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1. Determinants of acute kidney injury during high-power mechanical ventilation: secondary analysis from experimental data

Author: Simone Gattarello, Fabio Lombardo, Federica Romitti, Rosanna D’Albo, Mara Velati, Isabella Fratti, Tommaso Pozzi, Rosmery Nicolardi, Antonio Fioccola, Mattia Busana, Francesca Collino, Peter Herrmann, Luigi Camporota, Michael Quintel, Onnen Moerer, Leif Saager, Konrad Meissner, and Luciano Gattinoni
Subjects: Mean perfusion pressure, Mean arterial pressure, Central venous pressure, Acute kidney injury, Acute kidney failure, Mechanical power, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The individual components of mechanical ventilation may have distinct effects on kidney perfusion and on the risk of developing acute kidney injury; we aimed to explore ventilatory predictors of acute kidney failure and the hemodynamic changes consequent to experimental high-power mechanical ventilation. Methods Secondary analysis of two animal studies focused on the outcomes of different mechanical power settings, including 78 pigs mechanically ventilated with high mechanical power for 48 h. The animals were categorized in four groups in accordance with the RIFLE criteria for acute kidney injury (AKI), using the end-experimental creatinine: (1) NO AKI: no increase in creatinine; (2) RIFLE 1-Risk: increase of creatinine of > 50%; (3) RIFLE 2-Injury: two-fold increase of creatinine; (4) RIFLE 3-Failure: three-fold increase of creatinine; Results The main ventilatory parameter associated with AKI was the positive end-expiratory pressure (PEEP) component of mechanical power. At 30 min from the initiation of high mechanical power ventilation, the heart rate and the pulmonary artery pressure progressively increased from group NO AKI to group RIFLE 3. At 48 h, the hemodynamic variables associated with AKI were the heart rate, cardiac output, mean perfusion pressure (the difference between mean arterial and central venous pressures) and central venous pressure. Linear regression and receiving operator characteristic analyses showed that PEEP-induced changes in mean perfusion pressure (mainly due to an increase in CVP) had the strongest association with AKI. Conclusions In an experimental setting of ventilation with high mechanical power, higher PEEP had the strongest association with AKI. The most likely physiological determinant of AKI was an increase of pleural pressure and CVP with reduced mean perfusion pressure. These changes resulted from PEEP per se and from increase in fluid administration to compensate for hemodynamic impairment consequent to high PEEP;
Published: 2024
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2. Prone position: how understanding and clinical application of a technique progress with time

Author: Luciano Gattinoni, Serena Brusatori, Rosanna D’Albo, Roberta Maj, Mara Velati, Carmelo Zinnato, Simone Gattarello, Fabio Lombardo, Isabella Fratti, Federica Romitti, Leif Saager, Luigi Camporota, and Mattia Busana
Subjects: Prone position, Gas exchange, Lung mechanics, ARDS, Covid-19, Anesthesiology, RD78.3-87.3
Abstract: Abstract Historical background The prone position was first proposed on theoretical background in 1974 (more advantageous distribution of mechanical ventilation). The first clinical report on 5 ARDS patients in 1976 showed remarkable improvement of oxygenation after pronation. Pathophysiology The findings in CT scans enhanced the use of prone position in ARDS patients. The main mechanism of the improved gas exchange seen in the prone position is nowadays attributed to a dorsal ventilatory recruitment, with a substantially unchanged distribution of perfusion. Regardless of the gas exchange, the primary effect of the prone position is a more homogenous distribution of ventilation, stress and strain, with similar size of pulmonary units in dorsal and ventral regions. In contrast, in the supine position the ventral regions are more expanded compared with the dorsal regions, which leads to greater ventral stress and strain, induced by mechanical ventilation. Outcome in ARDS The number of clinical studies paralleled the evolution of the pathophysiological understanding. The first two clinical trials in 2001 and 2004 were based on the hypothesis that better oxygenation would lead to a better survival and the studies were more focused on gas exchange than on lung mechanics. The equations better oxygenation = better survival was disproved by these and other larger trials (ARMA trial). However, the first studies provided signals that some survival advantages were possible in a more severe ARDS, where both oxygenation and lung mechanics were impaired. The PROSEVA trial finally showed the benefits of prone position on mortality supporting the thesis that the clinical advantages of prone position, instead of improved gas exchange, were mainly due to a less harmful mechanical ventilation and better distribution of stress and strain. In less severe ARDS, in spite of a better gas exchange, reduced mechanical stress and strain, and improved oxygenation, prone position was ineffective on outcome. Prone position and COVID-19 The mechanisms of oxygenation impairment in early COVID-19 are different than in typical ARDS and relate more on perfusion alteration than on alveolar consolidation/collapse, which are minimal in the early phase. Bronchial shunt may also contribute to the early COVID-19 hypoxemia. Therefore, in this phase, the oxygenation improvement in prone position is due to a better matching of local ventilation and perfusion, primarily caused by the perfusion component. Unfortunately, the conditions for improved outcomes, i.e. a better distribution of stress and strain, are almost absent in this phase of COVID-19 disease, as the lung parenchyma is nearly fully inflated. Due to some contradictory results, further studies are needed to better investigate the effect of prone position on outcome in COVID-19 patients. Graphical Abstract
Published: 2023
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3. Epidural Needle Guidance Using Viscoelastic Tissue Response

Author: Benjamin Scott Simpson, Michael Burns, Robert P. Dick, and Leif Saager
Subjects: Epidural, needle placement, viscoelastic response, machine learning, biomedical engineering, Computer applications to medicine. Medical informatics, R858-859.7, Medical technology, R855-855.5
Abstract: Objective: We designed, prototyped, and tested a system that measures the viscoelastic response of tissue using nondestructive mechanical probing, with the goal of aiding clinical providers during epidural needle placement. This system is meant to alert clinicians when an epidural needle is about to strike bone during insertion. Methods: During needle insertion, the system periodically mechanically stimulates and collects viscoelastic response information data from the tissue at the needle’s tip using an intra-needle probe. A machine-learning algorithm detects when the needle is close to bone using the series of observed stimulations. Results: Tests run on ex vivo pig spine show that the system can reliably determine if the needle is pointed at and within 3 mm of bone. Conclusion: Our technique can successfully differentiate materials at and in front of the needle’s tip. However, it does not provide the 5 mm of forewarning that we believe would be necessary for use in clinical epidural needle placement. The technique may be of use in other applications requiring tissue differentiation during needle placement or in the intended application with further technical advances. Clinical and Translational Impact Statement: This Early/Pre-Clinical Research evaluates the feasibility of a method for helping clinical providers receive feedback during epidural needle insertion—thereby reducing complication rates—without significant alterations from current workflow.
Published: 2022
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4. High class filtering facepiece (FFP) are fundamental and effective in protection of emergency health care workers: an observational cohort study in a German community

Author: Martin Lier, Stefan Nessler, Christine Stadelmann, Meike Pressler, Leif Saager, Onnen Moerer, Markus Roessler, Konrad Meissner, and Martin S. Winkler
Subjects: Personal protection equipment, Filtering facepiece, FFP2, N95, SARS-CoV-2, Seroprevalence, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious airborne virus inducing pandemic coronavirus disease 2019 (COVID-19). This is most relevant for medical staff working under harmful conditions in emergencies often dealing with patients and an undefined SARS-CoV-2 status. We aimed to measure the effect of high-class filtering facepieces (FFP) in emergency medical service (EMS) staff by analyzing seroprevalence and history of positive polymerase chain reaction (PCR) for SARS-CoV-2. Method This observational cohort study included workers in EMS, who were compared with hospital staff (HS) and staff, which was not directly involved in patient care (NPC). All direct patient contacts of EMS workers were protected by FFP2/N95 (filtering face piece protection class 2/non-oil-based particulates filter efficiency 95%) masks, whereas HS was protected by FFP2/N95 exclusively when a patient had a proven or suspected SARS-CoV-2 infection. NPC was not protected by higher FFP. The seroprevalence of SARS-CoV-2 antibodies was analyzed by immunoassay by end of 12/2020 together with the history of a positive PCR. In addition, a self-assessment was performed regarding the quantity of SARS-CoV-2 positive contacts, about flu symptoms and personal belief of previous COVID-19 infections. Results The period in which contact to SARS-CoV-2 positive patients has been possible was 10 months (March to December 2020)—with 54,681 patient contacts documented for EMS—either emergencies (n = 33,241) or transportation services (n = 21,440). Seven hundred-thirty (n = 730) participants were included into the study (n = EMS: 325, HS: 322 and NPC: 83). The analysis of the survey showed that the exposure to patients with an unknown and consecutive positive SARS-CoV-2 result was significantly higher for EMS when compared to HS (EMS 55% vs. HS 30%, p = 0.01). The incidence of a SARS-CoV-2 infection in our cohort was 1.2% (EMS), 2.2% (HS) and 2.4% (NPC) within the three groups (ns) and lowest in EMS. Furthermore, the belief of previous COVID-19 was significant higher in EMS (19% vs. 10%), Conclusion The consistent use of FFP2/N95 in EMS is able to prevent work-related SARS-CoV-2 infections in emergency situations. The significance of physical airway protection in exposed medical staff is still relevant especially under the aspect of new viral variants and unclear effectiveness of new vaccines. Graphical Abstract
Published: 2021
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5. End-tidal to arterial PCO2 ratio: a bedside meter of the overall gas exchanger performance

