Relapsing Polychondritis with Tracheobronchial Involvement: A Detailed Description of Two Pediatric Cases and Review of the Literature.

Relapsing polychondritis (RP) is a rare immune-mediated disease that primarily affects the cartilaginous structures of the ears, nose and airways. The clinical spectrum ranges from mild to severe disease characterized by progressive destruction of cartilage in the tracheobronchial tree leading to airway obstruction and acute respiratory failure. Early diagnosis is crucial to prevent irreversible airway damage and life-threatening complications. Due to its rarity and variability of symptoms, the diagnosis of RP is often delayed particularly in childhood. To address this and increase awareness of this rare disease, we present a detailed case report of two adolescent females affected by RP. We aim to describe the clinical findings, consequences of a delayed diagnosis and provide a review of the current literature.

Modification of Respiratory Drive and Lung Stress by Level of Support Pressure and ECMO Sweep Gas Flow in Patients With Severe COVID-19-Associated Acute Respiratory Distress Syndrome: an Exploratory Retrospective Analysis.

OBJECTIVES: Patients with severe acute respiratory distress syndrome (ARDS) often exhibit an unusually strong respiratory drive, which predisposes them to effort-induced lung injury. Careful titration of support pressure via the ventilator and carbon dioxide removal via extracorporeal membrane oxygenation (ECMO) may attenuate respiratory drive and lung stress. DESIGN: A retrospective cohort study. SETTING: At a single center, a university hospital. PARTICIPANTS: Ten patients with severe COVID-19-associated ARDS (CARDS) on venovenous ECMO therapy. INTERVENTIONS: Assessment of the effect of titrated support pressure and titrated ECMO sweep gas flow on respiratory drive and lung stress in spontaneously breathing patients during ECMO therapy. MEASUREMENTS AND MAIN RESULTS: Airway occlusion pressure (P0.1) and the total swing of the transpulmonary pressure were determined as surrogate parameters of respiratory drive and lung stress. Ventilator-mediated elevation of support pressure decreased P0.1 but increased transpulmonary driving pressure, airway pressure, tidal volume, and end-inspiratory transpulmonary occlusion pressure. The increase in ECMO sweep gas flow lowered P0.1, transpulmonary pressures, tidal volume, and respiratory frequency linearly. CONCLUSIONS: In patients with CARDS on pressure support ventilation, even moderate support pressure may lead to overassistance during assisted ventilation, which is only reflected by advanced monitoring of respiratory mechanics. Modifying carbon dioxide removal via the extracorporeal system profoundly affects respiratory effort and mechanics. Spontaneously breathing patients with CARDS may benefit from consequent carbon dioxide removal.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Association of radiological lung pattern and respiratory mechanics with potential for lung recruitment in patients with COVID-ARDS: a retrospective cohort study.

BACKGROUND: The ventilatory management of COVID-ARDS is controversial, especially with regard to the different subtypes and associated PEEP titration. A higher PEEP may be beneficial only in patients with potential for lung recruitment. The assessment of lung recruitment may be guided by lung imaging, such as electric impedance tomography or recruitment computed tomography, but is complex and not established in routine clinical practice. Therefore, bedside identification of recruitable ARDS phenotypes can aid in PEEP titration in clinical settings. METHODS: In this retrospective consecutive cohort study in 40 patients with moderate-to-severe COVID-ARDS, we assessed lung recruitment using the recruitment-to-inflation ratio (R/I) in moderate-to-severe COVID-ARDS. Evidence of recruitment (R/I ≥ 0.5) was compared between clinical and computed tomography data. RESULTS: Of the included patients, 28 (70%) were classified as recruiters by the R/I. Lung recruitment was associated with higher compliance and was not associated with a consolidated lung pattern assessed using CT. Even in the tertile of patients with the highest compliance (37-70 ml/mbar), eight (73%) patients were classified as recruitable. Patients classified as recruitable presented a lower reticular lung pattern (2% vs. 6%, p = 0.032). CONCLUSIONS: Prediction of lung recruitment is difficult based on routine clinical data but may be improved by assessment of radiographic lung patterns. A bedside assessment of recruitment is necessary to guide clinical care. Even a high compliance may not rule out the potential for lung recruitment.

