Aspiration of a Blister Pack Tablet with Tracheal Obstruction and Perforation: Emergency Tracheal Repair with Extracorporeal Membrane Oxygenation Support.

Background Airway management in case of acute tracheal injury is a challenging situation where the use of Extracorporeal Membrane Oxygenation (ECMO) has recently gained more importance. Case Description We report the case of a 60-year old women with aspiration of a large blister pack tablet causing acute tracheal obstruction with asphyxia as well as tracheal perforation with tension pneumothorax. As bronchoscopy failed to retrieve the blister pack, emergency tracheal reconstruction with Extracorporeal Membrane Oxygenation (ECMO) support was carried out. Conclusion The application of ECMO instantly alleviated the acute situation and provided excellent conditions for technically demanding emergency tracheal repair.

Outcome of Emergency Pulmonary Lobectomy under ECMO Support in Patients with COVID-19.

BACKGROUND: Not much is known about the results of nonelective anatomical lung resections in coronavirus disease 2019 (COVID-19) patients put on extracorporeal membrane oxygenation (ECMO). The aim of this study was to analyze the outcome of lobectomy under ECMO support in patients with acute respiratory failure due to severe COVID-19. METHODS: All COVID-19 patients undergoing anatomical lung resection with ECMO support at a German university hospital were included into a prospective database. Study period was April 1, 2020, to April 30, 2021 (first, second, and third waves in Germany). RESULTS: A total of nine patients (median age 61 years, interquartile range 10 years) were included. There was virtually no preexisting comorbidity (median Charlson score of comorbidity 0.2). The mean interval between first positive COVID-19 test and surgery was 21.9 days. Clinical symptoms at the time of surgery were sepsis (nine of nine), respiratory failure (nine of nine), acute renal failure (five of nine), pleural empyema (five of nine), lung artery embolism (four of nine), and pneumothorax (two of nine). Mean intensive care unit (ICU) and ECMO days before surgery were 15.4 and 6, respectively. Indications for surgery were bacterial superinfection with lung abscess formation and progressive septic shock (seven of nine) and abscess formation with massive pulmonary hemorrhage into the abscess cavity (two of nine). All patients were under venovenous ECMO with femoral-jugular configuration. Operative procedures were lobectomy (eight) and pneumonectomy (one). Weaning from ECMO was successful in four of nine. In-hospital mortality was five of nine. Mean total ECMO days were 10.3 ± 6.2 and mean total ICU days were 27.7 ± 9.9. Mean length of stay was 28.7 ± 8.8 days. CONCLUSION: Emergency surgery under ECMO support seems to open up a perspective for surgical source control in COVID-19 patients with bacterial superinfection and localized pulmonary abscess.

Accuracy of non-invasive sensors measuring core body temperature in cardiac surgery ICU patients - results from a monocentric prospective observational study.

PURPOSE: Temperature monitoring in the perioperative setting often represents a compromise between accuracy, invasiveness of probe placement, and patient comfort. Transcutaneous sensors using the Zero-Heat-Flux (ZHF) and Double-Sensor (DS) technology have been developed and evaluated in a variety of clinical settings. The present study is the first to compare the performance of both sensors simultaneously with temperature measured by a Swan-Ganz catheter (PAC) in patients admitted to the intensive care unit (ICU) after cardiac surgery. METHODS: In this monocentric prospective observational study patients were postoperatively transferred to the ICU and both sensors were placed on the patients' foreheads. Core body temperature measured by intraoperatively placed PAC served as gold standard. Measurements were recorded at 5-minute intervals and up to 40 data sets per patient were recorded. Bland and Altman's method for repeated measurements was used to analyse agreement. Subgroup analyses for gender, body-mass-index, core temperature, airway status and different time intervals were performed. Lin's concordance correlation coefficient (LCCC) was calculated, as well as sensitivity and specificity for detecting hyperthermia (≥ 38 °C) and hypothermia (< 36 °C). RESULTS: Over a period of six month, we collected 1600 sets of DS, ZHF, and PAC measurements, from a total of 40 patients. Bland-Altman analysis revealed a mean bias of -0.82 ± 1.27 °C (average ± 95% Limits-of-Agreement (LoA)) and - 0.54 ± 1.14 °C for DS and ZHF, respectively. The LCCC was 0.5 (DS) and 0.63 (ZHF). Mean bias was significantly higher in hyperthermic and hypothermic patients. Sensitivity and specificity were 0.12 / 0.99 (DS) and 0.35 / 1.0 (ZHF) for hyperthermia and 0.95 / 0.72 (DS) and 1.0 / 0.85 (ZHF) for hypothermia. CONCLUSION: Core temperature was generally underestimated by the non-invasive approaches. In our study, ZHF outperformed DS. In terms of agreement, results for both sensors were outside the range that is considered clinically acceptable. Nevertheless, both sensors might be adequate to detect postoperative hypothermia reliably when more invasive methods are not available or appropriate. TRIAL REGISTRATION: German Register of Clinical Trials (DRKS-ID: DRKS00027003), retrospectively registered 10/28/2021.