Author: Matteo Bonifazi, Federica Romitti, Mattia Busana, Maria Michela Palumbo, Irene Steinberg, Simone Gattarello, Paola Palermo, Leif Saager, Konrad Meissner, Michael Quintel, Davide Chiumello, and Luciano Gattinoni
Subjects: PETCO2, Acute respiratory distress syndrome, Severity, Monitoring, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Abstract Background The physiological dead space is a strong indicator of severity and outcome of acute respiratory distress syndrome (ARDS). The “ideal” alveolar PCO2, in equilibrium with pulmonary capillary PCO2, is a central concept in the physiological dead space measurement. As it cannot be measured, it is surrogated by arterial PCO2 which, unfortunately, may be far higher than ideal alveolar PCO2, when the right-to-left venous admixture is present. The “ideal” alveolar PCO2 equals the end-tidal PCO2 (PETCO2) only in absence of alveolar dead space. Therefore, in the perfect gas exchanger (alveolar dead space = 0, venous admixture = 0), the PETCO2/PaCO2 is 1, as PETCO2, PACO2 and PaCO2 are equal. Our aim is to investigate if and at which extent the PETCO2/PaCO2, a comprehensive meter of the “gas exchanger” performance, is related to the anatomo physiological characteristics in ARDS. Results We retrospectively studied 200 patients with ARDS. The source was a database in which we collected since 2003 all the patients enrolled in different CT scan studies. The PETCO2/PaCO2, measured at 5 cmH2O airway pressure, significantly decreased from mild to mild–moderate moderate–severe and severe ARDS. The overall populations was divided into four groups (~ 50 patients each) according to the quartiles of the PETCO2/PaCO2 (lowest ratio, the worst = group 1, highest ratio, the best = group 4). The progressive increase PETCO2/PaCO2 from quartile 1 to 4 (i.e., the progressive approach to the “perfect” gas exchanger value of 1.0) was associated with a significant decrease of non-aerated tissue, inohomogeneity index and increase of well-aerated tissue. The respiratory system elastance significantly improved from quartile 1 to 4, as well as the PaO2/FiO2 and PaCO2. The improvement of PETCO2/PaCO2 was also associated with a significant decrease of physiological dead space and venous admixture. When PEEP was increased from 5 to 15 cmH2O, the greatest improvement of non-aerated tissue, PaO2 and venous admixture were observed in quartile 1 of PETCO2/PaCO2 and the worst deterioration of dead space in quartile 4. Conclusion The ratio PETCO2/PaCO2 is highly correlated with CT scan, physiological and clinical variables. It appears as an excellent measure of the overall “gas exchanger” status.
Published: 2021
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6. Opioid-induced respiratory depression increases hospital costs and length of stay in patients recovering on the general care floor

Author: Ashish K. Khanna, Leif Saager, Sergio D. Bergese, Carla R. Jungquist, Hiroshi Morimatsu, Shoichi Uezono, Lian Kah Ti, Roy Soto, Wei Jiang, and Wolfgang Buhre
Subjects: Respiratory depression, Healthcare utilization, Opioids, Detection, Post-operative, Patient safety, Anesthesiology, RD78.3-87.3
Abstract: Abstract Background Opioid-induced respiratory depression is common on the general care floor. However, the clinical and economic burden of respiratory depression is not well-described. The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial created a prediction tool to identify patients at risk of respiratory depression. The purpose of this retrospective sub-analysis was to examine healthcare utilization and hospital cost associated with respiratory depression. Methods One thousand three hundred thirty-five patients (N = 769 United States patients) enrolled in the PRODIGY trial received parenteral opioids and underwent continuous capnography and pulse oximetry monitoring. Cost data was retrospectively collected for 420 United States patients. Differences in healthcare utilization and costs between patients with and without ≥1 respiratory depression episode were determined. The impact of respiratory depression on hospital cost per patient was evaluated using a propensity weighted generalized linear model. Results Patients with ≥1 respiratory depression episode had a longer length of stay (6.4 ± 7.8 days vs 5.0 ± 4.3 days, p = 0.009) and higher hospital cost ($21,892 ± $11,540 vs $18,206 ± $10,864, p = 0.002) compared to patients without respiratory depression. Patients at high risk for respiratory depression, determined using the PRODIGY risk prediction tool, who had ≥1 respiratory depression episode had higher hospital costs compared to high risk patients without respiratory depression ($21,948 ± $9128 vs $18,474 ± $9767, p = 0.0495). Propensity weighted analysis identified 17% higher costs for patients with ≥1 respiratory depression episode (p = 0.007). Length of stay significantly increased total cost, with cost increasing exponentially for patients with ≥1 respiratory depression episode as length of stay increased. Conclusions Respiratory depression on the general care floor is associated with a significantly longer length of stay and increased hospital costs. Early identification of patients at risk for respiratory depression, along with early proactive intervention, may reduce the incidence of respiratory depression and its associated clinical and economic burden. Trial registration ClinicalTrials.gov , NCT02811302 .
Published: 2021
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7. Mechanical power thresholds during mechanical ventilation: An experimental study

Author: Federica Romitti, Mattia Busana, Maria Michela Palumbo, Matteo Bonifazi, Lorenzo Giosa, Francesco Vassalli, Alessandro Gatta, Francesca Collino, Irene Steinberg, Simone Gattarello, Stefano Lazzari, Paola Palermo, Ahmed Nasr, Ann‐Kathrin Gersmann, Annika Richter, Peter Herrmann, Onnen Moerer, Leif Saager, Luigi Camporota, John J. Marini, Michael Quintel, Konrad Meissner, and Luciano Gattinoni
Subjects: mechanical power, mechanical ventilation, treshold, ventilation induced lung injury, Physiology, QP1-981
Abstract: Abstract The extent of ventilator‐induced lung injury may be related to the intensity of mechanical ventilation––expressed as mechanical power. In the present study, we investigated whether there is a safe threshold, below which lung damage is absent. Three groups of six healthy pigs (29.5 ± 2.5 kg) were ventilated prone for 48 h at mechanical power of 3, 7, or 12 J/min. Strain never exceeded 1.0. PEEP was set at 4 cmH2O. Lung volumes were measured every 12 h; respiratory, hemodynamics, and gas exchange variables every 6. End‐experiment histological findings were compared with a control group of eight pigs which did not undergo mechanical ventilation. Functional residual capacity decreased by 10.4% ± 10.6% and 8.1% ± 12.1% in the 7 J and 12 J groups (p = 0.017, p
Published: 2022
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8. Role of Fluid and Sodium Retention in Experimental Ventilator-Induced Lung Injury