The antipyretic effectiveness of dipyrone in the intensive care unit: A retrospective cohort study.

INTRODUCTION: Dipyrone (metamizol) is regularly used in critical care for pain and fever treatment, especially in Germany and Spain. However, indication for antipyretic therapy in critically ill patients is currently unclear and data for both the risk and benefit of dipyrone treatment in the intensive care environment are scarce. We hypothesized that antipyretic efficiency of dipyrone would not exceed antipyretic efficiency of acetaminophen. We therefore aimed to compare temperature courses in critically ill patients receiving either intravenous dipyrone, acetaminophen or no antipyretic medication. MATERIAL AND METHODS: We included 937 intensive care unit (ICU) patients with body temperature recordings of at least 37.5°C. We investigated temperature decrease associated with dipyrone or acetaminophen and additionally compared it to an untreated control group. RESULTS: Within the eight-hour study interval, maximum body temperature decrease in patients without antipyretic medication was -0.6°C (IQR: -1.0 to -0.4°C; n = 315). Maximal decrease in body temperature was higher both with dipyrone (-0.8°C (IQR: -1.2 to -0.4°C); p = 0.016; n = 341) and acetaminophen (-0.9°C (IQR: -1.6 to -0.6°C); p<0.001; n = 71), but did not differ between dipyrone and acetaminophen (p = 0.066). As compared to untreated patients, dipyrone only led to a marginal additional decrease in body temperature of only -0.1°C. Maximum of antipyretic effectiveness was reached four hours after administration. CONCLUSION: Antipyretic effectiveness of dipyrone in ICU patients may be overestimated. Given the lack of prospective data, clinical evidence for antipyretic dipyrone therapy in the ICU is insufficient and warrants further critical evaluation.

Effectiveness of amiodarone versus digitalis for heart rate control in critically ill patients with new-onset atrial fibrillation.

New-onset of atrial fibrillation (NOAF) in critically ill patients is the most common acute cardiac dysrhythmia, but evidence-based data regarding treatment strategies are scarce. In this retrospective monocentric study, we compared effectiveness of amiodarone versus digitalis for heart rate control in critically ill patients with new-onset of atrial fibrillation. We identified a total of 209 patients for the main analysis. Amiodarone as compared to digitalis was associated with a clinically relevant faster time to heart rate control < 110 bpm (2 h (IQR: 1 h to 6 h) versus 4 h (2 h to 12 h); p = 0.003) and longer durations of sinus rhythm during the first 24 h of treatment (6 h (IQR: 6 h to 22 h) versus 0 h (IQR: 0 h to 16 h); p < 0.001). However, more bradycardic episodes occurred in association with amiodarone than with digitalis (7.7% versus 3.4%; p = 0.019). Use of amiodarone was associated with an increase of noradrenalin infusion rate compared to digitalis (23.9% versus 12.0%; p = 0.019). Within the tertile of patients with the highest CRP measurements, amiodarone treated patients presented with a higher decrease in heart rate than digoxin treated patients. Clinical trials comparing different NOAF treatment strategies are much needed and should report on concomitant sympathetic activity and inflammatory status.

Spontaneous massive hemothorax as a complication of necrotizing pneumonia in a patient with severe acute respiratory syndrome coronavirus 2 induced acute respiratory distress syndrome: a case report.