A model of porcine polymicrobial septic shock.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs. MATERIALS AND METHODS: The literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA. RESULTS: Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred. CONCLUSIONS: We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.

ICU- and ventilator-free days with isoflurane or propofol as a primary sedative - A post- hoc analysis of a randomized controlled trial.

PURPOSE: To compare ICU-free (ICU-FD) and ventilator-free days (VFD) in the 30 days after randomization in patients that received isoflurane or propofol without receiving the other sedative. MATERIALS AND METHODS: A recent randomized controlled trial (RCT) compared inhaled isoflurane via the Sedaconda® anaesthetic conserving device (ACD) with intravenous propofol for up to 54 h (Meiser et al. 2021). After end of study treatment, continued sedation was locally determined. Patients were eligible for this post-hoc analysis only if they had available 30-day follow-up data and never converted to the other drug in the 30 days from randomization. Data on ventilator use, ICU stay, concomitant sedative use, renal replacement therapy (RRT) and mortality were collected. RESULTS: Sixty-nine of 150 patients randomized to isoflurane and 109 of 151 patients randomized to propofol were eligible. After adjusting for potential confounders, the isoflurane group had more ICU-FD than the propofol group (17.3 vs 13.8 days, p = 0.028). VFD for the isoflurane and propofol groups were 19.8 and 18.5 respectively (p = 0.454). Other sedatives were used more frequently (p < 0.0001) and RRT started in a greater proportion of patients in the propofol group (p = 0.011). CONCLUSIONS: Isoflurane via the ACD was not associated with more VFD but with more ICU-FD and less concomitant sedative use.

Prolonged sedation with sevoflurane in comparison to intravenous sedation in critically ill patients - A randomized controlled trial.

BACKGROUND: Volatile anesthetics are used more commonly for sedation in the intensive-care-unit (ICU). However, evidence for long-term use remains low. We therefore conducted a randomized-controlled trial comparing sevoflurane with intravenous sedation with particular focus on efficacy and safety. METHODS: In this prospective, randomized-controlled phase-IIb monocentric clinical-trial ICU patients requiring at least 48 h of sedation were randomized to receive sevoflurane (S) or propofol/midazolam (P). Sedation quality was monitored using the Richmond-Agitation-Sedation-Scale. Following termination of sedation, the time to spontaneous breathing and extubation, opioid consumption, hemodynamics, ICU and hospital length of stay (LOS) and adverse events were recorded. RESULTS: 79 patients were eligible to randomization. Sedation quality was comparable between sevoflurane (n = 39) and propofol (n = 40). However, the use of sevoflurane lead to a reduction in time to spontaneous breathing (26 min vs. 375 min, P < 0.001). Patients sedated with propofol had lower opioid requirements (remifentanil:400 µg/h vs. 500 µg/h, P = 0.007; sufentanil:40 µg/h vs. 30 µg/h, P = 0.007) while hemodynamics, LOS or the occurrence of adverse events did not differ. CONCLUSION: ICU patients sedated with sevoflurane >48 h may return to spontaneous breathing faster, while the quality of sedation is comparable to a propofol-based sedation regime. Sevoflurane might be considered to be safe for long-term sedation in this patient population, while being non-inferior compared to propofol.