Author: Simone Gattarello, Iacopo Pasticci, Mattia Busana, Stefano Lazzari, Paola Palermo, Maria Michela Palumbo, Federica Romitti, Irene Steinberg, Francesca Collino, Francesco Vassalli, Thomas Langer, Onnen Moerer, Leif Saager, Peter Herrmann, Paolo Cadringher, Konrad Meissner, Michael Quintel, and Luciano Gattinoni
Subjects: ventilation-induced lung injury, mechanical ventilation, fluid balance, sodium retention, non-osmotic sodium, Physiology, QP1-981
Abstract: Background: Ventilator-induced lung injury (VILI) via respiratory mechanics is deeply interwoven with hemodynamic, kidney and fluid/electrolyte changes. We aimed to assess the role of positive fluid balance in the framework of ventilation-induced lung injury.Methods:Post-hoc analysis of seventy-eight pigs invasively ventilated for 48 h with mechanical power ranging from 18 to 137 J/min and divided into two groups: high vs. low pleural pressure (10.0 ± 2.8 vs. 4.4 ± 1.5 cmH2O; p < 0.01). Respiratory mechanics, hemodynamics, fluid, sodium and osmotic balances, were assessed at 0, 6, 12, 24, 48 h. Sodium distribution between intracellular, extracellular and non-osmotic sodium storage compartments was estimated assuming osmotic equilibrium. Lung weight, wet-to-dry ratios of lung, kidney, liver, bowel and muscle were measured at the end of the experiment.Results: High pleural pressure group had significant higher cardiac output (2.96 ± 0.92 vs. 3.41 ± 1.68 L/min; p < 0.01), use of norepinephrine/epinephrine (1.76 ± 3.31 vs. 5.79 ± 9.69 mcg/kg; p < 0.01) and total fluid infusions (3.06 ± 2.32 vs. 4.04 ± 3.04 L; p < 0.01). This hemodynamic status was associated with significantly increased sodium and fluid retention (at 48 h, respectively, 601.3 ± 334.7 vs. 1073.2 ± 525.9 mmol, p < 0.01; and 2.99 ± 2.54 vs. 6.66 ± 3.87 L, p < 0.01). Ten percent of the infused sodium was stored in an osmotically inactive compartment. Increasing fluid and sodium retention was positively associated with lung-weight (R2 = 0.43, p < 0.01; R2 = 0.48, p < 0.01) and with wet-to-dry ratio of the lungs (R2 = 0.14, p < 0.01; R2 = 0.18, p < 0.01) and kidneys (R2 = 0.11, p = 0.02; R2 = 0.12, p = 0.01).Conclusion: Increased mechanical power and pleural pressures dictated an increase in hemodynamic support resulting in proportionally increased sodium and fluid retention and pulmonary edema.
Published: 2021
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9. Using Artificial Intelligence for Automatic Segmentation of CT Lung Images in Acute Respiratory Distress Syndrome

Author: Peter Herrmann, Mattia Busana, Massimo Cressoni, Joachim Lotz, Onnen Moerer, Leif Saager, Konrad Meissner, Michael Quintel, and Luciano Gattinoni
Subjects: ARDS, fully automatic lung segmentation, deep learning, U-Net, LabVIEW, DeepLTK, Physiology, QP1-981
Abstract: Knowledge of gas volume, tissue mass and recruitability measured by the quantitative CT scan analysis (CT-qa) is important when setting the mechanical ventilation in acute respiratory distress syndrome (ARDS). Yet, the manual segmentation of the lung requires a considerable workload. Our goal was to provide an automatic, clinically applicable and reliable lung segmentation procedure. Therefore, a convolutional neural network (CNN) was used to train an artificial intelligence (AI) algorithm on 15 healthy subjects (1,302 slices), 100 ARDS patients (12,279 slices), and 20 COVID-19 (1,817 slices). Eighty percent of this populations was used for training, 20% for testing. The AI and manual segmentation at slice level were compared by intersection over union (IoU). The CT-qa variables were compared by regression and Bland Altman analysis. The AI-segmentation of a single patient required 5–10 s vs. 1–2 h of the manual. At slice level, the algorithm showed on the test set an IOU across all CT slices of 91.3 ± 10.0, 85.2 ± 13.9, and 84.7 ± 14.0%, and across all lung volumes of 96.3 ± 0.6, 88.9 ± 3.1, and 86.3 ± 6.5% for normal lungs, ARDS and COVID-19, respectively, with a U-shape in the performance: better in the lung middle region, worse at the apex and base. At patient level, on the test set, the total lung volume measured by AI and manual segmentation had a R2 of 0.99 and a bias −9.8 ml [CI: +56.0/−75.7 ml]. The recruitability measured with manual and AI-segmentation, as change in non-aerated tissue fraction had a bias of +0.3% [CI: +6.2/−5.5%] and −0.5% [CI: +2.3/−3.3%] expressed as change in well-aerated tissue fraction. The AI-powered lung segmentation provided fast and clinically reliable results. It is able to segment the lungs of seriously ill ARDS patients fully automatically.
Published: 2021
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10. International multicentre observational study to evaluate the association between perioperative red blood cell transfusions and 1-year mortality after major cancer surgery (ARCA-1): study design, statistical analysis plan and study protocol

Author: Lei Feng, Patrice Forget, Juan Cata, Ary Serpa Neto, Maria Ramirez, Lee-Lynn Chen, Oscar Diaz-Cambronero, Wankun Chen, Matthew A Warner, Adriana Knopfelmacher Couchonal, Paolo Pelosi, Luis Cuellar, German Corrales, Carlos Romero, Francisco Lobo, Leif Saager, Jorge Castro Tapia, and Roy Kiberenge
Subjects: Medicine
Abstract: Introduction Blood transfusion is still common in patients undergoing major cancer surgery. Blood transfusion can be associated with poor prognosis in patients with cancer. Perioperative Care in the Cancer Patient -1 (ARCA-1) aims to assess in a large cohort of patients the current incidence, pattern of practice and associations between perioperative blood transfusions and 1-year survival in patients undergoing major cancer surgery.Methods and analysis ARCA-1 is a prospective international multicentre observational study that will include adult patients scheduled to have major cancer surgical procedures with the intention to cure, and an overnight planned hospital admission. The study will be opened for 1 year for enrolment (7 January 2020–7 February 2021). Each centre will enrol patients for 30 days. The primary endpoint of this study is all-cause mortality 1 year after major cancer surgery. Secondary endpoints are rate of perioperative blood product use, cancer-specific mortality at 1 year and PFSs and 30-day morbidity and mortality.Ethics and dissemination This study was approved by the Institutional Review Board at The University of Texas—MD Anderson Cancer Center. The study results will be published in peer-reviewed journals and disseminated at international conferences.Trial registration number NCT04491409.
Published: 2021
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11. Hands-Off Time for Endotracheal Intubation during CPR Is Not Altered by the Use of the C-MAC Video-Laryngoscope Compared to Conventional Direct Laryngoscopy. A Randomized Crossover Manikin Study.

Author: Philipp Schuerner, Bastian Grande, Tobias Piegeler, Martin Schlaepfer, Leif Saager, Matthew T Hutcherson, Donat R Spahn, and Kurt Ruetzler
Subjects: Medicine, Science
Abstract: INTRODUCTION:Sufficient ventilation and oxygenation through proper airway management is essential in patients undergoing cardio-pulmonary resuscitation (CPR). Although widely discussed, securing the airway using an endotracheal tube is considered the standard of care. Endotracheal intubation may be challenging and causes prolonged interruption of chest compressions. Videolaryngoscopes have been introduced to better visualize the vocal cords and accelerate intubation, which makes endotracheal intubation much safer and may contribute to intubation success. Therefore, we aimed to compare hands-off time and intubation success of direct laryngoscopy with videolaryngoscopy (C-MAC, Karl Storz, Tuttlingen, Germany) in a randomized, cross-over manikin study. METHODS:Twenty-six anesthesia residents and twelve anesthesia consultants of the University Hospital Zurich were recruited through a voluntary enrolment. All participants performed endotracheal intubation using direct laryngoscopy and C-MAC in a random order during ongoing chest compressions. Participants were strictly advised to stop chest compression only if necessary. RESULTS:The median hands-off time was 1.9 seconds in direct laryngoscopy, compared to 3 seconds in the C-MAC group. In direct laryngoscopy 39 intubation attempts were recorded, resulting in an overall first intubation attempt success rate of 97%, compared to 38 intubation attempts and 100% overall first intubation attempt success rate in the C-MAC group. CONCLUSION:As a conclusion, the results of our manikin-study demonstrate that video laryngoscopes might not be beneficial compared to conventional, direct laryngoscopy in easily accessible airways under CPR conditions and in experienced hands. The benefits of video laryngoscopes are of course more distinct in overcoming difficult airways, as it converts a potential "blind intubation" into an intubation under visual control.
Published: 2016
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12. Low vitamin D concentration is not associated with increased mortality and morbidity after cardiac surgery.

