Epidural analgesia and neonatal short-term outcomes during routine childbirth: a 10-year retrospective analysis from the national birth registry of Austria.

BACKGROUND: Epidural analgesia (EA) is well-accepted for pain relief during labor. Still, the impact on neonatal short-term outcome is under continuous debate. This study assessed the outcome of neonates in deliveries with and without EA in a nationwide cohort. METHODS: We analyzed the National Birth Registry of Austria between 2008 and 2017 of primiparous women with vaginal birth of singleton pregnancies. Neonatal short-term morbidity was assessed by arterial cord pH and base excess (BE). Secondary outcomes were admission to a neonatological intensive care unit, APGAR scores, and perinatal mortality. Propensity score-adjusted regression models were used to investigate the association of EA with short-term neonatal outcome. RESULTS: Of 247,536 included deliveries, 52 153 received EA (21%). Differences in pH (7.24 vs. 7.25; 97.5% CI -0.0066 to -0.0047) and BE (-5.89±3.2 vs. -6.15±3.2 mmol/L; 97.5% CI 0.32 to 0.40) with EA could be shown. APGAR score at five minutes <7 was more frequent with EA (OR 1.45; 95% CI: 1.29 to 1.63). Admission to a neonatological intensive care unit occurred more often with EA (4.7% vs. 3.4%) with an OR for EA of 1.2 (95% CI: 1.14 to 1.26). EA was not associated with perinatal mortality (OR 1.33; 95% CI: 0.79 to 2.25). CONCLUSIONS: EA showed no clinically relevant association with neonatal short-term outcome. Higher rates of NICU admission and APGAR score after five minutes <7 were observed with EA. The overall use of EA in Austria is low, and an investigation of causes may be indicated.

Role of mitochondrial DNA level in epidural-related maternal fever: a single-centre, observational, pilot study.

INTRODUCTION: Epidural analgesia has been associated with intrapartum maternal fever development. Epidural-related maternal fever (ERMF) is believed to be based on a non-infectious inflammatory reaction. Circulating cell-free mitochondrial deoxyribonucleic acid (mtDNA) is one of the possible triggers of sterile inflammatory processes; however, a connection has not been investigated so far. Therefore, this study aimed to investigate cell-free mtDNA alterations in women in labour with ERMF in comparison with non-febrile women. MATERIAL AND METHODS: A total of 60 women in labour were assessed for maternal temperature every 4 h and blood samples were obtained at the beginning and after delivery. Depending on the analgesia and the development of fever (axillary temperature ≥ 37.5 °C), the women were allocated either to the group of no epidural analgesia (n = 17), to epidural analgesia no fever (n = 34) or to ERMF (n = 9). Circulating cell-free mtDNA was analysed in the maternal plasma for the primary outcome whereas secondary outcomes include the evaluation of inflammatory cytokine release, as well as placental inflammatory signs. RESULTS: Of the women with epidural analgesia, 20% (n = 9) developed ERMF and demonstrated a decrease of circulating mtDNA levels during labour (p = 0.04), but a trend towards higher free nuclear DNA. Furthermore, women with maternal pyrexia showed a 1.5 fold increased level of Interleukin-6 during labour. A correlation was found between premature rupture of membranes and ERMF. CONCLUSIONS: The pilot trial revealed an evident obstetric anaesthesia phenomenon of maternal fever due to epidural analgesia in 20% of women in labour, demonstrating counterregulated free mtDNA and nDNA. Further work is urgently required to understand the connections between the ERMF occurrence and circulating cell-free mtDNA as a potential source of sterile inflammation. TRIAL REGISTRATION: NCT0405223 on clinicaltrials.gov (registered on 25/07/2019).

The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma.

The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia.

[Infection prevention in the operating theater: practice-oriented recommendations for anesthesiologists]. / Infektionsprävention im OP: praxisorientierte Empfehlungen für AnästhesistInnen.

