications. Follow-up was at 3 months. RESULTS: A total of 1001 patients from 24 countries were included, of which 647 (64.6%) received an EBP and 354 (35.4%) did not receive an EBP (no-EBP). Higher initial headache intensity was associated with greater use of EBP, odds ratio 1.29 (95% confidence interval 1.19-1.41) per pain intensity unit increase. Headache intensity declined sharply at 4 h after EBP and 127 (19.3%) patients received a second EBP. On average, no or mild headache (numeric rating score≤3) was observed 7 days after diagnosis. Intracranial bleeding was diagnosed in three patients (0.46%), and backache, headache, and analgesic use were more common at 3 months in the EBP group. CONCLUSIONS: Management practices vary between countries, but EBP was more often used in patients with greater initial headache intensity. EBP reduced headache intensity quickly, but about 20% of patients needed a second EBP. After 7 days, most patients had no or mild headache. Backache, headache, and analgesic use were more common at 3 months in patients receiving an EBP.

Neuraxial labor analgesia: a focused narrative review of the 2017 literature.

PURPOSE OF REVIEW: Neuraxial labor analgesia remains the most effective and one of the most commonly utilized methods for pain relief during labor. This narrative review article is a summary of the literature published in 2017 on neuraxial analgesia for labor. RECENT FINDINGS: From a total of 41 identified articles, 13 were included in the review. The topics have been structured into three categories: initiation of neuraxial analgesia, maintenance of neuraxial analgesia, and neuraxial analgesia and obstetric outcomes. Maintenance regimens, such as program intermittent epidural bolus (PIEB) techniques, remain a focus of extensive research with the potential to optimize analgesia for each individual patient. In a similar way, the dural puncture epidural technique could improve the quality of labor analgesia with fewer side effects compared with standard epidural and combined spinal epidural (CSE) techniques. Finally, the increased use of modern technology using portable ultrasound devices with automated imaging software to facilitate epidural catheter placement may offer potential advantages to the obstetric anesthesiologist, especially when dealing with technically difficult cases. SUMMARY: Recent advances, as well as refinements, of current neuraxial analgesia techniques could improve women's experience of labor.

The Society for Obstetric Anesthesia and Perinatology Consensus Statement on the Anesthetic Management of Pregnant and Postpartum Women Receiving Thromboprophylaxis or Higher Dose Anticoagulants.

Venous thromboembolism is recognized as a leading cause of maternal death in the United States. Thromboprophylaxis has been highlighted as a key preventive measure to reduce venous thromboembolism-related maternal deaths. However, the expanded use of thromboprophylaxis in obstetrics will have a major impact on the use and timing of neuraxial analgesia and anesthesia for women undergoing vaginal or cesarean delivery and other obstetric surgeries. Experts from the Society of Obstetric Anesthesia and Perinatology, the American Society of Regional Anesthesia, and hematology have collaborated to develop this comprehensive, pregnancy-specific consensus statement on neuraxial procedures in obstetric patients receiving thromboprophylaxis or higher dose anticoagulants. To date, none of the existing anesthesia societies' recommendations have weighed the potential risks of neuraxial procedures in the presence of thromboprophylaxis, with the competing risks of general anesthesia with a potentially difficult airway, or maternal or fetal harm from avoidance or delayed neuraxial anesthesia. Furthermore, existing guidelines have not integrated the pharmacokinetics and pharmacodynamics of anticoagulants in the obstetric population. The goal of this consensus statement is to provide a practical guide of how to appropriately identify, prepare, and manage pregnant women receiving thromboprophylaxis or higher dose anticoagulants during the ante-, intra-, and postpartum periods. The tactics to facilitate multidisciplinary communication, evidence-based pharmacokinetic and spinal epidural hematoma data, and Decision Aids should help inform risk-benefit discussions with patients and facilitate shared decision making.

Central neuraxial analgesia for labor: an update of the literature.

Numerous techniques are in use to provide analgesia for labor, of which central neuraxial block is widely considered superior to non-neuraxial options. Central neuraxial techniques have evolved over many years to provide greater efficacy, safety and maternal satisfaction. This narrative review focuses on the literature relating to central neuraxial labor analgesia from the past 5 years, from November 2010 to October 2015. We discuss the evidence related to the various central neuraxial techniques used, the increasingly widespread use of ultrasound guidance and the evidence surrounding other novel methods of central neuraxial block insertion. The timing of institution of central neuraxial analgesia in labor is considered, as are the advances in maintenance regimens for labor analgesia.