Author: Alparslan Turan, Martin Grady, Jing You, Edward J Mascha, Worasak Keeyapaj, Ryu Komatsu, C Allen Bashour, Daniel I Sessler, Leif Saager, and Andrea Kurz
Subjects: Medicine, Science
Abstract: To determine the effect of vitamin D on postoperative outcomes in cardiac surgical patients.Retrospective study.Single institution-teaching hospital.Adult cardiac surgical patients with perioperative 25-hydroxyvitamin D measurements.None. We gathered information from the Cardiac Anesthesiology Registry that was obtained at the time of the patients' visit/hospitalization.We used data of 18,064 patients from the Cardiac Anesthesiology Registry; 426 patients with 25-hydroxyvitamin D measurements met our inclusion criteria. Association with Vitamin D concentration and composite of 11 cardiac morbidities was done by multivariate (i.e., multiple outcomes per subject) analysis. For other outcomes separate multivariable logistic regressions and adjusting for the potential confounders was used. The observed median vitamin D concentration was 19 [Q1-Q3∶12, 30] ng/mL. Vitamin D concentration was not associated with our primary composite of serious cardiac morbidities (odds ratio [OR], 0.96; 95% CI, 0.86-1.07). Vitamin D concentration was also not associated with any of the secondary outcomes: neurologic morbidity (P = 0.27), surgical (P = 0.26) or systemic infections (P = 0.58), 30-day mortality (P = 0.55), or length of initial intensive care unit (ICU) stay (P = 0.04).Our analysis suggests that perioperative vitamin D concentration is not associated with clinically important outcomes, likely because the outcomes are overwhelmingly determined by other baseline and surgical factors.
Published: 2013
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13. Target insertion depth of nasopharyngeal temperature probes in children: A prospective observational study analyzing magnetic resonance images

Author: Clemens Miller, Anselm Bräuer, Thomas Asendorf, Marielle Ernst, Philipp von Gottberg, Juliane Richter, Leif Saager, and Marcus Nemeth
Subjects: Anesthesiology and Pain Medicine, Child, Preschool, Nasopharynx, Pediatrics, Perinatology and Child Health, Temperature, Humans, Infant, Prospective Studies, Child, Magnetic Resonance Imaging, Body Height, Body Temperature
Abstract: Core temperature monitoring is indispensable to prevent children from perioperative thermal perturbations. Although nasopharyngeal measurements are commonly used in anesthesia and considered to reflect core temperature accurately, standardized target depths for probe insertion are unknown in children.Our primary goal was to determine a target depth of nasopharyngeal temperature probe insertion in children by measuring distances on magnetic resonance imaging (MRI). Secondary aims were to correlate these measurements with biometric variables and facial landmark-distances to derive formulas estimating target depth.We conducted a prospective observational study in children ≤12 years undergoing cranial MRI with anesthesia. We documented patient characteristics and measured the landmark-distances nostril-mandible, nostril-tragus, and philtrum-tragus on patient's faces. On MRI, the target point for the probe tip was considered to be the site of the nasopharyngeal mucosa with the closest proximity to the internal carotid artery. After its determination in the transverse axis and triangulation to the sagittal axis, we measured the distance to the nostril. This distance, defined as target insertion depth, was correlated with the patient characteristics and used for univariate and multiple linear regression analysis.One hundred twenty children with a mean age of 4.5 years were included. The target insertion depth ranged from 61.8 mm in infants to 89.8 mm in 12-year-old children. Height correlated best (ρ = 0.685, 95%-CI: [0.57-0.77]). The best-fit estimation in millimeters, "40.8 + height [cm] × 0.32,″ would lead to a placement in the target position in 67% of cases. A simplified approach by categories of 50-80, 80-110, 110-130, and130 cm height with target insertion depths of 60, 70, 80, and 85 mm, respectively, achieved similar probabilities.Height-based formulas could be a valuable proxy for the insertion depth of nasopharyngeal temperature probes. Further clinical trials are necessary to investigate their measurement accuracy.
Published: 2022

14. The role of the TMS parameters for activation of the corticospinal pathway to the diaphragm

Author: Ivan, Chakalov, Andrea, Antal, Simon S, Eckardt, Walter, Paulus, Leif, Saager, Konrad, Meissner, Mathias, Bähr, Onnen, Moerer, and Caspar, Stephani
Subjects: Neurology, Electromyography, Physiology (medical), Diaphragm, Motor Cortex, Pyramidal Tracts, Humans, Reproducibility of Results, Neurology (clinical), Evoked Potentials, Motor, Transcranial Magnetic Stimulation, Sensory Systems
Abstract: The influence of the TMS-parameters on the efficacy and reliability to induce diaphragmatic motor-evoked potentials (diMEPs) has not been studied so far. Therefore, the objective of the present research is to probe the role of TMS- waveform (monophasic- [Mo] vs. biphasic-pulses [Bi]) and current direction (posterior-anterior [Pa] vs. anterior-posterior [Ap]) in the activation of the diaphragm.Four different pulse-configurations (Mo-Ap, Mo-Pa, Bi-Ap, Bi-Pa) were applied by means of neuronavigated-TMS and surface MEP-recordings at relaxed end-expiration in 19 healthy subjects. The parameters resting motor threshold (RMT), diMEP-amplitude and -latency, as well as best stimulation site (motor hotspot) and central motor conduction time were studied. Diaphragm movements were simultaneously recorded via ultrasound. To control for possible signal contamination the MEPs of muscles neighboring the diaphragm were also obtained.The motor hotspots of the diaphragm showed similar spatial distribution for the Mo-Ap, Mo-Pa, Bi-Ap and Bi-Pa. The biphasic-pulses yielded significantly lower RMTs and higher diMEP-amplitudes as the monophasic-pulses. Anterior to posterior oriented Bi- and Mo-pulses evoked significantly shorter diMEP-latencies than the posterior-anterior oriented ones.The present research demonstrates that biphasic- as compared to monophasic-pulses require significantly less charge and time for inducing diMEPs.The biphasic-TMS is best suited for the demanding stimulation of the diaphragm.
Published: 2022

15. Evaluation of the noninvasive Temple Touch Pro temperature monitoring system compared with oesophageal temperature in paediatric anaesthesia (PETER PAN): A prospective observational study

Author: Marcus Nemeth, Katharina Klose, Thomas Asendorf, Carlo Pancaro, Benjamin Mielke, Albulena Fazliu, Leif Saager, Anselm Bräuer, and Clemens Miller
Subjects: Anesthesiology and Pain Medicine
Abstract: Monitoring peri-operative body temperature in children is currently mainly achieved through invasive devices. The Temple Touch Pro Temperature Monitoring System estimates core temperature noninvasively based on heat flux thermometry.To investigate the agreement of this noninvasive sensor against standard oesophageal core temperature.A prospective observational study.University hospital recruiting between April and July 2021.One hundred children (32 girls) aged 6 years or younger scheduled for noncardiac surgery, resulting in 6766 data pairs. Exclusion criteria were contraindication for the insertion of an oesophageal temperature probe, and procedures in which one of the measurement methods would interfere with the surgical field.Primary outcome was the agreement analysis by a Bland-Altman comparison with multiple measurements. Posthoc, we performed another agreement analysis after exclusion of a statistically determined equilibration time. Secondary outcomes were the temperature differences over time and subgroup analysis of hypothermic, normothermic and hyperthermic temperature ranges, age, sex and sensor's side by type III analysis of variance. Further, we correlated the sonographically determined depth of the artery with trueness.The mean difference was -0.07°C (95% CI -0.15 to +0.05) with limits of agreement of -1.00 and +0.85°C. After adjusting for an equilibration time of 13 min, the mean difference improved to -0.04°C (95% CI -0.08 to +0.01) with limits of agreement of -0.68 and +0.60°C. Concordance correlation coefficient was 0.83 (95% CI 0.82 to 0.84). Differences between the skin sensor and oesophageal reference increased over time by -0.05°C per hour. Subgroup analysis showed no clinically relevant differences. Depth of artery negatively correlated with trueness by 0.03°C per millimetre.Although the Temple Touch Pro sensor showed acceptable accuracy after allowing for an equilibration time, it still needs further investigation for routine use in children. This particularly affects accuracy in hypothermic ranges, imprecise positioning and applicability in children with immature or vulnerable skin.German Clinical Trials Register, identifier: DRKS00024703.
Published: 2023