This article is intended to provide clinically working anesthesiologists with a practice-oriented overview of selected important current guidelines and recommendations pertaining to intraoperative prevention of infection. The contents of this article are based on the guidelines or recommendation of the World Health Organization (WHO) and the Association of the Scientific Medical Societies in Germany (AWMF) as well as the Commission for Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute (RKI). The authors' objective is to foster and support the standard of infection prevention and control in the operating theater by optimizing the standard of hygiene in daily practice to reduce the number of perioperative infections.

Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium.

Patients presenting with insufficient tissue oxygenation and impaired lung function as in acute respiratory distress syndrome (ARDS) frequently require mechanical ventilation with supplemental oxygen. Despite the lung being used to experiencing the highest partial pressure of oxygen during healthy breathing, the organ is susceptible to oxygen-induced injury at supraphysiological concentrations. Hyperoxia-induced lung injury (HALI) has been regarded as a second hit to pre-existing lung injury and ventilator-induced lung injury (VILI) attributed to oxidative stress. The injured lung has a tendency to form atelectasis, a cyclic collapse and reopening of alveoli. The affected lung areas experience oxygen conditions that oscillate between hyperoxia and hypoxia rather than remaining in a constant hyperoxic state. Mechanisms of HALI have been investigated in many animal models previously. These studies provided insights into the effects of hyperoxia on the whole organism. However, cell type-specific responses have not been dissected in detail, but are necessary for a complete mechanistic understanding of ongoing pathological processes. In our study, we investigated the effects of constant and intermittent hyperoxia on the lung endothelium from a mouse by an in vitro proteomic approach. We demonstrate that these oxygen conditions have characteristic effects on the pulmonary endothelial proteome that underlie the physiological (patho)mechanisms.

Oxygen-Dependent Changes in the N-Glycome of Murine Pulmonary Endothelial Cells.

Supplemental oxygen is frequently used together with mechanical ventilation to achieve sufficient blood oxygenation. Despite the undoubted benefits, it is vigorously debated whether too much oxygen can also have unpredicted side-effects. Uncertainty is also due to the fact that the molecular mechanisms are still insufficiently understood. The lung endothelium is covered with an exceptionally broad glycocalyx, carrying N- and O-glycans, proteoglycans, glycolipids and glycosaminoglycans. Glycan structures are not genetically determined but depend on the metabolic state and the expression level and activity of biosynthetic and glycan remodeling enzymes, which can be influenced by oxygen and the redox status of the cell. Altered glycan structures can affect cell interactions and signaling. In this study, we investigated the effect of different oxygen conditions on aspects of the glycobiology of the pulmonary endothelium with an emphasis on N-glycans and terminal sialylation using an in vitro cell culture system. We combined a proteomic approach with N-glycan structure analysis by LC-MS, qRT-PCR, sialic acid analysis and lectin binding to show that constant and intermittent hyperoxia induced time dependent changes in global and surface glycosylation. An siRNA approach identified St6gal1 as being primarily responsible for the early transient increase of α2-6 sialylated structures in response to hyperoxia.

Cerebral microemboli during extracorporeal life support: a single-centre cohort study.

OBJECTIVES: The aim of this study was to investigate the load and composition of cerebral microemboli in adult patients undergoing venoarterial extracorporeal life support (ECLS). METHODS: Adult ECLS patients were investigated for the presence of cerebral microemboli and compared to critically ill, pressure-controlled ventilated controls and healthy volunteers. Cerebral microemboli were detected in both middle cerebral arteries for 30 min using transcranial Doppler ultrasound. Neurological outcome (ischaemic stroke, global brain ischaemia, intracerebral haemorrhage, seizure, metabolic encephalopathy, sensorimotor sequelae and neuropsychiatric disorders) was additionally evaluated. RESULTS: Twenty ECLS patients (cannulations: 15 femoro-femoral, 4 femoro-subclavian, 1 femoro-aortic), 20 critically ill controls and 20 healthy volunteers were analysed. ECLS patients had statistically significantly more cerebral microemboli than critically ill controls {123 (43-547) [median (interquartile range)] vs 35 (16-74), difference: 88 [95% confidence interval (CI) 19-320], P = 0.023} and healthy volunteers [11 (5-12), difference: 112 (95% CI 45-351), P < 0.0001]. In ECLS patients, 96.5% (7346/7613) of cerebral microemboli were of gaseous composition, while solid cerebral microemboli [1 (0-5)] were detected in 12 out of 20 patients. ECLS patients had more neurological complications than critically ill controls (12/20 vs 3/20, P = 0.003). In ECLS patients, a high microembolic rate (>100/30 min) tended to be associated with neurological complications including ischaemic stroke, neuropsychiatric disorders, sensorimotor sequelae and non-convulsive status epilepticus (odds ratio 4.5, 95% CI 0.46-66.62; P = 0.559). CONCLUSIONS: Our results indicate that adult ECLS patients are continuously exposed to many gaseous and, frequently, to few solid cerebral microemboli. Prolonged cerebral microemboli formation may contribute to neurological morbidity related to ECLS treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02020759, https://clinicaltrials.gov/ct2/show/NCT02020759?term=erdoes&rank=1.