BACKGROUND: We present an unusual bleeding complication in a patient with severe acute respiratory distress syndrome in coronavirus disease 2019. CASE PRESENTATION: The patient, a 63-year-old Caucasian man, received venovenous extracorporeal membrane oxygenation support after rapid deterioration of lung function on day 6 after admission to hospital. After initial stabilization on lung protective ventilation and prone positioning, he started to develop mild bleeding complications until he went into occult profound hemorrhagic shock. Causative was a massive hemothorax of the right hemithorax with mediastinal shifting due to spontaneous bleeding from a pulmonal artery in a heavily remodeled right inferior lobe. Histopathological examination of the resected tissue showed signs of an organizing fibrinous pneumonia with focal parenchyma necrosis. After surviving a massive bleeding event caused by necrotizing pneumonia, the patient made a swift recovery and was discharged to rehabilitation 31 days after initial hospital admission. CONCLUSIONS: The combination of severely elevated inflammatory markers and pulmonary hemorrhage should arouse suspicion of necrotizing pneumonia. In necrotizing pneumonia, the possibility of severe intrathoracic bleeding complications should be kept in mind if it comes to sudden deterioration of the patient.

Standardised electronic algorithms for monitoring prophylaxis of postoperative nausea and vomiting.

INTRODUCTION: Despite comprehensive guidelines with high-grade evidence, postoperative nausea and vomiting (PONV) remains a frequent problem in anaesthesia care. Anaesthesia information management systems (AIMS) may aid clinicians in PONV prevention, but their benefit is critically dependent on the details of implementation into practice. This study aimed to examine strengths and weaknesses of the local AIMS-based algorithm in prevention of PONV. MATERIAL AND METHODS: This retrospective study was conducted in the post-anaesthesia care unit (PACU) of a university hospital and included 10 604 patients aged 18 or older who were followed up in the PACU (intracranial, obstetrical or cardiothoracic surgery excluded) from March 2013 until March 2014. The PONV incidence in PACU and AIMS data validity were analysed. RESULTS: Adherence to PONV guideline recommendations was considerably low, with only 5749 (54%) of the patients receiving correct PONV prophylaxis. Two thousand seven hundred sixty-six (26%) of the patients received an insufficient PONV prophylaxis, which was associated with an excess PONV incidence (11% vs. 4% with correct prophylaxis, p < 0.001) in the PACU. Two thousand four hundred forty-nine (23%) of all patients were discharged from the PACU with an insufficient PONV prophylaxis despite perioperative digital PONV prevention algorithms. CONCLUSIONS: Adherence to PONV prophylaxis guidelines in the era of AIMS software and decision support is still remarkably low. The AIMS data usefulness depends on the user, the type of data input and the configuration of the software. Adherence to correct PONV prophylaxis should be re-evaluated systematically before discharge from PACU.

Determination of optimal positive end-expiratory pressure based on respiratory compliance and electrical impedance tomography: a pilot clinical comparative trial.

There is no agreement on gold standard method for positive end-expiratory pressure (PEEP) titration. Electrical impedance tomography (EIT) may aid in finding the optimal PEEP level. In this pilot trial, we investigated potential differences in the suggested optimal PEEP (BestPEEP) as derived by respiratory compliance and EIT-derived parameters. We examined if compliance-derived PEEP differs with regard to the regional ventilation distribution in relation to atelectasis and hyperinflation. Measurements were performed during an incremental/decremental PEEP trial in 15 ventilated intensive care patients suffering from mild-to-moderate impairment of oxygenation due to sepsis, pneumonia, trauma and metabolic and ischemic disorders. Measurement agreement was analyzed using Bland-Altman plots. We observed a diversity of EIT-derived and compliance-based optimal PEEP in the evaluated patients. BestPEEPCompliance did not necessarily correspond to the BestPEEPODCL with the least regional overdistension and collapse. The collapsed area was significantly smaller when the overdistension/collapse index was used for PEEP definition (p=0.022). Our results showed a clinically relevant difference in the suggested optimal PEEP levels when using different parameters for PEEP titration. The compliance-derived PEEP level revealed a higher proportion of residual regional atelectasis as compared to EIT-based PEEP.

Activation of the capsaicin-receptor TRPV1 by the acetaminophen metabolite N-arachidonoylaminophenol results in cytotoxicity.

