Epidural-related maternal fever: incidence, pathophysiology, outcomes, and management.

Epidural-related maternal fever affects 15% to 25% of patients who receive a labor epidural. Two meta-analyses demonstrated that epidural-related maternal fever is a clinical phenomenon, which is unlikely to be caused by selection bias. All commonly used neuraxial techniques, local anesthetics with or without opioids, and maintenance regimens are associated with epidural-related maternal fever, however, the impact of each component is unknown. Two major theories surrounding epidural-related maternal fever development have been proposed. First, labor epidural analgesia may lead to the development of hyperthermia through a sterile (noninfectious) inflammatory process. This process may involve reduced activation of caspase-1 (a protease involved in cell apoptosis and activation of proinflammatory pathways) secondary to bupivacaine, which impairs the release of the antipyrogenic cytokine, interleukin-1-receptor antagonist, from circulating leucocytes. Detailed mechanistic processes of epidural-related maternal fever remain to be determined. Second, thermoregulatory mechanisms secondary to neuraxial blockade have been proposed, which may also contribute to epidural-related maternal fever development. Currently, there is no prophylactic strategy that can safely prevent epidural-related maternal fever from occurring nor can it easily be distinguished clinically from other causes of intrapartum fever, such as chorioamnionitis. Because intrapartum fever (of any etiology) is associated with adverse outcomes for both the mother and baby, it is important that all parturients who develop intrapartum fever are investigated and treated appropriately, irrespective of labor epidural utilization. Institution of treatment with appropriate antimicrobial therapy is recommended if an infectious cause of fever is suspected. There is currently insufficient evidence to warrant a change in recommendations regarding provision of labor epidural analgesia and the benefits of good quality labor analgesia must continue to be reiterated to expectant mothers.

Osteopontin mediates necroptosis in lung injury after transplantation of ischaemic renal allografts in rats.

BACKGROUND: Respiratory complications after surgery are associated with morbidity and mortality. Acute lung injury can result from the systemic inflammatory response after acute kidney injury. The mechanisms behind this remote injury are not fully understood. In this study, a renal transplantation model was used to investigate remote lung injury and the underlying molecular mechanisms, especially the role of osteopontin (OPN). METHODS: In vitro, human lung epithelial cell line (A549) and monocyte/macrophage cell line (U937) were challenged with tumour necrosis factor-alpha (TNF-α) in combination with OPN. In vivo, the Fischer rat renal grafts were extracted and stored in 4°C University of Wisconsin preserving solution for up to 16 h, and transplanted into Lewis rat recipients. Lungs were harvested on Day 1 after grafting for further analysis. RESULTS: Renal engraftment was associated with pathological changes and an increase in TNF-α and interleukin-1 beta in the lung of the recipient. OPN, endoplasmic reticulum (ER) stress, and necroptosis were increased in both the recipient lung and A549 cells challenged with TNF-α. Exogenous OPN exacerbated lung injury and necroptosis. Suppression of OPN through siRNA reduced remote lung injury by mitigation of ER stress, necroptosis, and the inflammatory response. CONCLUSIONS: Renal allograft transplant triggers recipient remote lung injury, which is, in part, mediated by OPN signalling. This study may provide a molecular basis for strategies to be developed to treat such perioperative complications.

Measuring enhanced recovery in obstetrics: a narrative review.

Enhanced recovery after cesarean delivery is a protocolized approach to perioperative care, with the aim to optimize maternal recovery after surgery. It is associated with improved maternal and neonatal outcomes, including decreased length of hospital stay, opioid consumption, pain scores, complications, increased maternal satisfaction, and increased breastfeeding success. However, the pace and enthusiasm of adoption of enhanced recovery after cesarean delivery internationally has not yet been matched with high-quality evidence demonstrating its benefit, and current studies provide low- to very low-quality evidence in support of enhanced recovery after cesarean delivery. This article provides a summary of current measures of enhanced recovery after cesarean delivery success, and optimal measures of inpatient and outpatient postpartum recovery. We summarize outcomes from 22 published enhanced recovery after cesarean delivery implementation studies and 2 meta-analyses. A variety of disparate metrics have been used to measure enhanced recovery after cesarean delivery success, including process measures (length of hospital stay, bundle compliance, preoperative fasting time, time to first mobilization, time to urinary catheter removal), maternal outcomes (patient-reported outcome measures, complications, opioid consumption, satisfaction), neonatal outcomes (breastfeeding success, Apgar scores, maternal-neonatal bonding), cost savings, and complication rates (maternal readmission rate, urinary recatheterization rate, neonatal readmission rate). A core outcome set for use in enhanced recovery after cesarean delivery studies has been developed through Delphi consensus, involving stakeholders including obstetricians, anesthesiologists, patients, and a midwife. Fifteen measures covering key aspects of enhanced recovery after cesarean delivery adoption are recommended for use in future enhanced recovery after cesarean delivery implementation studies. The use of these outcome measures could improve the quality of evidence surrounding enhanced recovery after cesarean delivery. Using evidence-based evaluation guidelines developed by the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) group, the Obstetric Quality of Recovery score (ObsQoR) was identified as the best patient-reported outcome measure for inpatient postpartum recovery. Advances in our understanding of postpartum recovery as a multidimensional and dynamic construct have opened new avenues for the identification of optimum patient-reported outcome measures in this context. The use of standardized measures such as these will facilitate pooling of data in future studies and improve overall levels of evidence surrounding enhanced recovery after cesarean delivery. Larger studies with optimal study designs, using recommended outcomes including patient-reported outcome measures, will reduce variation and improve data quality to help guide future recommendations.