[Neuraxial Morphine for Postoperative Analgesia after Caesarean Deliveries]. / Neuroaxiale Gabe von Morphin nach Sectio caesarea: ein Update.

The use of neuraxial morphine, in combination with nonopioid analgesic regimens for postoperative analgesia after Caesarean deliveries is common practice, especially in the Anglo-American world. Neuraxial morphine offers a longer-lasting superior analgesia than intravenous opioids or patient-controlled analgesia. If neuraxial anaesthesia is being used for a caesarean delivery, it may be recommended to concomitantly administer neuraxial morphine for the postoperative analgesia.A low dose of neuraxial morphine in a healthy parturient bears a low morbidity and mortality risk. The optimal frequency, duration and modality of respiratory monitoring for patients at low risk for respiratory depression is dependent on the dose of morphine administered and the patient-specific and obstetric risk profile.

Brief High Oxygen Concentration Induces Oxidative Stress in Leukocytes and Platelets: A Randomized Cross-over Pilot Study in Healthy Male Volunteers.

BACKGROUND: Supplemental oxygen is administered routinely in the clinical setting to relieve or prevent tissue hypoxia, but excessive exposure may induce oxidative damage or disrupt essential homeostatic functions. It is speculated that oxidative stress in leukocytes and platelets may contribute to vascular diseases by promoting inflammation and cell aggregation. METHODS: In this pilot study 30 healthy male volunteers (18-65 years) were exposed to high oxygen concentration (non-rebreather mask, 8 L/min, 100% O2) and synthetic air (non-rebreather mask, 8 L/min, 21% O2) in a cross-over design for 20 min at a 3-week interval. Venous blood samples were obtained at baseline and 1, 3, and 6 h postintervention. Primary outcome was generation of reactive oxygen species in leukocytes as measured by the redox-sensitive fluorescent dye dihydrorhodamine 123. Additional outcomes were oxidative stress in platelets and platelet aggregation as measured by thromboelastography (ROTEM) and Multiplate analyses. FINDINGS: High oxygen exposure induced oxidative stress in leukocytes as evidenced by significantly higher mean fluorescence intensity (MFI) compared with synthetic air at 3 h postintervention (47% higher, P = 0.015) and 6 h postintervention (37% higher, P = 0.133). Oxidative stress was also detectable in platelets (33% higher MFI in comparison with synthetic air at 6 h, P = 0.024; MFI 20% above baseline at 3 h, P  = 0.036; 37% above baseline at 6 h, P = 0.002). ROTEM analyses demonstrated reduced mean clotting time 1 h postintervention compared with baseline (-4%, P = 0.049), whereas there were no significant effects on other surrogate coagulation parameters. CONCLUSION: Clinically relevant oxygen exposure induces oxidative stress in leukocytes and platelets, which may influence the immune and clotting functions of these cells.

Oxygen conditions oscillating between hypoxia and hyperoxia induce different effects in the pulmonary endothelium compared to constant oxygen conditions.