AIMS: The anandamide reuptake inhibitor N-arachidonoylaminophenol (AM404) and the reactive substance N-acetyl-p-benzoquinone imine (NAPQI) are both metabolites of acetaminophen and may contribute to acetaminophen-induced analgesia by acting at TRPV1 expressed in the peripheral or central nervous system. While NAPQI slowly sensitizes and activates TRPV1 by interacting with distinct intracellular cysteine residues, detailed properties of AM404 as an agonist of TRPV1 have not yet been reported on. We explored the effects of AM404 on recombinant human TRPV1 and in rodent dorsal root ganglion (DRG) neurons. MATERIALS AND METHODS: HEK 293 cells expressing different isoforms of recombinant TRPV1 and rodent DRG neurons were employed for patch clamp and calcium imaging experiments. Cytotoxicity was assessed by propidium iodide and Annexin V staining on TRPV1-HEK 293 cells and with trypan blue staining on DRG neurons. KEY FINDINGS: AM404 activates hTRPV1 at concentrations >1µM and in a concentration-dependent manner. AM404 also potentiates TRPV1-mediated currents evoked by heat and anandamide. Moreover, AM404-evoked currents are potentiated by NAPQI. While the partly capsaicin-insensitive rabbit (o) TRPV1 fails to respond to AM404, AM404-sensitivity is restored by insertion of the capsaicin binding-domain of rat TRPV1 into oTRPV1. In DRG neurons, AM404-evoked calcium influx as well as cell death is mediated by TRPV1. SIGNIFICANCE: AM404 gates TRPV1 by interacting with the vanilloid-binding site, and TRPV1 is the main receptor for AM404 in DRG neurons. While direct activation of TRPV1 requires high concentrations of AM404, it is possible that synergistic effects of AM404 with further TRPV1-agonists may occur at clinically relevant concentrations.

TRPA1 and TRPV1 are required for lidocaine-evoked calcium influx and neuropeptide release but not cytotoxicity in mouse sensory neurons.

BACKGROUND: Local anaesthetics (LA) reduce neuronal excitability by inhibiting voltage-gated Na+ channels. When applied at high concentrations in the direct vicinity of nerves, LAs can also induce relevant irritation and neurotoxicity via mechanisms involving an increase of intracellular Ca2+. In the present study we explored the role of the Ca2+-permeable ion channels TRPA1 and TRPV1 for lidocaine-induced Ca2+-influx, neuropeptide release and neurotoxicity in mouse sensory neurons. METHODS: Cultured dorsal root ganglion (DRG) neurons from wildtype and mutant mice lacking TRPV1, TRPA1 or both channels were explored by means of calcium imaging, whole-cell patch clamp recordings and trypan blue staining for cell death. Release of calcitonin gene-related peptide (CGRP) from isolated mouse peripheral nerves was determined with ELISA. RESULTS: Lidocaine up to 10 mM induced a concentration-dependent reversible increase in intracellular Ca2+ in DRG neurons from wildtype and mutant mice lacking one of the two receptors, but not in neurons lacking both TRPA1 and TRPV1. 30 mM lidocaine also released Ca2+ from intracellular stores, presumably from the endoplasmic reticulum. While 10 mM lidocaine evoked an axonal CGRP release requiring expression of either TRPA1 or TRPV1, CGRP release induced by 30 mM lidocaine again mobilized internal Ca2+ stores. Lidocaine-evoked cell death required neither TRPV1 nor TRPA1. SUMMARY: Depending on the concentration, lidocaine employs TRPV1, TRPA1 and intracellular Ca2+ stores to induce a Ca2+-dependent release of the neuropeptide CGRP. Lidocaine-evoked cell death does not seem to require Ca2+ influx through TRPV1 or TRPV1.

Differential cytotoxicity and intracellular calcium-signalling following activation of the calcium-permeable ion channels TRPV1 and TRPA1.