Isoflurane vs. propofol for sedation in invasively ventilated patients with acute hypoxemic respiratory failure: an a priori hypothesis substudy of a randomized controlled trial.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) is a leading concern in critically ill patients. Experimental and clinical data suggest that early sedation with volatile anesthestics may improve arterial oxygenation and reduce the plasma and alveolar levels of markers of alveolar epithelial injury and of proinflammatory cytokines. METHODS: An a priori hypothesis substudy of a multicenter randomized controlled trial (The Sedaconda trial, EUDRA CT Number 2016-004551-67). In the Sedaconda trial, 301 patients on invasive mechanical ventilation were randomized to 48 h of sedation with isoflurane or propofol in a 1:1 ratio. For the present substudy, patients with a ratio of arterial pressure of oxygen (PaO2) to inspired fraction of oxygen (FiO2), PaO2/FiO2, of ≤ 300 mmHg at baseline were included (n = 162). The primary endpoint was the change in PaO2/FiO2 between baseline and the end of study sedation. A subgroup analysis in patients with PaO2/FiO2 ≤ 200 mmHg was performed (n = 82). RESULTS: Between baseline and the end of study sedation (48 h), oxygenation improved to a similar extent in the isoflurane vs. the propofol group (isoflurane: 199 ± 58 to 219 ± 76 mmHg (n = 70), propofol: 202 ± 62 to 236 ± 77 mmHg (n = 89); p = 0.185). On day seven after randomization, PaO2/FiO2 was 210 ± 79 mmHg in the isoflurane group (n = 41) and 185 ± 87 mmHg in the propofol group (n = 44; p = 0.411). In the subgroup of patients with PaO2/FiO2 ≤ 200 mmHg, PaO2/FiO2 increase between baseline and end of study sedation was 152 ± 33 to 186 ± 54 mmHg for isoflurane (n = 37), and 150 ± 38 to 214 ± 85 mmHg for propofol (n = 45; p = 0.029). On day seven, PaO2/FiO2 was 198 ± 69 mmHg in patients randomized to isoflurane (n = 20) and 174 ± 106 mmHg in patients randomized to propofol (n = 20; p = 0.933). Both for the whole study population and for the subgroup with PaO2/FiO2 ≤ 200 mmHg, no significant between-group differences were observed for PaCO2, pH and tidal volume as well as 30-day mortality and ventilator-free days alive. CONCLUSIONS: In patients with AHRF, inhaled sedation with isoflurane for a duration of up to 48 h did not lead to improved oxygenation in comparison to intravenous sedation with propofol. Trial registration The main study was registered in the European Medicines Agency's EU Clinical Trial register (EudraCT), 2016-004551-67, before including the first patient. The present substudy was registered at German Clinical Trials Register (DRKS, ID: DRKS00018959) on January 7th, 2020, before opening the main study data base and obtaining access to study results.

Methaemoglobinemia after Liposuction under Tumescent Local Anaesthesia - Diagnostic Value of Pulse Oximetry.

Background: Tumescent local anaesthesia with prilocain can lead to clinically significant methemoglobin levels. New generation multiple wavelength pulse oximeters (e. g. Masimo Radical 7®) can measure methemoglobin levels. Methods: In this prospective observational study we compared the venous methemoglobin levels and the corresponding pulse oximetric values of the Radical 7® in patients undergoing tumescent local anaesthesia for liposuction procedures. The measurements were performed in Hanseklinik, Luebeck, Germany between 2008 and 2011. Results: In 133 patients, we measured a maximum methemoglobin level of 18 per cent. In a Bland-Altman analysis we found a mean bias of +2.2 % (-4.1 to 8.4 limits of agreement) for pulse oximetric values compared to hemoximetry. Conclusion: Pulse oximetric measurement of methemoglobin is an early-warning tool for the detection of clinically significant methaemoglobinemia in patients with tumescent local anaesthesia.

Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial.