The pulmonary endothelium is an immediate recipient of high oxygen concentrations upon oxygen therapy and mediates down-stream responses. Cyclic collapse and reopening of atelectatic lung areas during mechanical ventilation with high fractions of inspired oxygen result in the propagation of oxygen oscillations in the hypoxic/hyperoxic range. We used primary murine lung endothelial cell cultures to investigate cell responses to constant and oscillating oxygen conditions in the hypoxic to hyperoxic range. Severe constant hyperoxia had pro-inflammatory and cytotoxic effects including an increase in expression of ICAM1, E-selectin, and RAGE at 24 hr exposure. The coagulative/fibrinolytic system responded by upregulation of uPA, tPA, and vWF and PAI1 under constant severe hyperoxia. Among antioxidant enzymes, the upregulation of SOD2, TXN1, TXNRD3, GPX1, and Gstp1 at 24 hr, but downregulation of SOD3 at 72 hr constant hyperoxia was evident. Hypoxic/hyperoxic oscillating oxygen conditions induced pro-inflammatory cytokine release to a lesser extent and later than constant hyperoxia. Gene expression analyses showed upregulation of NFKB p65 mRNA at 72 hr. More evident was a biphasic response of NOS3 and ACE1 gene expression (downregulation until 24 hr and upregulation at 72 hr). ACE2 mRNA was upregulated until 72 hr, but shedding of the mature protein from the cell surface favored ACE1. Oscillations resulted in severe production of peroxynitrite, but apart from upregulation of Gstp1 at 24 hr responses of antioxidative proteins were less pronounced than under constant hyperoxia. Oscillating oxygen in the hypoxic/hyperoxic range has a characteristical impact on vasoactive mediators like NOS3 and on the activation of the renin-angiotensin system in the lung endothelium.

Understanding Cellular Redox Homeostasis: A Challenge for Precision Medicine.

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term "oxidative stress" is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.

Investigating Disturbances of Oxygen Homeostasis: From Cellular Mechanisms to the Clinical Practice.

Soon after its discovery in the 18th century, oxygen was applied as a therapeutic agent to treat severely ill patients. Lack of oxygen, commonly termed as hypoxia, is frequently encountered in different disease states and is detrimental to human life. However, at the end of the 19th century, Paul Bert and James Lorrain Smith identified what is known as oxygen toxicity. The molecular basis of this phenomenon is oxygen's readiness to accept electrons and to form different variants of aggressive radicals that interfere with normal cell functions. The human body has evolved to maintain oxygen homeostasis by different molecular systems that are either activated in the case of oxygen under-supply, or to scavenge and to transform oxygen radicals when excess amounts are encountered. Research has provided insights into cellular mechanisms of oxygen homeostasis and is still called upon in order to better understand related diseases. Oxygen therapy is one of the prime clinical interventions, as it is life saving, readily available, easy to apply and economically affordable. However, the current state of research also implicates a reconsidering of the liberal application of oxygen causing hyperoxia. Increasing evidence from preclinical and clinical studies suggest detrimental outcomes as a consequence of liberal oxygen therapy. In this review, we summarize concepts of cellular mechanisms regarding different forms of disturbed cellular oxygen homeostasis that may help to better define safe clinical application of oxygen therapy.

Ropivacaine Activates Multiple Proapoptotic and Inflammatory Signaling Pathways That Might Subsume to Trigger Epidural-Related Maternal Fever.