Several members of the transient receptor channel (TRP) family can mediate a calcium-dependent cytotoxicity. In sensory neurons, vanilloids like capsaicin induce neurotoxicity by activating TRPV1. The closely related ion channel TRPA1 is also activated by irritants, but it is unclear if and how TRPA1 mediates cell death. In the present study we explored cytotoxicity and intracellular calcium signalling resulting from activation of TRPV1 and TRPA1, either heterologously expressed in HEK 293 cells or in native mouse dorsal root ganglion (DRG) neurons. While activation of TRPV1 by the vanilloids capsaicin, resiniferatoxin and anandamide results in calcium-dependent cell death, activation by protons and the oxidant chloramine-T failed to reduce cell viability. The TRPA1-agonists acrolein, carvacrol and capsazepine all induced cytotoxicity, but this effect is independent of TRPA1. Activation of both TRPA1 and TRPV1 triggers a strong influx of external calcium, but also a strong calcium-release from intracellular stores most likely including the endoplasmic reticulum (ER). Activation of TRPV1, but not TRPA1 also results in a strong increase of mitochondrial calcium both in HEK 293 cells and mouse DRG neurons. Our data demonstrate that activation of TRPV1, but not TRPA1 mediates a calcium-dependent cell death. While both receptors mediate a release of calcium from intracellular stores, only activation of TRPV1 seems to mediate a robust and probably lethal increase in mitochondrial calcium.

Investigation into the role of an extracellular loop in mediating proton-evoked inhibition of voltage-gated sodium channels.

Proton-evoked activation of sensory neurons is counteracted by inhibition of voltage-gated Na+ channels, and the low acid-sensitivity of sensory neuron of the African naked mole-rat (ANMr) was reported to be due to a strong proton-evoked block of ANMrNav1.7. Here we aimed to reevaluate the role of the suggested negatively-charged motif in the ANMrNav1.7 domain IV P-loop for inhibition by protons. Patch clamp recordings were performed on the recombinant α-subunits Nav1.2-1.8. The insertion of the negatively charged motif (EKE) of ANMrNav1.7 into human Nav1.7 results in an increased proton-evoked tonic inhibition, but also in a reduced channel function. While the voltage-dependency of fast inactivation is changed in hNav1.7-EKE, pH 6.4 fails to induce a significant shift in both constructs. Proton-evoked inhibition of other channel α-subunits reveals a discrete differential inhibition among α-subunits with hNav1.7 displaying the lowest proton-sensitivity. The mutant hNav1.7-EKE displays a similar proton-sensitivity as Nav1.2, Nav1.3, Nav1.6 and Nav1.8. Overall, a correlation between proton-evoked inhibition and motif charge was not evident. Accordingly, a homology model of hNav1.7 shows that the EKE motif residues do not contribute to the pore lumen. Our data confirms that a negative charge of a postulated proton-motif encodes for a high proton-sensitivity when inserted into hNav1.7. However, a negatively charged motif is not a reliable predictor for a high proton-sensitivity in other α-subunits. Given the distance of the proton-motif from the pore mouth it seems unlikely that a blocking mechanism involving direct obstruction of the pore underlies the observed proton-evoked channel inhibition.

The use of dipyrone in the ICU is associated with acute kidney injury: A retrospective cohort analysis.