16. Mechanical power ratio and respiratory treatment escalation in COVID-19 pneumonia: a secondary analysis of a prospectively enrolled cohort

Author: Simone Gattarello, Silvia Coppola, Elena Chiodaroli, Tommaso Pozzi, Luigi Camporota, Leif Saager, Davide Chiumello, and Luciano Gattinoni
Subjects: Anesthesiology and Pain Medicine, Settore MED/41 - Anestesiologia
Abstract: Background Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with a higher risk of respiratory failure, this study assessed lung mechanics in nonintubated patients with COVID-19 pneumonia, aiming to (1) describe their characteristics; (2) compare lung mechanics between patients who received respiratory treatment escalation and those who did not; and (3) identify variables associated with the need for respiratory treatment escalation. Methods Secondary analysis of prospectively enrolled cohort involving 111 consecutive spontaneously breathing adults receiving continuous positive airway pressure, enrolled from September 2020 to December 2021. Lung mechanics and other previously reported predictive indices were calculated, as well as a novel variable: the mechanical power ratio (the ratio between the actual and the expected baseline mechanical power). Patients were grouped according to the outcome: (1) no-treatment escalation (patient supported in continuous positive airway pressure until improvement) and (2) treatment escalation (escalation of the respiratory support to noninvasive or invasive mechanical ventilation), and the association between lung mechanics/predictive scores and outcome was assessed. Results At day 1, patients undergoing treatment escalation had spontaneous tidal volume similar to those of patients who did not (7.1 ± 1.9 vs. 7.1 ± 1.4 ml/kgIBW; P = 0.990). In contrast, they showed higher respiratory rate (20 ± 5 vs. 18 ± 5 breaths/min; P = 0.028), minute ventilation (9.2 ± 3.0 vs. 7.9 ± 2.4 l/min; P = 0.011), tidal pleural pressure (8.1 ± 3.7 vs. 6.0 ± 3.1 cm H2O; P = 0.003), mechanical power ratio (2.4 ± 1.4 vs. 1.7 ± 1.5; P = 0.042), and lower partial pressure of alveolar oxygen/fractional inspired oxygen tension (174 ± 64 vs. 220 ± 95; P = 0.007). The mechanical power (area under the curve, 0.738; 95% CI, 0.636 to 0.839] P < 0.001), the mechanical power ratio (area under the curve, 0.734; 95% CI, 0.625 to 0.844; P < 0.001), and the pressure-rate index (area under the curve, 0.733; 95% CI, 0.631 to 0.835; P < 0.001) showed the highest areas under the curve. Conclusions In this COVID-19 cohort, tidal volume was similar in patients undergoing treatment escalation and in patients who did not; mechanical power, its ratio, and pressure-rate index were the variables presenting the highest association with the clinical outcome. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2022

17. Mechanisms of oxygenation responses to proning and recruitment in COVID-19 pneumonia

Author: Luigi Camporota, Mattia Busana, Stefano Lazzari, Sandra Rossi, Laura Malchiodi, Maria Michela Palumbo, Matteo Bonifazi, Paola Palermo, Simone Gattarello, Federica Romitti, Luciano Gattinoni, John J. Marini, Massimo Cressoni, Peter Herrmann, Irene Steinberg, Leif Saager, Patrizia Ceccarelli, Paolo Bresciani, Emanuele Sani, Konrad Meissner, Michael Quintel, Nicola Sverzellati, and Francesca Collino
Subjects: medicine.medical_specialty, ARDS, Supine position, medicine.medical_treatment, Lung recruitment, Atelectasis, Critical Care and Intensive Care Medicine, Mechanical ventilation, Internal medicine, Correspondence, Prone Position, medicine, Humans, Prospective Studies, Lung, Respiratory Distress Syndrome, Pulmonary Gas Exchange, SARS-CoV-2, business.industry, COVID-19, Oxygenation, respiratory system, medicine.disease, respiratory tract diseases, Prone position, medicine.anatomical_structure, Cardiology, business, Perfusion
Abstract: This study aimed at investigating the mechanisms underlying the oxygenation response to proning and recruitment maneuvers in coronavirus disease 2019 (COVID-19) pneumonia. Twenty-five patients with COVID-19 pneumonia, at variable times since admission (from 1 to 3 weeks), underwent computed tomography (CT) lung scans, gas-exchange and lung-mechanics measurement in supine and prone positions at 5 cmH2O and during recruiting maneuver (supine, 35 cmH2O). Within the non-aerated tissue, we differentiated the atelectatic and consolidated tissue (recruitable and non-recruitable at 35 cmH2O of airway pressure). Positive/negative response to proning/recruitment was defined as increase/decrease of PaO2/FiO2. Apparent perfusion ratio was computed as venous admixture/non aerated tissue fraction. The average values of venous admixture and PaO2/FiO2 ratio were similar in supine-5 and prone-5. However, the PaO2/FiO2 changes (increasing in 65% of the patients and decreasing in 35%, from supine to prone) correlated with the balance between resolution of dorsal atelectasis and formation of ventral atelectasis (p = 0.002). Dorsal consolidated tissue determined this balance, being inversely related with dorsal recruitment (p = 0.012). From supine-5 to supine-35, the apparent perfusion ratio increased from 1.38 ± 0.71 to 2.15 ± 1.15 (p = 0.004) while PaO2/FiO2 ratio increased in 52% and decreased in 48% of patients. Non-responders had consolidated tissue fraction of 0.27 ± 0.1 vs. 0.18 ± 0.1 in the responding cohort (p = 0.04). Consolidated tissue, PaCO2 and respiratory system elastance were higher in patients assessed late (all p
Published: 2021

18. Modeling the Cost Savings of Continuous Pulse Oximetry and Capnography Monitoring of United States General Care Floor Patients Receiving Opioids Based on the PRODIGY Trial

Author: Carla R. Jungquist, Wolfgang Buhre, Ashish Khanna, Roy Soto, Leif Saager, Fabio Di Piazza, MUMC+: Centrum voor Acute en Kritieke Zorg (3), Anesthesiologie, MUMC+: MA Anesthesiologie (9), and RS: MHeNs - R3 - Neuroscience
Subjects: medicine.medical_specialty, IMPACT, Healthcare economics, Cost savings, Continuous monitoring, Break-even analysis, Continuous pulse oximetry, Capnography, Humans, Medicine, Economic model, Pharmacology (medical), Oximetry, health care economics and organizations, Depression (differential diagnoses), General care floor, Monitoring, Physiologic, Original Research, INDUCED RESPIRATORY DEPRESSION, OUTCOMES, medicine.diagnostic_test, business.industry, General Medicine, RESCUE, United States, Pulse oximetry, Respiratory compromise, Respiratory depression, Analgesics, Opioid, Capnography monitoring, Emergency medicine, Cohort, ADVERSE EVENTS, business
Abstract: Introduction Despite the high incidence of respiratory depression on the general care floor and evidence that continuous monitoring improves patient outcomes, the cost–benefit of continuous pulse oximetry and capnography monitoring of general care floor patients remains unknown. This study modeled the cost and length of stay savings, investment break-even point, and likelihood of cost savings for continuous pulse oximetry and capnography monitoring of general care floor patients at risk for respiratory depression. Methods A decision tree model was created to compare intermittent pulse oximetry versus continuous pulse oximetry and capnography monitoring. The model utilized costs and outcomes from the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial, and was applied to a modeled cohort of 2447 patients receiving opioids per median-sized United States general care floor annually. Results Continuous pulse oximetry and capnography monitoring of high-risk patients is projected to reduce annual hospital cost by $535,531 and cumulative patient length of stay by 103 days. A 1.5% reduction in respiratory depression would achieve a break-even investment point and justify the investment cost. The probability of cost saving is ≥ 80% if respiratory depression is decreased by ≥ 17%. Expansion of continuous monitoring to high- and intermediate-risk patients, or to all patients, is projected to reach a break-even point when respiratory depression is reduced by 2.5% and 3.5%, respectively, with a ≥ 80% probability of cost savings when respiratory depression decreases by ≥ 27% and ≥ 31%, respectively. Conclusion Compared to intermittent pulse oximetry, continuous pulse oximetry and capnography monitoring of general care floor patients receiving opioids has a high chance of being cost-effective. Trial Registration www.clinicaltrials.gov, Registration ID: NCT02811302. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01779-7.
Published: 2021