BACKGROUND: Epidural-related maternal fever (ERMF) is an adverse effect of epidural analgesia during labor and is associated with perinatal and neonatal morbidity. Local anesthetics have been proposed to trigger ERMF via sterile inflammation. Ropivacaine is currently the most frequently used epidural anesthetic and considered least toxic. This study investigates molecular effects of ropivacaine on human umbilical vein endothelial cells (HUVECs) as model system for endothelial cells and human placental trophoblasts (TBs), compares the effects to the putative anti-inflammatory lidocaine and investigates the partially alleviating impact of the anti-inflammatory corticosteroid dexamethasone. METHODS: HUVECs and TBs were exposed to ropivacaine (35 µM-7 mM) or lidocaine (21 mM) with or without dexamethasone (1 µM). AnnexinV/propidium iodide staining and lactate dehydrogenase release were used to analyze apoptosis and cytotoxicity. Proinflammatory interleukins-6 (IL-6) and IL-8 as well as prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA), while activation of signaling pathways was detected by Western blotting. Oxidative stress was visualized by live cell imaging and quantification of antioxidant proteins, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, platelet endothelial cell adhesion molecule 1, cyclooxygenase 2, and mitochondrial deoxyribonucleic acid by real-time polymerase chain reaction. Dissipation of the mitochondrial membrane potential was assessed with cytofluorimetric analysis using the J-Aggregate (JC-1 staining [cytofluorimetric analysis using the J-Aggregate]). RESULTS: Ropivacaine exposure dose-dependently induced apoptosis and an increased release of IL-6, IL-8, and PGE2 from HUVECs and TBs. Furthermore, caspase-3, nuclear factor-κB, and p38 mitogen-activated protein kinase pathways were activated, while extracellular signal-regulated kinase 1/2 and protein kinase B (Akt) were dephosphorylated. Downregulation of antioxidative proteins induced oxidative stress and upregulation of ICAM1, VCAM1, and PECAM1 possibly facilitate leukocyte transmigration. Mitochondrial effects included increased release of the proinflammatory mitochondrial DNA damage-associated molecular patterns, but no significant dissipation of the mitochondrial membrane potential. Conversely, lidocaine exhibited repression of IL-6 and IL-8 release over all time points, and early downregulation of COX2 and cell adhesion molecules, which was followed by a late overshooting reaction. Dexamethasone reduced especially inflammatory effects, but as an inducer of mitophagy, had negative long-term effects on mitochondrial function. CONCLUSIONS: This study suggests that ropivacaine causes cellular injury and death in HUVECs and TBs via different signaling pathways. The detrimental effects induced by ropivacaine are only partially blunted by dexamethasone. This observation strengthens the importance of inflammation in ERMF.

Epigenetic modulation of tenascin C in the heart: implications on myocardial ischemia, hypertrophy and metabolism.

BACKGROUND: Tenascin C (TN-C) is considered to play a pathophysiological role in maladaptive left ventricular remodeling. Yet, the mechanism underlying TN-C-dependent cardiac dysfunction remains elusive. METHOD: The present study was designed to investigate the effect of hypoxia and hypertrophic stimuli on TN-C expression in H9c2 cells and its putative regulation by epigenetic mechanisms, namely DNA promoter methylation and microRNAs. In addition, rats subjected to myocardial infarction (MI) were investigated. H9c2 cells were subjected to oxygen and glucose deprivation; incubated with angiotensin II (Ang II); or human TN-C (hTN-C) purified protein. Hypertrophic and fibrotic markers, TN-C promoter methylation as well as mir-335 expression were assessed by reverse transcription and quantitative polymerase chain reaction while TN-C protein levels were assessed by ELISA. RESULTS: Tn-C mRNA expression was markedly increased by both oxygen and glucose deprivation and Ang II (P < 0.01, respectively). In addition, Ang-II-dependent TN-C upregulation was explained by reduced promoter methylation (P < 0.05). Cells treated with hTN-C displayed upregulation of Bnp, Mmp2, ß-Mhc, integrin α6 and integrin ß1. Furthermore, hTN-C treated cells showed a significant reduction in adenosine monophosphate and adenosine triphosphate levels. In vivo, plasma and myocardial TN-C levels were increased 7 days post MI (P < 0.05, respectively). This increment in TN-C was accompanied by upregulation of mir-335 (P < 0.01). In conclusion, both hypoxic and hypertrophic stimuli lead to epigenetically driven TN-C upregulation and subsequent impairment of cellular energy metabolism in cardiomyoblasts. CONCLUSION: These findings might enlighten our understanding on maladaptive left ventricular remodeling and direct towards a strong involvement of TN-C.

PO2 oscillations induce lung injury and inflammation.