BACKGROUND: Use of dipyrone (metamizole) in perioperative and ICU pain therapy remains controversial due to a lack of solid evidence weighing dipyrone benefit against its potential life-threatening complications. Although dipyrone has known analgesic and antipyretic properties, its mechanisms of actions are incompletely understood. Although dipyrone effects on renal vasodilator prostaglandin synthesis are documented, little is known about its potential renal side effects, especially in the critical care environment. OBJECTIVE: Investigation of the perioperative nephrotoxic potential of dipyrone in patients prone to acute kidney injury (AKI). DESIGN: Retrospective cohort study. SETTING: Single centre study in a tertiary referral hospital from January 2013 until June 2013. PATIENTS: A total of 500 consecutive patients aged 18 years and older referred to the anaesthesia ICU. Patients were excluded if admitted from or discharged to other ICUs, if referred for post resuscitation care, or if repeatedly admitted to the ICU. MAIN OUTCOME MEASURES: Incidence of AKI, as defined by the Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group criteria, and duration of vasopressor therapy. RESULTS: Use of dipyrone was associated with an increased incidence of AKI in a dose-dependent manner with a 1.6-fold increase in the incidence of AKI with each additional gram of intravenous dipyrone per day. Dipyrone dose of more than 2.5 g day was the best risk predictive cut-off for AKI. Patients receiving dipyrone on the ICU presented with a prolonged duration of vasopressor therapy. CONCLUSION: Increasing dipyrone dosage is a potential independent risk factor for AKI in adult ICU patients and may prolong vasopressor therapy. Clinical evidence for a benefit of dipyrone therapy in the ICU is insufficient and needs further critical evaluation.

Influence of intraoperative positive end-expiratory pressure level on pulmonary complications in emergency major trauma surgery.

INTRODUCTION: Pulmonary complications have a major impact on the morbidity and mortality of critically ill patients with multiple trauma. Intraoperative protective ventilation with low tidal volume may prevent lung injury and infection, whereas the role of positive end-expiratory pressure (PEEP) levels is unclear. The aim of this study was to evaluate the influence of different intraoperative PEEP levels on incidence of pulmonary complications after emergency trauma surgery. MATERIAL AND METHODS: We retrospectively analysed data of multiple trauma patients who underwent emergency surgery within 24 h after injury in our level I trauma centre (n = 86). On the basis of their intraoperative PEEP level, patients were divided into a low PEEP group with a PEEP of < 8 mbar and a high PEEP group with a PEEP of 8 mbar or higher. RESULTS: Besides differences in body mass index and preoperative oxygenation, there were no differences in patients' baseline data. There was a significant difference between incidence of pneumonia within 7 days after trauma surgery, with an incidence 26.7% in the low PEEP group and 7.3% in the high PEEP group (p = 0.02). The low PEEP group had higher pulmonary infection scores at days 3 and 5 after surgery. Oxygenation was better in the higher PEEP group postoperatively. There was no difference with respect to the incidence of acute respiratory distress syndrome, the mortality up until hospital discharge or haemodynamic parameters between groups. CONCLUSIONS: Higher PEEP levels were associated with perioperative improvement of oxygenation and a lower incidence of pneumonia, without impairment of haemodynamics. Additional studies should be initiated to confirm these observations.

Quaternary Lidocaine Derivative QX-314 Activates and Permeates Human TRPV1 and TRPA1 to Produce Inhibition of Sodium Channels and Cytotoxicity.

BACKGROUND: The relatively membrane-impermeable lidocaine derivative QX-314 has been reported to permeate the ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1) to induce a selective inhibition of sensory neurons. This approach is effective in rodents, but it also seems to be associated with neurotoxicity. The authors examined whether the human isoforms of TRPV1 and TRPA1 allow intracellular entry of QX-314 to mediate sodium channel inhibition and cytotoxicity. METHODS: Human embryonic kidney 293 (HEK-293) cells expressing wild-type or mutant human (h) TRPV1 or TRPA1 constructs as well as the sodium channel Nav1.7 were investigated by means of patch clamp and ratiometric calcium imaging. Cytotoxicity was examined by flow cytometry. RESULTS: Activation of hTRPA1 by carvacrol and hTRPV1 by capsaicin produced a QX-314-independent reduction of sodium current amplitudes. However, permeation of QX-314 through hTRPV1 or hTRPA1 was evident by a concentration-dependent, use-dependent inhibition of Nav1.7 activated at 10 Hz. Five and 30 mM QX-314 activated hTRPV1 via mechanisms involving the intracellular vanilloid-binding domain and hTRPA1 via unknown mechanisms independent of intracellular cysteins. Expression of hTRPV1, but not hTRPA1, was associated with a QX-314-induced cytotoxicity (viable cells 48 ± 5% after 30 mM QX-314) that was ameliorated by the TRPV1 antagonist 4-(3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide (viable cells 81 ± 5%). CONCLUSIONS: The study data demonstrate that QX-314 directly activates and permeates the human isoforms of TRPV1 and TRPA1 to induce inhibition of sodium channels, but also a TRPV1-dependent cytotoxicity. These results warrant further validation of this approach in more intact preparations and may be valuable for the development of this concept into clinical practice.