19. Difficulty in Advancing Flexible Epidural Catheters When Establishing Labor Analgesia: An Observational Open-label Randomized Trial

Author: Leif Saager, Baskar Rajala, Shubhangi Singh, Ruth Cassidy, Jill M. Mhyre, Thomas T. Klumpner, David M. Eckmann, Virgil Manica, Carlo Pancaro, Milo Engoren, Christie Vahabzadeh, Timur Dubovoy, Jasmine Purtell, Sean P Maxwell, and Dana LaBuda
Subjects: Adult, medicine.medical_specialty, Catheters, Epidural needles, Tuohy needle, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Pregnancy, medicine, Humans, Labor analgesia, Prospective Studies, Prospective cohort study, Pliability, Analgesics, Labor, Obstetric, business.industry, Equipment Design, Surgery, Analgesia, Epidural, Catheter, Epidural catheter, Anesthesiology and Pain Medicine, Female, Open label, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND While flexible epidural catheters reduce the risk of paresthesia and intravascular cannulation, they may be more challenging to advance beyond the tip of a Tuohy needle. This may increase placement time, number of attempts, and possibly complications when establishing labor analgesia. This study investigated the ability to advance flexible epidural catheters through different epidural needles from 2 commonly used, commercially available, epidural kits. METHODS We hypothesized that the multiorifice wire-reinforced polyamide nylon blend epidural catheters will have a higher rate of successful first attempt insertion than the single-end hole wire-reinforced polyurethane catheters for the establishment of labor analgesia. The primary outcome was a difference in proportions of failure to advance the epidural catheter between the 2 epidural kits and was tested by a χ2 test. Two-hundred forty epidural kits were collected (n = 120/group) for 240 laboring patients requesting epidural analgesia in this open-label clinical trial from November 2018 to September 2019. Two-week time intervals were randomized for the exclusive use of 1 of the 2 kits in this study, where all patients received labor analgesia through either the flexible epidural catheter "A" or the flexible epidural catheter "B." Engineering properties of the equipment used were then determined. RESULTS Flexible epidural catheter "A," the single-end hole wire-reinforced polyurethane catheter, did not advance at the first attempt in 15% (n = 18 of 120) of the parturients compared to 0.8% (n = 1 of 120) of the catheter "B," the multiorifice wire-reinforced polyamide nylon blend epidural catheter (P < .0001). Twenty-five additional epidural needle manipulations were recorded in the laboring patients who received catheter "A," while 1 epidural needle manipulation was recorded in the parturients who received catheter "B" (P < .0001). Bending stiffness of the epidural catheters used from kit "B" was twice the bending stiffness of the catheters used from kit "A" (bending stiffness catheters "A" 0.64 ± 0.04 N·mm2 versus bending stiffness catheters "B" 1.28 ± 0.20 N·mm2, P = .0038), and the angle formed by the needle and the epidural catheter from kit "A" was less acute than the angle formed from kit "B" (kit "A" 14.17 ± 1.72° versus kit "B" 21.83 ± 1.33°, P = .0036), with a mean difference of 7.66° between the 2 kits' angles. CONCLUSIONS The incidence of an inability to advance single-end hole wire-reinforced polyurethane catheter was higher compared to the use of multiorifice wire-reinforced polyamide nylon blend epidural catheter. Variation of morphological features of epidural needles and catheters may play a critical role in determining the successful establishment of labor epidural analgesia.
Published: 2022

20. A Clinical and Budgetary Impact Analysis of Introducing Sugammadex for Routine Reversal of Neuromuscular Blockade in a Hypothetical Cohort in the US

Author: Lori D. Bash, Yiling Jiang, and Leif Saager
Subjects: Adult, 030213 general clinical medicine, Post-operative complications, Cost, Sugammadex, 03 medical and health sciences, 0302 clinical medicine, Bridion, Humans, Medicine, Pharmacology (medical), Rocuronium, health care economics and organizations, Original Research, Neuromuscular Blockade, business.industry, General Medicine, Budget impact, Neuromuscular Blocking Agents, Neostigmine, Blockade, 030220 oncology & carcinogenesis, Anesthesia, Cohort, business, Neuromuscular Nondepolarizing Agents, gamma-Cyclodextrins, medicine.drug
Abstract: Introduction Sugammadex rapidly reverses the effects of rocuronium- and vecuronium-induced neuromuscular blockade (NMB), offering a more complete and predictable NMB recovery than cholinesterase inhibitors. Despite clinical benefits, cost pressures on hospital budgets influence the choice of the NMB reversal method. This study evaluated clinical and healthcare system payer’s budget impacts associated with sugammadex in the US for routine reversal of moderate or deep rocuronium- or vecuronium-induced NMB in adults undergoing surgery. Methods A 1-year decision analytic model was constructed reflecting a set of procedures using rocuronium or vecuronium that resulted in moderate or deep NMB at the end of surgery. Two scenarios were considered for a hypothetical cohort of 100,000 patients: without sugammadex versus with sugammadex. Comparators included neostigmine (+glycopyrrolate) and no neuromuscular blocking agents (NMBAs). Total costs (in 2019 US dollars) to a healthcare system [net of costs of reversal agents and overall cost offsets via reduction in postoperative pulmonary complications (PPC)] were compared. Results A total of 9971 surgical procedures utilized rocuronium or vecuronium, resulting in moderate (91.0% of cases) or deep (9.0%) blockade at the end of surgeries. In the with sugammadex scenario, sugammadex replaced neostigmine in 4156 of 9585 procedures versus the without sugammadex scenario that used only neostigmine for NMB reversal. Introducing sugammadex reduced PPC events by 12% (58 cases) among the modeled procedures, leading to a budget impact of –$3,079,703 (–$309 per modeled procedure, or a 10.9% reduction in total costs). The results did not vary qualitatively in one-way sensitivity analyses. Conclusions The additional costs of sugammadex for the reversal of rocuronium- or vecuronium-induced NMB could be offset by improved outcomes (i.e., reduced PPC events), and potentially lead to overall healthcare budgetary savings versus reversal with neostigmine or spontaneous recovery. This study provides insights into savings that can be obtained beyond the anesthesia budget, reducing the broader clinical and budgetary burden on the hospital.
Published: 2021

21. Anatomic lung recruitment in the early phase of severe COVID-19-pneumonia

Author: Onnen Moerer, Stephani C, Konrad Meissner, Peter Herrmann, Leif Saager, Joachim Lotz, and Ritter Co
Subjects: Male, Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pulmonary Edema, Positive-Pressure Respiration, 03 medical and health sciences, Diseases of the respiratory system, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Letter to the Editor, Lung, Aged, Respiratory Distress Syndrome, RC705-779, business.industry, COVID-19, Organ Size, Middle Aged, medicine.disease, Lung recruitment, Pneumonia, 030228 respiratory system, Immunology, Tomography, X-Ray Computed, business, Early phase
Published: 2021