BACKGROUND: Mechanical ventilation can lead to ventilator-induced lung injury (VILI). In addition to the well-known mechanical forces of volutrauma, barotrauma, and atelectrauma, non-mechanical mechanisms have recently been discussed as contributing to the pathogenesis of VILI. One such mechanism is oscillations in partial pressure of oxygen (PO2) which originate in lung tissue in the presence of within-breath recruitment and derecruitment of alveoli. The purpose of this study was to investigate this mechanism's possible independent effects on lung tissue and inflammation in a porcine model. METHODS: To separately study the impact of PO2 oscillations on the lungs, an in vivo model was set up that allowed for generating mixed-venous PO2 oscillations by the use of veno-venous extracorporeal membrane oxygenation (vvECMO) in a state of minimal mechanical stress. While applying the identical minimal-invasive ventilator settings, 16 healthy female piglets (weight 50 ± 4 kg) were either exposed for 6 h to a constant mixed-venous hemoglobin saturation (SmvO2) of 65% (which equals a PmvO2 of 41 Torr) (control group), or an oscillating SmvO2 (intervention group) of 40-90% (which equals PmvO2 oscillations of 30-68 Torr)-while systemic normoxia in both groups was maintained. The primary endpoint of histologic lung damage was assessed by ex vivo histologic lung injury scoring (LIS), the secondary endpoint of pulmonary inflammation by qRT-PCR of lung tissue. Cytokine concentration of plasma was carried out by ELISA. A bioinformatic microarray analysis of lung samples was performed to generate hypotheses about underlying pathomechanisms. RESULTS: The LIS showed significantly more severe damage of lung tissue after exposure to PO2 oscillations compared to controls (0.53 [0.51; 0.58] vs. 0.27 [0.23; 0.28]; P = 0.0025). Likewise, a higher expression of TNF-α (P = 0.0127), IL-1ß (P = 0.0013), IL-6 (P = 0.0007), and iNOS (P = 0.0013) in lung tissue was determined after exposure to PO2 oscillations. Cytokines in plasma showed a similar trend between the groups, however, without significant differences. Results of the microarray analysis suggest that inflammatory (IL-6) and oxidative stress (NO/ROS) signaling pathways are involved in the pathology linked to PO2 oscillations. CONCLUSIONS: Artificial mixed-venous PO2 oscillations induced lung damage and pulmonary inflammation in healthy animals during lung protective ventilation. These findings suggest that PO2 oscillations represent an independent mechanism of VILI.

[Which medications are safe while breastfeeding? : A synopsis for the anesthetist, obstetrician and pediatrician]. / Welche Medikamente sind in der Stillzeit erlaubt? : Eine Übersicht für den Anästhesisten, Geburtshelfer und Kinderarzt.

Pharmacokinetic data on drug administration during lactation are often inconsistent or missing. For legal reasons medicinal drug product information generally advises to interrupt breastfeeding for 24 h after medication intake. However this is not standard of care in clinical practice as the mother should be instructed to initiate breastfeeding as soon as possible after giving birth. At the same time the medication exposure over the breast milk for the newborn should be minimized. Aim of this article is to summarize pharmacokinetic data and to give important clinical information on medications frequently administered during the lactation period. As a general rule a mother can start breastfeeding following anesthesia as soon as she is able to get her baby latched on her breast.

Impact of CPAP on Forehead Near-infrared Spectroscopy Measurements in Patients With Acute Respiratory Failure: Truth or Illusion.

