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).

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.

[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.

[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.

Inhaled AP301 for treatment of pulmonary edema in mechanically ventilated patients with acute respiratory distress syndrome: a phase IIa randomized placebo-controlled trial.

BACKGROUND: High-permeability pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS) and is frequently accompanied by impaired alveolar fluid clearance (AFC). AP301 enhances AFC by activating epithelial sodium channels (ENaCs) on alveolar epithelial cells, and we investigated its effect on extravascular lung water index (EVLWI) in mechanically ventilated patients with ARDS. METHODS: Forty adult mechanically ventilated patients with ARDS were included in a randomized, double-blind, placebo-controlled trial for proof of concept. Patients were treated with inhaled AP301 (n = 20) or placebo (0.9% NaCl; n = 20) twice daily for 7 days. EVLWI was measured by thermodilution (PiCCO®), and treatment groups were compared using the nonparametric Mann-Whitney U test. RESULTS: AP301 inhalation was well tolerated. No differences in mean baseline-adjusted change in EVLWI from screening to day 7 were found between the AP301 and placebo group (p = 0.196). There was no difference in the PaO2/FiO2 ratio, ventilation pressures, Murray lung injury score, or 28-day mortality between the treatment groups. An exploratory subgroup analysis according to severity of illness showed reductions in EVLWI (p = 0.04) and ventilation pressures (p < 0.05) over 7 days in patients with initial sequential organ failure assessment (SOFA) scores ≥11 inhaling AP301 versus placebo, but not in patients with SOFA scores ≤10. CONCLUSIONS: There was no difference in mean baseline-adjusted EVLWI between the AP301 and placebo group. An exploratory post-hoc subgroup analysis indicated reduced EVLWI in patients with SOFA scores ≥11 receiving AP301. These results suggest further confirmation in future clinical trials of inhaled AP301 for treatment of pulmonary edema in patients with ARDS. TRIAL REGISTRATION: The study was prospectively registered at clinicaltrials.gov, NCT01627613 . Registered 20 June 2012.

[Pain therapy during labour]. / Schmerztherapie während der Geburt.

To date the gold standard of treating labour pain is regional analgesia by application of epidural analgesia. When offering epidural analgesia, the programmed intermittent epidural bolus (PIEB) is more effective in terms of pain reduction, less motor blocks and higher satisfaction of the parturient compared to continuous application via perfusor pump. An upcoming alternative to epidural analgesia is remifentanil, a short acting and potent opioid. Remifentanil, however, requires haemodynamic monitoring as cardiac and respiratory impairment has been described. Nitrous oxide has been used for decades in the Anglosphere but it is a greenhouse gas, and interactions with Vitamin B12 are possible. Using novel extraction systems, nitrous oxide has become more attractive for treatment of the initial phase of labour pain in Central Europe. In order to provide the parturient with the best possible and with a tailored pain concept an interdisciplinary approach with obstetricians, midwives and anaesthesiologists is required.

[Recent standards in management of obstetric anesthesia]. / Aktuelle Versorgungskonzepte in der geburtshilflichen Anästhesie.

The following article contains information not only for the clinical working anaesthesiologist, but also for other specialists involved in obstetric affairs. Besides a synopsis of a German translation of the current "Practice Guidelines for Obstetric Anaesthesia 2016" [1], written by the American Society of Anesthesiologists, the authors provide personal information regarding major topics of obstetric anaesthesia including pre-anaesthesia patient evaluation, equipment and staff at the delivery room, use of general anaesthesia, peridural analgesia, spinal anaesthesia, combined spinal-epidural anaesthesia, single shot spinal anaesthesia, and programmed intermittent epidural bolus.

Intermittent Hypoxia Causes Inflammation and Injury to Human Adult Cardiac Myocytes.

BACKGROUND: Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia. METHODS: HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression. RESULTS: In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1ß, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways. CONCLUSIONS: Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia exposure may produce rapid and substantial damage to the human heart.

Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Stress.