Influence of different electrode belt positions on electrical impedance tomography imaging of regional ventilation: a prospective observational study.

BACKGROUND: Electrical impedance tomography (EIT) is a non-invasive bedside tool which allows an individualized ventilator strategy by monitoring tidal ventilation and lung aeration. EIT can be performed at different cranio-caudal thoracic levels, but data are missing about the optimal belt position. The main goal of this prospective observational study was to evaluate the impact of different electrode layers on tidal impedance variation in relation to global volume changes in order to propose a proper belt position for EIT measurements. METHODS: EIT measurements were performed in 15 mechanically ventilated intensive care patients with the electrode belt at different thoracic layers (L1-L7). All respiratory and hemodynamic parameters were recorded. Blood gas analyses were obtained once at the beginning of EIT examination. Off-line tidal impedance variation/tidal volume (TV/VT) ratio was calculated, and specific patterns of impedance distribution due to automatic and user-defined adjustment of the colour scale for EIT images were identified. RESULTS: TV/VT ratio is the highest at L1. It decreases in caudal direction. At L5, the decrease of TV/VT ratio is significant. We could identify patterns of diaphragmatic interference with ventilation-related impedance changes, which owing to the automatically adjusted colour scales are not obvious in the regularly displayed EIT images. CONCLUSIONS: The clinical usability and plausibility of EIT measurements depend on proper belt position, proper impedance visualisation, correct analysis and data interpretation. When EIT is used to estimate global parameters like VT or changes in end-expiratory lung volume, the best electrode plane is between the 4th and 5th intercostal space. The specific colour coding occasionally suppresses user-relevant information, and manual rescaling of images is necessary to visualise this information.

Differential cytotoxic properties of drugs used for intra-articular injection on human chondrocytes: an experimental in-vitro study.

BACKGROUND: Intra-articular injection of local anaesthetics, opioids and corticosteroids is frequently used to obtain perioperative analgesia following joint surgery. Although local anaesthetics were shown to induce chondrotoxicity, the safety profile regarding chondrotoxicity of other injected drugs is less clear. OBJECTIVE: Our objective was to investigate cytotoxicity of drugs used for intra-articular analgesia. DESIGN: An experimental in-vitro study. SETTING: Hannover Medical School, science laboratory, 2013. MATERIAL: Human cartilage cell line T/C 28-a2. INTERVENTION: Incubation of cells with different concentrations of bupivacaine, s-ketamine, morphine and dexamethasone for 1 h. MAIN OUTCOME MEASURES: Fraction of Annexin V positive and Annexin V and propidium iodide double positive cells after 1 h of incubation with tested drug measured by flow cytometry. RESULTS: Both morphine (0.1 to 10 µmol l) and dexamethasone (10 to 1000 µmol/l) failed to induce cytotoxicity after 1 h of exposure. The previously reported chondrotoxicity of bupivacaine (10 to 500 µmol l or 2.8 to 140 µg ml) was confirmed by a concentration-dependent increased staining with Annexin V and propidium iodide. Exposure to S-ketamine (10 to 500 µmol l) induced a significant late apoptotic and necrotic cell fraction at 10 µmol l or 2.4 µg ml. Concentrations of 100 and 500 µmol l induced a significant increase in early apoptotic cells. CONCLUSION: Morphine and dexamethasone showed no cytotoxic effects in our study and might thus be better alternatives to the clinically frequently applied bupivacaine. S-ketamine induced an intensive dose-dependent cytotoxic effect and should probably be avoided for intra-articular injection.