BACKGROUND: Critically ill patients with acute respiratory failure admitted to an intensive care unit are at high risk for cerebral hypoxia. We investigated the impact of continuous positive airway pressure (CPAP) therapy on regional cerebral tissue oxygenation (rSO2). MATERIALS AND METHODS: In total, 40 extubated surgical intensive care unit patients requiring classic oxygen therapy (COT) for acute respiratory failure were examined. Near-infrared spectroscopy (INVOS 5100C, Covidien) was used for 30 minutes to detect bilateral rSO2 during COT via facemask (6 L/min) and CPAP therapy (40% fraction of inspired oxygen, 8 cm H2O CPAP) using a randomized crossover study design. Patients served as their own control. Continuous hemodynamic routine monitoring and blood gas analysis were performed. The effect of CPAP therapy on rSO2 and influence of assessed covariables were investigated using a mixed linear model. RESULTS: Median rSO2 increased from 57.9% (95% confidence interval [CI], 54.2-61.5) during COT to 62.8% (95% CI, 59.2-66.5) during CPAP therapy (P<0.0001). The estimated difference from the mixed model between COT and CPAP is -5.0 (95% CI, -6.3 to -3.7). Median arterial partial pressure of carbon dioxide decreased from 47.8±5.1 mm Hg during COT to 43.1±5 mm Hg during CPAP (P<0.001), whereas arterial partial pressure of oxygen remained unchanged (P=0.329). In total, 23% of patients had SO2 levels <50%, with a higher prevalence under COT. CONCLUSIONS: Our results reveal that CPAP therapy compared with COT may influence rSO2 in patients with acute respiratory failure. However, the cause of the rSO2 increase following CPAP application remains to be elucidated, and the accuracy of cerebral oximetry during CPAP therapy in patients with acute respiratory failure remains questionable.

Intermittent Hypoxia Activates Duration-Dependent Protective and Injurious Mechanisms in Mouse Lung Endothelial Cells.

Intermittent hypoxia is a major factor in clinical conditions like the obstructive sleep apnea syndrome or the cyclic recruitment and derecruitment of atelectasis in acute respiratory distress syndrome and positive pressure mechanical ventilation. In vivo investigations of the direct impact of intermittent hypoxia are frequently hampered by multiple co-morbidities of patients. Therefore, cell culture experiments are important model systems to elucidate molecular mechanisms that are involved in the cellular response to alternating oxygen conditions and could represent future targets for tailored therapies. In this study, we focused on mouse lung endothelial cells as a first frontier to encounter altered oxygen due to disturbances in airway or lung function, that play an important role in the development of secondary diseases like vascular disease and pulmonary hypertension. We analyzed key markers for endothelial function including cell adhesion molecules, molecules involved in regulation of fibrinolysis, hemostasis, redox balance, and regulators of gene expression like miRNAs. Results show that short-time exposure to intermittent hypoxia has little impact on vitality and health of cells. At early timepoints and up to 24 h, many endothelial markers are unchanged in their expression and some indicators of injury are even downregulated. However, in the long-term, multiple signaling pathways are activated, that ultimately result in cellular inflammation, oxidative stress, and apoptosis.

Maternal serum mitochondrial DNA (mtDNA) levels are elevated in preeclampsia - A matched case-control study.

OBJECTIVE: Oxidative stress and mitochondrial dysfunction may play a crucial role in preeclampsia (PE). The aim of this study was to investigate differences in maternal levels of serum-mitochondrial (mt) DNA, a proposed biomarker for mitochondrial dysfunction, in women with PE compared to healthy pregnant women. STUDY DESIGN: Using samples obtained from the prospective Biobank study, we measured serum-mtDNA levels in pregnant women diagnosed with PE and in women with uneventful pregnancies, matched for gestational and maternal age, BMI, and smoking status. In a second step, we performed a generalized linear model to detect associations between mtDNA-serum-levels and certain conditions during pregnancy. RESULTS: Mean mtDNA levels were significantly higher in PE (n = 20) than in matched controls (n = 20) and were 0.00767 (SD 0.00255) U/L and 0.00513 (SD 0.00458) U/L, respectively (p = 0.038). We did not find a significant correlation between higher mtDNA levels and early onset PE, IUGR, maternal age, or maternal BMI. Interestingly, increased mtDNA levels were significantly associated with female fetal sex (p = 0.003). CONCLUSION: Our findings strengthen the hypothesis postulating that oxidative stress and mitochondrial dysfunction are key factors in the pathophysiology of PE. More prospective studies are highly warranted to further investigate the role of mtDNA in PE and assess the usefulness as a possible biomarker for PE.