BACKGROUND: Oxidative stress is the predominant pathogenic mechanism of ischaemia-reperfusion (IR) injury. The noble gas argon has been shown to alleviate oxidative stress-related myocardial and cerebral injury. The risk of lung IR injury is increased in some major surgeries, reducing clinical outcome. However, no study has examined the lung-protective efficacy of argon preconditioning. The present study investigated the protective effects of argon preconditioning on airway epithelial cells exposed to hydrogen peroxide (H2O2) to induce oxidative stress. METHODS: A549 airway epithelial cells were treated with a cytotoxic concentration of H2O2 after exposure to standard air or 30 or 50% argon/21% oxygen/5% carbon dioxide/rest nitrogen for 30, 45 or 180 min. Cells were stained with annexin V/propidium iodide, and apoptosis was evaluated by fluorescence-activated cell sorting. Protective signalling pathways activated by argon exposure were identified by Western blot analysis for phosphorylated candidate molecules of the mitogen-activated protein kinase and protein kinase B (Akt) pathways. RESULTS: Preconditioning with 50% argon for 30, 45 and 180 min and 30% argon for 180 min caused significant protection of A549 cells against H2O2-induced apoptosis, with increases in cellular viability of 5-47% (p < 0.0001). A small adverse effect was also observed, which presented as a 12-15% increase in cellular necrosis in argon-treated groups. Argon exposure resulted in early activation of c-Jun N-terminal kinase (JNK) and p38, peaking 10- 30 min after the start of preconditioning, and delayed activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, peaking after 60-90 min. CONCLUSIONS: Argon preconditioning protects airway epithelial cells from H2O2-induced apoptotic cell death. Argon activates the JNK, p38, and ERK1/2 pathways, but not the Akt pathway. The cytoprotective properties of argon suggest possible prophylactic applications in surgery-related IR injury of the lungs.

Real-time in-vivo imaging of pulmonary capillary perfusion using probe-based confocal laser scanning endomicroscopy in pigs: An interventional laboratory study.

BACKGROUND: Little is known about real-time in-vivo microscopy of pulmonary capillary perfusion because current microscopy requires direct access to lung tissue with surgical intervention such as the thoracic-window technique and open-lung model. OBJECTIVES: To evaluate if probe-based confocal laser scanning endomicroscopy (pCLE) via the trachea allows for real-time in-vivo visualisation of pulmonary capillary density and red blood cell (RBC) velocity in pigs. DESIGN: An interventional animal study. SETTING: European University Hospital. ANIMALS: Nine female domestic pigs (50 to 60 kg) were used. MAIN OUTCOME MEASURES: A pCLE probe was positioned in non-dependent, central and dependent lung zones in nine anaesthetised pigs (Alveoflex, Cellvizio, Maunakea, France). After intravenous administration of fluorescein isothiocyanate dextran as contrast agent repetitive pCLE videos were recorded during pressure-controlled ventilation (PCV) or continuous positive airway pressure for 3 min each. Using fluorescein isothiocyanate-labelled RBC erythrocyte velocities in pulmonary capillaries were quantified. Data are expressed as mean ± SD or median with interquartile range (IQR). RESULTS: Capillary density was greater in dependent and central as compared with non-dependent lung zones [[32 (29 to 34) %] and 32 (30 to 34) % vs. 28 (26 to 28) %, respectively, P < 0.05]. During PCV, RBC velocities were higher in larger lung capillaries [diameter >20 µm, 309 µm s(-1) (209 to 397)] than intermediate [diameter 10.1 to 20 µm, 146 µm s(-1) (118 to 235)] and small [diameter <10 µm, 153 µm s(-1) (117 to 236), P <  .05]. During continuous positive airway pressure of 1.5 kPa, RBC velocities in dependent lung areas decreased to 47 µm s(-1) (30 to 82) compared with 198 µm s(-1) (148 to 290) during PCV (P < 0.05). CONCLUSION: pCLE allows endoscopic real-time in-vivo imaging of pulmonary capillary morphology and perfusion. Alterations in pulmonary capillary blood flow induced by different ventilator regimens can be detected. This minimally invasive approach via the endotracheal route is feasible in an experimental setting and may help to understand changes in regional pulmonary capillary perfusion.