BACKGROUND: Previous studies indicate that isoflurane could be useful for the sedation of patients in the intensive care unit (ICU), but prospective studies evaluating isoflurane's efficacy have been small. The aim of this study was to test whether the sedation with isoflurane was non-inferior to sedation with propofol. METHODS: This phase 3, randomised, controlled, open-label non-inferiority trial evaluated the efficacy and safety of up to 54 h of isoflurane compared with propofol in adults (aged ≥18 years) who were invasively ventilated in ICUs in Germany (21 sites) and Slovenia (three sites). Patients were randomly assigned (1:1) to isoflurane inhalation via the Sedaconda anaesthetic conserving device (ACD; Sedana Medical AB, Danderyd, Sweden; ACD-L [dead space 100 mL] or ACD-S [dead space 50 mL]) or intravenous propofol infusion (20 mg/mL) for 48 h (range 42-54) using permuted block randomisation with a centralised electronic randomisation system. The primary endpoint was percentage of time in Richmond Agitation-Sedation Scale (RASS) range -1 to -4, assessed in eligible participants with at least 12 h sedation (the per-protocol population), five or more RASS measurements, and no major protocol violations, with a non-inferiority margin of 15%. Key secondary endpoints were opioid requirements, spontaneous breathing, time to wake-up and extubation, and adverse events. Safety was assessed in all patients who received at least one dose. The trial is complete and registered with EudraCT, 2016-004551-67. FINDINGS: Between July 2, 2017, and Jan 12, 2020, 338 patients were enrolled and 301 (89%) were randomly assigned to isoflurane (n=150) or propofol (n=151). 146 patients (97%) in each group completed the 24-h follow-up. 146 (97%) patients in the isoflurane group and 148 (98%) of patients in the propofol group were included in the per-protocol analysis of the primary endpoint. Least-squares mean percentage of time in RASS target range was 90·7% (95% CI 86·8-94·6) for isoflurane and 91·1% (87·2-95·1) for propofol. With isoflurane sedation, opioid dose intensity was 29% lower than with propofol for the overall sedation period (0·22 [0·12-0·34] vs 0·32 [0·21-0·42] mg/kg per h morphine equivalent dose, p=0·0036) and spontaneous breathing was more frequent on day 1 (odds ratio [OR] 1·72 [1·12-2·64], generalised mixed linear model p=0·013, with estimated rates of 50% of observations with isoflurane vs 37% with propofol). Extubation times were short and median wake-up was significantly faster after isoflurane on day 2 (20 min [IQR 10-30] vs 30 min [11-120]; Cox regression p=0·0011). The most common adverse events by treatment group (isoflurane vs propofol) were: hypertension (ten [7%] of 150 vs two [1%] of 151), delirium (eight [5%] vs seven [5%]), oliguria (seven [5%] vs six [4%]), and atrial fibrillation (five [3%] vs four [3%]). INTERPRETATION: These results support the use of isoflurane in invasively ventilated patients who have a clinical need for sedation. FUNDING: Sedana Medical AB.

Depth of sedation during drug induced sedation endoscopy monitored by BiSpectral Index® and Cerebral State Index®.

PURPOSE: Drug induced sedation endoscopy (DISE) is performed to investigate patterns and sites of obstruction in patients with sleep-disordered breathing (SDB). During DISE the patients are sedated to obtain a muscular relaxation of the upper airway which mimics the relaxation during natural sleep. Different sleep stages are intended to be simulated by drug induced sedation, and it is helpful to measure the depth of sedation. The BiSpectral Index® (BIS) is often used for this procedure. Besides the BIS, other means of sedation depth monitoring exist in anaesthesiology but have not yet been investigated with respect to DISE. Monitoring of the Cerebral State Index® (CSI) is one of these methods. The aim of the study was to compare the BIS and CSI for sedation depth monitoring during DISE. METHODS: Sixty patients underwent DISE monitored by the BIS and CSI in parallel. The BIS and CSI values were compared using the Bland-Altman analysis. RESULTS: The BIS and CSI values differed during the course of sedation during DISE by a mean of - 6.07. At light sedation (BIS 60-80), lower values by 10 scale points of CSI compared with BIS were detectable. At deeper sedation levels (BIS 40-50), the CSI turned to present equal and even higher values compared with the BIS. CONCLUSION: Sedation depth measurement during DISE can be performed by the BIS or CSI, but the differences should be interpreted carefully as comparable data for sleep stages in natural sleep are available only for BIS.

The effects of systemic oxygenation on cerebral oxygen saturation and its relationship to mixed venous oxygen saturation: A prospective observational study comparison of the INVOS and ForeSight Elite cerebral oximeters.