22. Elektrokonvulsionstherapie in der Schwangerschaft: Fallbericht und interdisziplinäre Behandlungsvorschläge

Author: Sebastian Horn, Leif Saager, David Zilles-Wegner, Sarah Trost, Mareike Ernst, and Karoline Walliser
Subjects: medicine.medical_specialty, medicine.medical_treatment, Effectiveness, 03 medical and health sciences, 0302 clinical medicine, Electroconvulsive therapy, Pregnancy, Humans, Medicine, Anesthesia, Electroconvulsive Therapy, Suggestion, Gynecology, Interdisciplinary treatment, Neonatologie, Geburtshilfe, business.industry, Übersichten, General Medicine, 030227 psychiatry, Sicherheit, Obstetrics, Psychiatry and Mental health, Psychotic Disorders, Neurology, Case-Control Studies, Female, Wirksamkeit, Neurology (clinical), Neonatology, Safety, business, 030217 neurology & neurosurgery, Anästhesie
Abstract: Psychiatric disorders during pregnancy are common. Electroconvulsive therapy (ECT) can be indicated in severely affective or psychotic disorders with the necessity of a rapid response. Currently available review articles greatly differ in the methodology, leading to divergent conclusions concerning the use of ECT during pregnancy.Description of a new clinical case and interdisciplinary treatment suggestions for the safe application of ECT in pregnancy.Clinical case report and selective review of the literature with special consideration of existing systematic reviews.This case report shows the potentially high effectiveness and safe administration of ECT in pregnancy for both mother and fetus. The undesired adverse events associated with ECT described in the literature are largely qualitatively congruent with the risks of severe psychotic disorders in pregnancy per se. For a better risk-benefit analysis, larger case control studies would be desirable. Under the premise of a thorough evaluation of the indications, good interdisciplinary coordination and consideration of the specific practical requirements, ECT is a useful therapeutic option in pregnancy.HINTERGRUND: Psychische Störungen in der Schwangerschaft sind häufig. Besonders bei schweren affektiven oder psychotischen Störungen mit Notwendigkeit eines raschen Ansprechens kann eine Elektrokonvulsionstherapie (EKT) indiziert sein. Dazu vorliegende Übersichtsartikel unterscheiden sich methodisch stark, was zu unterschiedlichen Schlussfolgerungen hinsichtlich der Anwendung der EKT bei Schwangerschaft führt.Darstellung eines neuen klinischen Falls sowie interdisziplinärer Behandlungsvorschläge zur sicheren Anwendung der EKT bei Schwangerschaft.Fallbericht und selektive Literaturübersicht unter besonderer Berücksichtigung der existierenden systematischen Reviews.Die aktuelle Kasuistik zeigt die potenziell hohe Wirksamkeit sowie die für Mutter und Fetus sichere Anwendung der EKT während der Schwangerschaft. Die in der Literatur beschriebenen unerwünschten Ereignisse entsprechen qualitativ weitgehend den Risiken bei schwerer psychischer Störung in der Schwangerschaft. Zur besseren Nutzen-Risiko-Abwägung wären größere Fall-Kontroll-Studien wünschenswert. Bei sorgfältiger Indikationsstellung, guter interdisziplinärer Abstimmung und Beachtung der Besonderheiten in der praktischen Durchführung ist die EKT auch in der Schwangerschaft eine sinnvolle Behandlungsoption.
Published: 2020

23. Sugammadex versus Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER)

Author: Michael R. Mathis, Michelle T. Vaughn, Timur Dubovoy, Leif Saager, Karsten Bartels, Amit Bardia, Amy Shanks, Roy G. Soto, Sachin Kheterpal, Patrick J. McCormick, Robert B. Schonberger, Lori D. Bash, Nirav Shah, and Douglas A. Colquhoun
Subjects: Neuromuscular Blockade, Adult patients, business.industry, Pulmonary Complication, medicine.disease, Sugammadex, 3. Good health, Neostigmine, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, Anesthesiology and Pain Medicine, Matched cohort, 030202 anesthesiology, Anesthesia, medicine, business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract: Background Five percent of adult patients undergoing noncardiac inpatient surgery experience a major pulmonary complication. The authors hypothesized that the choice of neuromuscular blockade reversal (neostigmine vs. sugammadex) may be associated with a lower incidence of major pulmonary complications. Methods Twelve U.S. Multicenter Perioperative Outcomes Group hospitals were included in a multicenter observational matched-cohort study of surgical cases between January 2014 and August 2018. Adult patients undergoing elective inpatient noncardiac surgical procedures with general anesthesia and endotracheal intubation receiving a nondepolarizing neuromuscular blockade agent and reversal were included. Exact matching criteria included institution, sex, age, comorbidities, obesity, surgical procedure type, and neuromuscular blockade agent (rocuronium vs. vecuronium). Other preoperative and intraoperative factors were compared and adjusted in the case of residual imbalance. The composite primary outcome was major postoperative pulmonary complications, defined as pneumonia, respiratory failure, or other pulmonary complications (including pneumonitis; pulmonary congestion; iatrogenic pulmonary embolism, infarction, or pneumothorax). Secondary outcomes focused on the components of pneumonia and respiratory failure. Results Of 30,026 patients receiving sugammadex, 22,856 were matched to 22,856 patients receiving neostigmine. Out of 45,712 patients studied, 1,892 (4.1%) were diagnosed with the composite primary outcome (3.5% sugammadex vs. 4.8% neostigmine). A total of 796 (1.7%) patients had pneumonia (1.3% vs. 2.2%), and 582 (1.3%) respiratory failure (0.8% vs. 1.7%). In multivariable analysis, sugammadex administration was associated with a 30% reduced risk of pulmonary complications (adjusted odds ratio, 0.70; 95% CI, 0.63 to 0.77), 47% reduced risk of pneumonia (adjusted odds ratio, 0.53; 95% CI, 0.44 to 0.62), and 55% reduced risk of respiratory failure (adjusted odds ratio, 0.45; 95% CI, 0.37 to 0.56), compared to neostigmine. Conclusions Among a generalizable cohort of adult patients undergoing inpatient surgery at U.S. hospitals, the use of sugammadex was associated with a clinically and statistically significant lower incidence of major pulmonary complications. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2020

24. Multicenter Perioperative Outcomes Group Enhanced Observation Study Postoperative Pain Profiles, Analgesic Use, and Transition to Chronic Pain and Excessive and Prolonged Opioid Use Patterns Methodology

Author: Nathan L. Pace, Karen L. Posner, Salome B Alpert, Ami R. Stuart, Anik Sinha, Karen B. Domino, Marcel E. Durieux, Chad M. Brummett, Leif Saager, Kai Kuck, Sachin Kheterpal, and Bhiken I. Naik
Subjects: medicine.medical_specialty, Postoperative pain, Analgesic, MEDLINE, Anxiety, Article, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Surveys and Questionnaires, medicine, Humans, Pain Management, Postoperative Period, Prospective Studies, Prospective cohort study, Case report form, Pain Measurement, Analgesics, Pain, Postoperative, Depression, business.industry, Chronic pain, Perioperative, Opioid-Related Disorders, medicine.disease, 3. Good health, Analgesics, Opioid, Treatment Outcome, Anesthesiology and Pain Medicine, Physical therapy, Observational study, Self Report, Chronic Pain, business, 030217 neurology & neurosurgery
Abstract: In order to study the impact of anesthesia opioid-related outcomes and acute and chronic post-surgical pain, we organized a multi-center study that comprehensively combined detailed perioperative data elements from multiple institutions. By combining pre- and post-operative patient reported outcomes with automatically extracted high resolution intra-operative data obtained through the Multicenter Perioperative Outcomes Group (MPOG), the authors sought to describe the impact of patient characteristics, pre-operative psychological factors, surgical procedure, anesthetic course, post-operative pain management, and post-discharge pain management on post-discharge pain profiles and opioid consumption patterns. This study is unique in that it utilized multi-center prospective data collection using a digital case report form integrated with the MPOG framework and database. Therefore, the study serves as a model for future studies using this innovative method. Full results will be reported in future papers; the purpose of this paper is to describe the methods of this study.
Published: 2020

25. Considerations for Integration of Perioperative Electronic Health Records Across Institutions for Research and Quality Improvement