Cerebrovascular autoregulation in critically ill patients during continuous hemodialysis.

PURPOSE: In chronic renal failure, intermittent hemodialysis decreases cerebral blood flow velocity (CBFV); however, in critically ill patients with acute renal failure, the effect of continuous venovenous hemodialysis (CVVHD) on CBFV and cerebrovascular autoregulation (AR) is unknown. Therefore, a study was undertaken to investigate the potential effect of CVVHD on CBFV and AR in patients with acute renal failure. METHODS: This cohort study investigated 20 patients with acute renal failure who required CVVHD. In these patients, the CBFV and index of AR (Mx) were measured using transcranial Doppler before and during CVVHD. RESULTS: The median Mx values at baseline were 0.33 [interquartile range (IQR): 0.02-0.55], and during CVVHD, they were 0.20 [0.07-0.40]. The differences in Mx (CVVHD--baseline) was (median [IQR]) -0.015 [-0.19-0.05], 95% confidence interval (CI) -0.16 to 0.05. The Mx was > 0.3 in 11/20 patients at baseline measurement. Six of these patients recovered to Mx < 0.3 during CVVHD. The CBFV was (median [IQR]) 47 [36-59] cm · sec(-1) at baseline and 49 [36-66] cm · sec(-1) during CVVHD. The difference of CBFV was 0.0 [-4 - 2.7], 95% CI -2.5 to 4.2. CONCLUSION: Compared with patients with intermittent hemodialysis, CVVHD did not influence CBFV and AR in critically ill patients with acute renal failure, possibly due to lower extracorporeal blood flow, slower change of plasma osmolarity, and a lower fluid extraction rate. In a subgroup of patients with sepsis, the AR was impaired at baseline in more than half of the patients, and this was reversed during CVVHD. The trial was registered at ClinicalTrials.gov ID: NCT01376531.

Transcranial doppler and near infrared spectroscopy in the perioperative period.

PURPOSE OF REVIEW: Maintenance of adequate blood flow and oxygen to the brain is one of the principal endpoints of all surgery and anesthesia. During operations in general anesthesia, however, the brain is at particular risk for silent ischemia. Despite this risk, the brain still remains one of the last monitored organs in clincial anesthesiology. RECENT FINDINGS: Transcranial Doppler (TCD) sonography and near-infrared spectroscopy (NIRS) experience a revival as these noninvasive technologies help to detect silent cerebral ischemia. TCD allows for quantification of blood flow velocities in basal intracranial arteries. TCD-derived variables such as the pulsatility index might hint toward diminished cognitive reserve or raised intracranial pressure. NIRS allows for assessment of regional cerebral oxygenation. Monitoring should be performed during high-risk surgery for silent cerebral ischemia and special circumstances during critical care medicine. Both techniques allow for the assessment of cerebrovascular autoregulation and individualized management of cerebral hemodynamics. SUMMARY: TCD and NIRS are noninvasive monitors that anesthesiologists apply to tailor cerebral oxygen delivery, aiming to safeguard brain function in the perioperative period.

[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.

Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium.