PURPOSE: The present study aimed to test the hypothesis that cerebral oxygen saturation (ScO2) measurements with the INVOS-5100-C and the ForeSight-Elite cerebral oximeters vary in their correlation with mixed venous oxygen saturation (SvO2) upon changes in systemic oxygenation in extubated cardiac surgical patients. Additionally, we aimed to elucidate whether the ScO2 measurements of both devices can be used interchangeably to detect reduced SvO2. METHODS: Forty-eight spontaneously breathing patients extubated after cardiac surgery were included in this prospective observational study. The patients were exposed to both high (10 oxygen L·min-1 via face mask) and low (room air) inspiratory oxygen concentrations. Bi-hemispherical ScO2 was determined with the INVOS and ForeSight Elite cerebral oximeters. The SvO2 was measured with a pulmonary artery catheter. RESULTS: Significant changes in oxygen delivery, ScO2 (by both cerebral oximeters), and SvO2 were observed upon variation of oxygenation. The minimum mean (standard deviation) ScO2 (ScO2min) using the INVOS and ForeSight did not differ significantly during high oxygen delivery [63.1 (8.6) % vs 65.8 (4.7) %, respectively; P = 0.07], but during low oxygen delivery, the INVOS value was significantly lower than that of the ForeSight oximeter [56.7 (8.9) % vs 61.3 (4.4) %, respectively; P = 0.003]. Both devices differed in the correlation between ScO2min and SvO2 for the combined oxygenation data (0.59, INVOS vs 0.28, ForeSight; correlation difference, 0.31; Bonferroni-adjusted 95% confidence interval [CI], 0.08 to 0.54; P = 0.008). The receiver-operating curve analysis revealed an area under the curve of 0.83 (95% CI, 0.74 to 0.9; P = 0.005) for detecting an SvO2 below 50% by ScO2min with the INVOS and 0.51 (95% CI, 0.41 to 0.62; P = 0.92), respectively, with the ForeSight. CONCLUSIONS: These findings suggest that the cerebral oximeters tested react differently to variations in systemic oxygenation and in their relationship with SvO2 and thus give different information on cardiopulmonary function. These findings raise doubt about whether these devices should be used interchangeably.

Sevoflurane Abolishes Oxygenation Impairment in a Long-Term Rat Model of Acute Lung Injury.

BACKGROUND: Patients experiencing acute lung injury (ALI) often need mechanical ventilation for which sedation may be required. In such patients, usually the first choice an intravenously administered drug. However, growing evidence suggests that volatile anesthetics such as sevoflurane are a valuable alternative. In this study, we evaluate pulmonary and systemic effects of long-term (24-hour) sedation with sevoflurane compared with propofol in an in vivo animal model of ALI. METHODS: Adult male Wistar rats were subjected to ALI by intratracheal lipopolysaccharide (LPS) application, mechanically ventilated and sedated for varying intervals up to 24 hours with either sevoflurane or propofol. Vital parameters were monitored, and arterial blood gases were analyzed. Inflammation was assessed by the analysis of bronchoalveolar lavage fluid (BALF), cytokines (monocyte chemoattractant protein-1 [MCP-1], cytokine-induced neutrophil chemoattractant protein-1 [CINC-1], interleukin [IL-6], IL-12/12a, transforming growth factor-ß, and IL-10) in blood and lung tissue and inflammatory cells. The alveolocapillary barrier was indirectly assessed by wet-to-dry ratio, albumin, and total protein content in BALF. Results are presented as mean ± standard deviation. RESULTS: After 9 hours of ventilation and sedation, oxygenation index was higher in the LPS/sevoflurane (LPS-S) than in the LPS/propofol group (LPS-P) and reached 400 ± 67 versus 262 ± 57 mm Hg after 24 hours (P < .001). Cell count in BALF in sevoflurane-treated animals was lower after 18 hours (P = .001) and 24 hours (P < .001) than in propofol controls. Peak values of CINC-1 and IL-6 in BALF were lower in LPS-S versus LPS-P animals (CINC-1: 2.7 ± 0.7 vs 4.0 ± 0.9 ng/mL; IL-6: 9.2 ± 2.3 vs 18.9 ± 7.1 pg/mL, both P < .001), whereas IL-10 and MCP-1 did not differ. Also messenger RNAs of CINC-1, IL-6, IL-12a, and IL-10 were significantly higher in LPS-P compared with LPS-S. MCP-1 and transforming growth factor-ß showed no differences. Wet-to-dry ratio was lower in LPS-S (5.4 ± 0.2 vs 5.7 ± 0.2, P = .016). Total protein in BALF did not differ between P-LPS and S-LPS groups. CONCLUSIONS: Long-term sedation with sevoflurane compared with propofol improves oxygenation and attenuates the inflammatory response in LPS-induced ALI. Our findings suggest that sevoflurane may improve lung function when used for sedation in patients with ALI.