Parenteral opioid analgesia: Does it still have a role?

Parenteral opioids have been used in labour analgesia for many years, but the ideal opioid in this setting is yet to be found. We review the properties of currently used opioids, their analgesic properties and side effects to mother and foetus. Parenteral opioids can be administered as intermittent boluses or through a patient-controlled intravenous administration system. A wide range of opioid drugs are currently used and provide a variable degree of analgesia. All opioids can cause unwanted maternal side effects such as nausea, vomiting, sedation and respiratory depression. They cross the placenta and have the potential to cause neonatal respiratory depression. Remifentanil patient-controlled intravenous analgesia is becoming increasingly available and popular on some delivery suites. It can provide adequate analgesia and is useful when epidural analgesia is contraindicated. Remifentanil patient-controlled analgesia requires close monitoring in an environment familiar with the technique to avoid maternal hypoxia due to respiratory depression.

Minimum effective fluid volume of colloid to prevent hypotension during caesarean section under spinal anesthesia using a prophylactic phenylephrine infusion: An up-down sequential allocation study.

STUDY OBJECTIVE: The aim of this study was to de termine the minimum effective fluid volume (MEFV) of hydroxyethyl starch 130/0.4 (HES) infused in a preload fashion which would prevent hypotension in 50% of parturients undergoing caesarean section. A secondary objective was to measure the hemodynamic effect of fluid loading on the subjects. DESIGN: This is a prospective, double-blinded, dose-finding study using an up-down sequential allocation design. SETTING: In the operating room. PATIENTS: Thirty healthy parturients undergoing caesarean section under spinal anesthesia using a prophylactic phenylephrine infusion were included in this study. INTERVENTION: The initial HES volume infused in the first patient was 500 mL. A failure of treatment to HES preload was defined as a single episode of systolic hypotension below 20% of baseline value. The next patient in the sequence was given a volume of HES adjusted by either an increment or a decrement of 100 mL according to the previous subject response to fluid preload. MEASUREMENTS: Stroke volume and cardiac output were measured with a bioreactance-based non-invasive cardiac output monitor (NICOM). MAIN RESULTS: The MEFV of HES was 733 mL (95% CI: 388-917 mL). Fluid loading before the administration of the spinal anesthesia resulted in an increase in stroke volume and cardiac output. The combined effect of spinal anesthesia and a phenylephrine infusion reduced the maternal heart rate and cardiac output, but not the stroke volume. CONCLUSION: Our study is the first to investigate variable fluid loading volumes in this population. A HES preload of approximatively 700 mL prevented maternal hypotension in 50% of the parturients under the conditions of this study. We suggest that up-down sequential allocation design is a useful tool to compare different fluid loading regimens in this setting.

Synthesis and characterization of fluorinated azadipyrromethene complexes as acceptors for organic photovoltaics.

Homoleptic zinc(II) complexes of di(phenylacetylene)azadipyrromethene (e.g., Zn(WS3)2) are potential non-fullerene electron acceptors for organic photovoltaics. To tune their properties, fluorination of Zn(WS3)2 at various positions was investigated. Three fluorinated azadipyrromethene-based ligands were synthesized with fluorine at the para-position of the proximal and distal phenyl groups, and at the pyrrolic phenylacetylene moieties. Additionally, a CF3 moiety was added to the pyrrolic phenyl positions to study the effects of a stronger electron withdrawing unit at that position. The four ligands were chelated with zinc(II) and BF2+ and the optical and electrochemical properties were studied. Fluorination had little effect on the optical properties of both the zinc(II) and BF2+ complexes, with λmax in solution around 755 nm and 785 nm, and high molar absorptivities of 100 × 103 M-1cm-1 and 50 × 103 M-1cm-1, respectively. Fluorination of Zn(WS3)2 raised the oxidation potentials by 0.04 V to 0.10 V, and the reduction potentials by 0.01 V to 0.10 V, depending on the position and type of substitution. The largest change was observed for fluorine substitution at the proximal phenyl groups and CF3 substitution at the pyrrolic phenylacetylene moieties. The later complexes are expected to be stronger electron acceptors than Zn(WS3)2, and may enable charge transfer from other conjugated polymer donors that have lower energy levels than poly(3-hexylthiophene) (P3HT).

Inflammation and Epidural-Related Maternal Fever: Proposed Mechanisms.