Evaluation of Domains of Patient-Reported Outcome Measures for Recovery After Childbirth: A Scoping and Systematic Review.

Importance: Despite the global delivery rate being approximately 259 deliveries per minute in 2018, postpartum recovery remains poorly defined. Objectives: To identify validated patient-reported outcome measures (PROMs) used to assess outpatient and inpatient postpartum recovery, evaluate frequency of PROM use, report the proportion of identified PROMs used within each recovery domain, report the number of published studies within each recovery domain, summarize descriptive data (country of origin, year of study, and journal specialty) for published studies using PROMs to evaluate postpartum recovery, and report PROMs used to evaluate global postpartum recovery. Evidence Review: This study followed PRISMA-ScR guidelines. A literature search of 4 databases (MEDLINE through PubMed, Embase, Web of Science, and CINAHL) was performed on July 1, 2019, to identify PROMs used to evaluate 12 author-defined domains of postpartum recovery. All psychometrically evaluated PROMs used to evaluate inpatient or outpatient postpartum recovery after all delivery modes were included. Findings: From 8008 screened titles and abstracts, 573 studies (515 outpatient and 58 inpatient) were identified in this review. A total of 201 PROMs were used to assess recovery for outpatient studies and 73 PROMs were used to assess recovery for inpatient studies. The top 5 domains (with highest to lowest numbers of PROMs) used to assess outpatient recovery were psychosocial distress (77 PROMs), surgical complications (26 PROMs), psychosocial support (27 PROMs), motherhood experience (16 PROMs), and sexual function (13 PROMs). Among inpatient studies, the top 5 domains were psychosocial distress (32 PROMs), motherhood experience (7 PROMs), psychosocial support (5 PROMs), fatigue (5 PROMs), and cognition (3 PROMs). The 3 most frequently used PROMs were the Edinburgh Postnatal Depression Scale (267 studies), Short-Form 36 Health Questionnaire (global recovery assessment; 40 studies), and Female Sexual Function Index (35 studies). A total of 24 global recovery PROMs were identified among all included studies. Most studies were undertaken in the United States within the last decade and were published in psychiatry and obstetrics and gynecology journals. Conclusions and Relevance: Most PROMs identified in this review evaluated a single domain of recovery. Future research should focus on determining the psychometric properties of individual and global recovery PROMs identified in this review to provide recommendations regarding optimum measures of postpartum recovery.

Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like 2.

Perinatal hypoxic ischaemic encephalopathy (HIE) has a high mortality rate with neuropsychological impairment. This study investigated the neuroprotective effects of argon against neonatal hypoxic-ischaemic brain injury.In vitro cortical neuronal cell cultures derived from rat foetuses were subjected to an oxygen and glucose deprivation (OGD) challenge for 90 minutes and then exposed to 70% argon or nitrogen with 5% carbon dioxide and balanced with oxygen for 2 hours.In vivo, seven-day-old rats were subjected to unilateral common carotid artery ligation followed by hypoxic (8% oxygen balanced with nitrogen) insult for 90 minutes. They were exposed to 70% argon or nitrogen balanced with oxygen for 2 hours. In vitro, argon treatment of cortical neuronal cultures resulted in a significant increase of p-mTOR and Nuclear factor (erythroid-derived 2)-like 2(Nrf2) and protection against OGD challenge. Inhibition of m-TOR through Rapamycin or Nrf2 through siRNA abolished argon-mediated cyto-protection. In vivo, argon exposure significantly enhanced Nrf2 and its down-stream effector NAD(P)H Dehydrogenase, Quinone 1(NQO1) and superoxide dismutase 1(SOD1). Oxidative stress, neuroinflammation and neuronal cell death were significantly decreased and brain infarction was markedly reduced. Blocking PI-3K through wortmannin or ERK1/2 through U0126 attenuated argon-mediated neuroprotection.These data provide a new molecular mechanism for the potential application of Argon as a neuroprotectant in HIE.

Lipid emulsion for local anesthetic systemic toxicity.

The accidental overdose of local anesthetics may prove fatal. The commonly used amide local anesthetics have varying adverse effects on the myocardium, and beyond a certain dose all are capable of causing death. Local anesthetics are the most frequently used drugs amongst anesthetists and although uncommon, local anaesthetic systemic toxicity accounts for a high proportion of mortality, with local anaesthetic-induced cardiac arrest particularly resistant to standard resuscitation methods. Over the last decade, there has been convincing evidence of intravenous lipid emulsions as a rescue in local anesthetic-cardiotoxicity, and anesthetic organisations, over the globe have developed guidelines on the use of this drug. Despite this, awareness amongst practitioners appears to be lacking. All who use local anesthetics in their practice should have an appreciation of patients at high risk of toxicity, early symptoms and signs of toxicity, preventative measures when using local anesthetics, and the initial management of systemic toxicity with intravenous lipid emulsion. In this paper we intend to discuss the pharmacology and pathophysiology of local anesthetics and toxicity, and the rationale for lipid emulsion therapy.