Procalcitonin Impairs Endothelial Cell Function and Viability.

BACKGROUND: Procalcitonin is used as a diagnostic tool for the identification and risk stratification of septic patients. Procalcitonin plasma concentrations tightly correlate with the severity of the ongoing inflammatory reaction and can rise up to 10,000-fold. Impairment of endothelial cell function plays an important role in the pathogenesis of hypotension and disturbed organ perfusion during sepsis. We investigated the possible effects of procalcitonin itself on endothelial cell function and viability. METHODS: Human endothelial cells were exposed to 0.01 to 100 ng/mL procalcitonin and investigated for endothelial permeability using transwells, migration in a scratch wound assay and new capillary formation on extracellular matrix in vitro. Tumor necrosis factor-α and vascular endothelial growth factor served as positive controls. Procalcitonin's impact on the response of endothelial cells toward ischemia was investigated in vivo in the murine model of unilateral femoral artery ligation. Procalcitonin-exposed endothelial cells were subjected to immunoblot for the investigation of vascular endothelial-cadherin expression and angiogenic signaling pathways. Flow cytometry was used for the detection of inflammatory activation and viability, and genomic analysis was performed. Data are presented as difference in means and 95% confidence intervals; statistical analyses were performed using analysis of variance/Bonferroni, and P values are reported as adjusted for multiple comparisons (Padjust). RESULTS: Tumor necrosis factor-α and 0.1 ng/mL procalcitonin induced endothelial barrier disruption after incubation of endothelial monolayers for 6 hours (-2.53 [-4.16 to -0.89], P = .0008 and -2.09 [-3.73 to -0.45], Padjust = .0064 compared with vehicle-treated control, respectively). Procalcitonin beginning at concentrations of 0.02 ng/mL reduced endothelial cell migration (0.26 [0.06 to 0.47], Padjust = .0069) and new capillary formation in vitro (0.47 [0.28 to 0.66], Padjust < .0001) contrasting the proangiogenic action of vascular endothelial growth factor. Left ventricular injection of procalcitonin in mice on postoperative day 1, 3, and 5 after induction of ischemia impaired new capillary formation and recovery of hindlimb perfusion in vivo (number of capillaries/mm in the ischemic leg of vehicle-treated versus procalcitonin-treated mice, 852.6 [383.4-1322], Padjust = .0002). Twenty-four-hour incubation with procalcitonin reduced the expression of vascular endothelial-cadherin at 100 ng/mL (0.39 [0.06-0.71], Padjust = .0167) and induced endothelial cell death (apoptosis, -5.4 [-10.67 to -0.13], Padjust = .0431). No alteration in the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 or extracellular signal-regulated kinase 1/2, and AKT signaling pathways was observed. Genomic analysis revealed regulation of a variety of genes involved in inflammation, angiogenesis, and cell growth. CONCLUSIONS: This study found that procalcitonin itself impaired several aspects of endothelial cell function. Procalcitonin-induced loss of endothelial barrier function may contribute to capillary leakage and therapy-refractory hypotension during sepsis. Anti-angiogenic properties of procalcitonin at low concentrations could also identify procalcitonin as a mediator of vascular disease associated with the metabolic syndrome. Future studies are needed to further test procalcitonin as a potential therapeutic target for preserving vascular dysfunction during acute and chronic inflammatory disorders.

Depth-dependent changes of obstruction patterns under increasing sedation during drug-induced sedation endoscopy: results of a German monocentric clinical trial.