INTRODUCTION: Sepsis-associated delirium (SAD) increases morbidity in septic patients and, therefore, factors contributing to SAD should be further characterized. One possible mechanism might be the impairment of cerebrovascular autoregulation (AR) by sepsis, leading to cerebral hypo- or hyperperfusion in these haemodynamically unstable patients. Therefore, the present study investigates the relationship between the incidence of SAD and the status of AR during sepsis. METHODS: Cerebral blood flow velocity was measured using transcranial Doppler sonography and was correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was measured daily during the first 4 days of sepsis. Diagnosis of a SAD was performed using the confusion assessment method for ICU (CAM-ICU) and, furthermore the predominant brain electrical activity in electroencephalogram (EEG) both at day 4 after reduction of sedation to RASS >-2. RESULTS: 30 critically ill adult patients with severe sepsis or septic shock (APACHE II 32 ± 6) were included. AR was impaired at day 1 in 60%, day 2 in 59%, day 3 in 41% and day 4 in 46% of patients; SAD detected by CAM-ICU was present in 76 % of patients. Impaired AR at day 1 was associated with the incidence of SAD at day 4 (p = 0.035). CONCLUSIONS: AR is impaired in the great majority of patients with severe sepsis during the first two days. Impaired AR is associated with SAD, suggesting that dysfunction of AR is one of the trigger mechanisms contributing to the development of SAD. TRIAL REGISTRATION: clinicalTrials.gov ID NCT01029080.

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.

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-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.

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.

The effects of arterial carbon dioxide partial pressure and sevoflurane on capillary venous cerebral blood flow and oxygen saturation during craniotomy.

BACKGROUND: Intraoperative routine monitoring of cerebral blood flow and oxygenation remains a technological challenge. Using the physiological principle of carbon dioxide reactivity of cerebral vasculature, we investigated a recently developed neuromonitoring device (oxygen-to-see, O2C device) for simultaneous measurements of regional cerebral blood flow (rvCBF), blood flow velocity (rvVelo), oxygen saturation (srvO2), and hemoglobin amount (rvHb) at the capillary venous level in patients subjected to craniotomy. METHODS: Twenty-six neurosurgical patients were randomly assigned to anesthesia with 1.4% or 2.0% sevoflurane end-tidal concentration. After craniotomy, a fiberoptic probe was applied on a macroscopically healthy surface of cerebral tissue next to the site of surgery. Simultaneous measurements in 2 and 8 mm cerebral depth were performed in each patient during lower (35 mm Hg) and higher (45 mm Hg) levels (random order) of arterial carbon dioxide partial pressure (PaCO2). The principle of these measurements relies on the combination of laser-Doppler flowmetry (rvCBF, rvVelo) and photo-spectrometry (srvO2, rvHb). Linear models were fitted to test changes of end points (rvCBF, rvVelo, srvO2, rvHb) in response to lower and higher levels of PaCO2, 1.4% and 2.0% sevoflurane end-tidal concentration, and 2 and 8 mm cerebral depth. RESULTS: RvCBF and rvVelo were elevated by PaCO2 independent of sevoflurane concentration in 2 and 8 mm depth of cerebral tissue (P < 0.001). Higher PaCO2 induced an increase in mean srvO2 from 50% to 68% (P < 0.001). RvVelo (P < 0.001) and srvO2 (P = 0.007) were higher in 8 compared with 2 mm cerebral depth. RvHb was not influenced by alterations in PaCO2 but positively correlated to sevoflurane concentration (P = 0.005). CONCLUSIONS: Increases in rvCBF and rvVelo by PaCO2 suggest preserved hypercapnic vasodilation under anesthesia with sevoflurane 1.4% and 2.0% end-tidal concentration. A consecutive increase in srvO2 implies that cerebral arteriovenous difference in oxygen was decreased by elevated PaCO2. Unchanged levels of rvHb signify that there was no blood loss during measurements. Data suggest that the device allows detection of local changes in blood flow and oxygen saturation in response to different PaCO2 levels in predominant venous cerebral microvessels.

Recent advances in understanding acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by acute diffuse lung injury, which results in increased pulmonary vascular permeability and loss of aerated lung tissue. This causes bilateral opacity consistent with pulmonary edema, hypoxemia, increased venous admixture, and decreased lung compliance such that patients with ARDS need supportive care in the intensive care unit to maintain oxygenation and prevent adverse outcomes. Recently, advances in understanding the underlying pathophysiology of ARDS led to new approaches in managing these patients. In this review, we want to focus on recent scientific evidence in the field of ARDS research and discuss promising new developments in the treatment of this disease.