Intrapartum fever is associated with excessive maternal interventions as well as higher neonatal morbidity. Epidural-related maternal fever (ERMF) contributes to the development of intrapartum fever. The mechanism(s) for ERMF has remained elusive. Here, we consider how inflammatory mechanisms may be modulated by local anesthetic agents and their relevance to ERMF. We also critically reappraise the clinical data with regard to emerging concepts that explain how anesthetic drug-induced metabolic dysfunction, with or without activation of the inflammasome, might trigger the release of nonpathogenic, inflammatory molecules (danger-associated molecular patterns) likely to underlie ERMF.

Side Effects and Efficacy of Neuraxial Opioids in Pregnant Patients at Delivery: A Comprehensive Review.

Neuraxial opioids are an integral part of obstetric anaesthesia and have contributed to greatly improved analgesia for labour and caesarean delivery, both intraoperatively and postoperatively. Despite these advantages, neuraxial opioids may be associated with a number of side effects, some of which (such as respiratory depression), although rare, may be associated with significant morbidity and mortality. The risk of respiratory depression appears to be increased with less lipophilic opioids such as morphine but can be reduced with careful patient selection and monitoring. Other side effects such as pruritus and nausea and vomiting appear to be dose-related and so can be limited by choosing the appropriate dose to optimise analgesia whilst limiting the adverse effects. Urinary retention, the potential neurotoxic effects of neuraxial opioids and the postulated effects on the foetus are also considered but currently it is felt there is not enough evidence to make strong recommendations with regard to specific drugs or dosage. This review aims to discuss the mechanism and incidence of these side effects as well as, where possible, their prevention.

Fibrinogen concentrate versus placebo for treatment of postpartum haemorrhage: study protocol for a randomised controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity. Bleeding is caused by a combination of physical causes, such as failure of the uterus to contract or operations, and is made worse by impairment of the blood clotting system. A number of studies have shown that low levels of the blood clotting factor fibrinogen are associated with progression of bleeding, the need for invasive interventions and transfusions of red blood cells and fresh frozen plasma (FFP). This trial will investigate whether early infusion of fibrinogen concentrate during a major PPH, with the aim of correcting a low fibrinogen to a level that is normal for delivery, based on the Fibtem test, reduces the total number of allogeneic blood products (red blood cells, FFP, cryoprecipitate and platelets) transfused after study medication until discharge, compared to placebo. METHODS/DESIGN: This is a prospective, randomised, double-blind placebo controlled trial. Women will enter an observational phase and if their Fibtem levels fall they will be randomised in the interventional phase. A total of 60 women will be randomised and women are eligible for the trial if they meet all of the following inclusion criteria: age 18 years or over, gestation ≥24 + 0 weeks, haemorrhage of about 1500 ml and on-going bleeding without another complication or haemorrhage of about 1000 ml and caesarean section/uterine atony/placental abruption/placenta praevia/cardiovascular instability or microvascular oozing. Participants with a Fibtem A5 < 16 mm will be randomly allocated to receive either a bolus infusion of fibrinogen concentrate or placebo (isotonic saline). The dose of fibrinogen concentrate or placebo will be calculated based on the woman's ideal body weight for height and the measured Fibtem A5 with the aim of increasing the Fibtem A5 to 23 mm. DISCUSSION: The trial aims to provide evidence on the efficacy and safety of fibrinogen concentrate during acute bleeding in an obstetric setting. TRIAL REGISTRATION: ISRCTN ref: ISRCTN46295339 (01.07.2013); EudraCT: 2012-005511-11 (28.11.2012), UKCRN ref: 13940.

Beyond Fullerenes: Designing Alternative Molecular Electron Acceptors for Solution-Processable Bulk Heterojunction Organic Photovoltaics.

Organic photovoltaics (OPVs) are promising candidates for providing a low cost, widespread energy source by converting sunlight into electricity. Solution-processable active layers have predominantly consisted of a conjugated polymer donor blended with a fullerene derivative as the acceptor. Although fullerene derivatives have been the acceptor of choice, they have drawbacks such as weak visible light absorption and poor energy tuning that limit overall efficiencies. This has recently fueled new research to explore alternative acceptors that would overcome those limitations. During this exploration, one question arises: what are the important design principles for developing nonfullerene acceptors? It is generally accepted that acceptors should have high electron affinity, electron mobility, and absorption coefficient in the visible and near-IR region of the spectra. In this Perspective, we argue that alternative molecular acceptors, when blended with a conjugated polymer donor, should also have large nonplanar structures to promote nanoscale phase separation, charge separation and charge transport in blend films. Additionally, new material design should address the low dielectric constant of organic semiconductors that have so far limited their widespread application.