PURPOSE: Drug-induced sedation endoscopy (DISE) and simulated snoring (SimS) can locate the site of obstruction in patients with sleep-disordered breathing (SDB). There is clinical evidence for a change in collapsibility of the upper airway depending on the depth of sedation. So far, a dose-response relationship between sedation and collapsibility has not been demonstrated. METHODS: DISE and SimS were performed in 60 consecutive patients with SDB under monitoring of depth of sedation by BiSpectral Index® (BIS). Initially, SimS was conducted followed by DISE using bolus application of propofol. Sedation was performed up to a sedation level representing slow wave sleep (BIS = 40). The collapsibility of the upper airway was documented at decreasing sedation levels by an identical pictogram classification. RESULTS: For all levels and patterns of obstruction, a dose-dependent increase in the collapsibility of the upper airway was detected. A maximum collapsibility was achieved at sedation levels representing slow wave sleep. The collapsibility during SimS corresponded to light sleep stages and did not cover slow wave sleep. CONCLUSION: A dose-dependent change of patterns of obstructions can be observed during DISE under BIS monitoring indicating sedation depth. The obtained patterns of obstruction during DISE and SimS should thus be interpreted with regard to the sedation depth.

Influence of different infracardial positions of central venous catheters in hemodynamic monitoring using the transpulmonal thermodilution method.

Hemodynamic measurements are often conducted by the transpulmonary thermodilution (TPTD)-based PiCCO(®)-system. This requires a central-venous (CVC) and a thermistor-tipped arterial catheter, usually placed in the femoral artery. In certain clinical situations, CVC devices have to be placed in the inferior vena cava. However, little is known about the influence of different CVC positions (i.e. ipsi- vs. contra-lateral to the arterial catheter) on the accuracy of the TPTD measurement results. In this prospective observational study surgical intensive care unit patients who had been inserted with CVCs either into the superior (CVCVCS) or the inferior vena cava (CVCinf) in addition to an arterial PiCCO(®)-catheter, were enrolled. Patients were then divided into two groups: Group I was provided with a CVC in the contralateral (CVCcontra) and Group II in the ipsilateral (CVCipsi) inferior vena cava. Thermodilution via injection of ice-cold saline was then performed via CVCsup and CVCinf. Bland-Altman analysis for cardiac index (CI), extra-vascular lung water index (EVLWI) and global end-diastolic volume index (GEDVI) were employed. Additional correction formulas for femorally assed parameters were determined. In a total of 28 patients, bias (limits of agreement) for measurements of CI in CVCcontra was found to be +0.2 (-0.4; +0.9) and +0.3 (-0.4; +1.0) L/min/m(2) in CVCipsi. GEDVI showed a bias of +274.8 (-47.3; +596.9) mL/m(2) in CVCcontra and +274.7 (-100.7; +650.1) mL/m(2) in CVCipsi. The mean EVLWI were 9.4 ± 4.3 mL/kg for EVLWIVCS and 10.7 ± 5.2 mL/kg for EVLWIinf. The LoA yielded at -3.4 and +6.1 mL/kg with a bias of +1.3 mL/kg. Percentage errors revealed clinically acceptable limits for CI and GEDVI, but not for EVLWI. Using TPTD via an infracardial central vein, measurements of CI showed high accuracy and precision while GEDVI measurements were precise with a lower accuracy, irrespective of the position of the infracardial CVC.

Drug-induced sleep endoscopy and simulated snoring in patients with sleep-disordered breathing: agreement of anatomic changes in the upper airway.

Drug-induced sleep endoscopy (DISE) and simulated snoring (SimS) are performed as part of the diagnostic procedure in patients with suspected sleep-disordered breathing (SDB). Despite both techniques frequently performed, they have rarely been evaluated yet in terms of agreement of the obtained results. Both diagnostic procedures were performed consecutively in 40 patients with SDB and documented identically. The obtained data were analysed with respect to the agreement of both procedure at different levels of the oropharynx as well as different patterns of obstruction and vibration. The anterior-posterior collapsibility of the soft palate/uvula revealed a moderate agreement between SimS and DISE (κ = 0.42; 95 % CI 0.22-0.63). The dorsal shift of the tongue base agreed moderate for patients with an AHI below 10 (κ = 0.47) and above 25 (κ = 0.44) between SimS ad DISE. The lateral and circular pharyngeal collapsibility at velum and tongue base level did not agree between SimS and DISE, was higher for DISE and could be partially reversed by mandibular protrusion. Collapse patterns of the soft palate and uvula can be induced by SimS and resemble the patterns induced by DISE. The dorsalization of the tongue base can be simulated to a lower extent by SimS. Lateral and circular patterns of collapse at the upper and lower oropharynx induced by DISE do not seem to be simulated by SimS. SimS seems to be an additional method to screen the collapsibility of the soft palate and uvula prior to DISE.

Evaluation of acoustic characteristics of snoring sounds obtained during drug-induced sleep endoscopy.

INTRODUCTION: Snoring sounds are discussed to contain acoustic information about their geneses. Nocturnal snoring can easily be recorded acoustically but it is difficult to visually verify its genesis. Contrary, snoring patterns induced by drug-induced sleep endoscopy (DISE) can be visually differentiated. The aim of the study was to classify patterns of obstructions and vibration during DISE and to evaluate acoustic characteristics between these different patterns of snoring. METHODS: DISE was performed in 41 male patients with sleep-disordered breathing. The recorded video sequences (n = 108) were classified visually at a mute mode in different patterns of snoring (velar, velar obstructive, tonsillar, post-apnoeic). The sound tracks of these subgroups were analysed and compared with regard to the parameters sound pressure level, loudness, sharpness, roughness, fluctuations strength and centre frequency. RESULTS: Obstructive snoring patterns revealed a higher loudness than non-obstructive patterns (>25 sone). Velar snoring showed more roughness (>150 cAsper) than tonsillar and post-apnoeic snoring and revealed the lowest centre frequency (<3000 Hz) of all patterns. Tonsillar snoring presented the highest sharpness (>1.6 acum) whereas post-apnoeic snoring revealed the largest fluctuation strength (>50 cVacil). CONCLUSION: Different snoring patterns induced by DISE can be classified visually, and an approach to differentiate them acoustically by means of psychoacoustic analyses is demonstrated. On the basis of these results, nocturnal snoring might also be differentiated by psychoacoustic algorithms which could be implemented in acoustic polygraphic screening devices in the future.

Antithrombin III, but not C1 esterase inhibitor reduces inflammatory response in lipopolysaccharide-stimulated human monocytes in an ex-vivo whole blood setting.

In order to examine the immunomodulatory effects of antithrombin III (AT-III) and C1 esterase inhibitor (C1-INH) in human monocytes, we investigated the intracellular expression of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in an ex-vivo laboratory study in a whole blood setting. Heparinized whole blood samples from 23 healthy male and female volunteers (mean age: 27±7years) were pre-incubated with clinically relevant concentrations of AT-III (n=11) and C1-INH (n=12), then stimulated with 0.2 ng/mL lipopolysaccharide (LPS) for 3h. After phenotyping CD14⁺ monocytes, intracellular expression of IL-6, IL-8, and TNF-α was assessed using flow cytometry. In addition, 12 whole blood samples (AT-III and C1-INH, n=6 each) were examined using hirudin for anticoagulation; all samples were processed in the same way. To exclude cytotoxicity effects, 7-amino-actinomycin D and Nonidet P40 staining were used to investigate probes. This study is the first to demonstrate the influence of C1-INH and AT-III on the monocytic inflammatory response in a whole blood setting, which mimics the optimal physiological setting. Cells treated with AT-III exhibited significant downregulation of the proportion of gated CD14⁺ monocytes for IL-6 and IL-8, in a dose-dependent manner; downregulation for TNF-α did not reach statistical significance. There were no significant effects on mean fluorescence intensity (MFI). In contrast, C1-INH did not significantly reduce the proportion of gated CD14⁺ monocytes or the MFI regarding IL-6, TNF-α, and IL-8. When using hirudin for anticoagulation, no difference in the anti-inflammatory properties of AT-III and C1-INH in monocytes occurs. Taken together, in contrast to TNF-α, IL-6 and IL-8 were significantly downregulated in monocytes in an ex-vivo setting of human whole blood when treated with AT-III. This finding implicates monocytes as an important point of action regarding the anti-inflammatory properties of AT-III in sepsis. C1-INH was unable to attenuate the monocytic response, which supports the hypothesis that other cellular components in whole blood (e.g., neutrophils) might be responsible for the known effects of C1-INH in inflammation.