Author: Michael F. Aziz, Michael R. Mathis, Michelle T. Vaughn, Nirav Shah, Douglas A. Colquhoun, Kevin K. Tremper, Michael L. Burns, Robert E. Freundlich, Amy Shanks, Kathryn Buehler, Sachin Kheterpal, Steven R. Kapeles, and Leif Saager
Subjects: Biomedical Research, Source data, Knowledge management, Quality management, business.industry, Standardized approach, MEDLINE, Perioperative, Data structure, Quality Improvement, Perioperative Care, Article, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, Data integrity, Data quality, Outcome Assessment, Health Care, Electronic Health Records, Humans, Multicenter Studies as Topic, Medicine, business, 030217 neurology & neurosurgery
Abstract: Use of the electronic health record (EHR) has become a routine part of perioperative care in the United States. Secondary use of EHR data includes research, quality, and educational initiatives. Fundamental to secondary use is a framework to ensure fidelity, transparency, and completeness of the source data. In developing this framework, competing priorities must be considered as to which data sources are used and how data are organized and incorporated into a useable format. In assembling perioperative data from diverse institutions across the United States and Europe, the Multicenter Perioperative Outcomes Group (MPOG) has developed methods to support such a framework. This special article outlines how MPOG has approached considerations of data structure, validation, and accessibility to support multicenter integration of perioperative EHRs. In this multicenter practice registry, MPOG has developed processes to extract data from the perioperative EHR; transform data into a standardized format; and validate, deidentify, and transfer data to a secure central Coordinating Center database. Participating institutions may obtain access to this central database, governed by quality and research committees, to inform clinical practice and contribute to the scientific and clinical communities. Through a rigorous and standardized approach to ensure data integrity, MPOG enables data to be usable for quality improvement and advancing scientific knowledge. As of March 2019, our collaboration of 46 hospitals has accrued 10.7 million anesthesia records with associated perioperative EHR data across heterogeneous vendors. Facilitated by MPOG, each site retains access to a local repository containing all site-specific perioperative data, distinct from source EHRs and readily available for local research, quality, and educational initiatives. Through committee approval processes, investigators at participating sites may additionally access multicenter data for similar initiatives. Emerging from this work are 4 considerations that our group has prioritized to improve data quality: (1) data should be available at the local level before Coordinating Center transfer; (2) data should be rigorously validated against standardized metrics before use; (3) data should be curated into computable phenotypes that are easily accessible; and (4) data should be collected for both research and quality improvement purposes because these complementary goals bolster the strength of each endeavor.
Published: 2020

26. Classification of Current Procedural Terminology Codes from Electronic Health Record Data Using Machine Learning

Author: Bo Lu, John C. Vandervest, Leif Saager, Douglas A. Colquhoun, Michael R. Mathis, Michael L. Burns, Sachin Kheterpal, Xinyu Tan, and Nirav Shah
Subjects: Adult, Male, Current Procedural Terminology, Matching (statistics), Quality management, Adolescent, Databases, Factual, Machine learning, computer.software_genre, Article, Machine Learning, Young Adult, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Feature (machine learning), Electronic Health Records, Humans, Medicine, 030212 general & internal medicine, Child, Artificial neural network, business.industry, Procedure code, Middle Aged, Support vector machine, Statistical classification, Anesthesiology and Pain Medicine, Child, Preschool, Female, Neural Networks, Computer, Artificial intelligence, business, computer
Abstract: Background Accurate anesthesiology procedure code data are essential to quality improvement, research, and reimbursement tasks within anesthesiology practices. Advanced data science techniques, including machine learning and natural language processing, offer opportunities to develop classification tools for Current Procedural Terminology codes across anesthesia procedures. Methods Models were created using a Train/Test dataset including 1,164,343 procedures from 16 academic and private hospitals. Five supervised machine learning models were created to classify anesthesiology Current Procedural Terminology codes, with accuracy defined as first choice classification matching the institutional-assigned code existing in the perioperative database. The two best performing models were further refined and tested on a Holdout dataset from a single institution distinct from Train/Test. A tunable confidence parameter was created to identify cases for which models were highly accurate, with the goal of at least 95% accuracy, above the reported 2018 Centers for Medicare and Medicaid Services (Baltimore, Maryland) fee-for-service accuracy. Actual submitted claim data from billing specialists were used as a reference standard. Results Support vector machine and neural network label-embedding attentive models were the best performing models, respectively, demonstrating overall accuracies of 87.9% and 84.2% (single best code), and 96.8% and 94.0% (within top three). Classification accuracy was 96.4% in 47.0% of cases using support vector machine and 94.4% in 62.2% of cases using label-embedding attentive model within the Train/Test dataset. In the Holdout dataset, respective classification accuracies were 93.1% in 58.0% of cases and 95.0% among 62.0%. The most important feature in model training was procedure text. Conclusions Through application of machine learning and natural language processing techniques, highly accurate real-time models were created for anesthesiology Current Procedural Terminology code classification. The increased processing speed and a priori targeted accuracy of this classification approach may provide performance optimization and cost reduction for quality improvement, research, and reimbursement tasks reliant on anesthesiology procedure codes. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2020

27. Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury

Author: Leif Saager, Fabian O. Kooij, Allison M. Janda, Bhiken I. Naik, Michael L. Burns, Janet Wilczak, Amy Shanks, Steven Lins, Simon Tom, Robert M. Craft, Terri A. Ellis, W. P. Peterson, Warren J. Levy, Marcel E. Durieux, Christopher Wedeven, Robert E. Freundlich, Kenneth C. Cummings, Joshua Berris, Mitchell F. Berman, Scott A. Miller, Peter G. Coles, Leslie C. Jameson, Roy G. Soto, Daniel L. Helsten, Peter M. Fleishut, Jonathan P. Wanderer, William C. Paganelli, Govind Rangrass, Sachin Kheterpal, Daniel A. Biggs, Bala G. Nair, Traci Coffman, Kevin K. Tremper, Minjae Kim, Michael F. Aziz, John E. LaGorio, Michael R. Mathis, Michael Heung, Susan Molina, Douglas A. Colquhoun, Wilton A. van Klei, Milo Engoren, Robert B. Schonberger, Anesthesiology, and Other Research
Subjects: Adult, Male, Mean arterial pressure, Adolescent, Renal function, Risk Assessment, Article, Cohort Studies, Young Adult, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, 030202 anesthesiology, Journal Article, Humans, Medicine, Arterial Pressure, Risk factor, Intraoperative Complications, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Acute kidney injury, Anemia, Retrospective cohort study, Odds ratio, Acute Kidney Injury, Middle Aged, medicine.disease, Treatment Outcome, Anesthesiology and Pain Medicine, Blood pressure, Anesthesia, Preoperative Period, Female, Hypotension, Risk assessment, business, 030217 neurology & neurosurgery
Abstract: BackgroundDespite the significant healthcare impact of acute kidney injury, little is known regarding prevention. Single-center data have implicated hypotension in developing postoperative acute kidney injury. The generalizability of this finding and the interaction between hypotension and baseline patient disease burden remain unknown. The authors sought to determine whether the association between intraoperative hypotension and acute kidney injury varies by preoperative risk.MethodsMajor noncardiac surgical procedures performed on adult patients across eight hospitals between 2008 and 2015 were reviewed. Derivation and validation cohorts were used, and cases were stratified into preoperative risk quartiles based upon comorbidities and surgical procedure. After preoperative risk stratification, associations between intraoperative hypotension and acute kidney injury were analyzed. Hypotension was defined as the lowest mean arterial pressure range achieved for more than 10 min; ranges were defined as absolute (mmHg) or relative (percentage of decrease from baseline).ResultsAmong 138,021 cases reviewed, 12,431 (9.0%) developed postoperative acute kidney injury. Major risk factors included anemia, estimated glomerular filtration rate, surgery type, American Society of Anesthesiologists Physical Status, and expected anesthesia duration. Using such factors and others for risk stratification, patients with low baseline risk demonstrated no associations between intraoperative hypotension and acute kidney injury. Patients with medium risk demonstrated associations between severe-range intraoperative hypotension (mean arterial pressure less than 50 mmHg) and acute kidney injury (adjusted odds ratio, 2.62; 95% CI, 1.65 to 4.16 in validation cohort). In patients with the highest risk, mild hypotension ranges (mean arterial pressure 55 to 59 mmHg) were associated with acute kidney injury (adjusted odds ratio, 1.34; 95% CI, 1.16 to 1.56). Compared with absolute hypotension, relative hypotension demonstrated weak associations with acute kidney injury not replicable in the validation cohort.ConclusionsAdult patients undergoing noncardiac surgery demonstrate varying associations with distinct levels of hypotension when stratified by preoperative risk factors. Specific levels of absolute hypotension, but not relative hypotension, are an important independent risk factor for acute kidney injury.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New
Published: 2020

28. Lung Ultrasound and Electrical Impedance Tomography During Ventilator-Induced Lung Injury

Author: Irene Steinberg, Iacopo Pasticci, Mattia Busana, Andrea Costamagna, Günter Hahn, Simone Gattarello, Paola Palermo, Stefano Lazzari, Federica Romitti, Peter Herrmann, Onnen Moerer, Leif Saager, Konrad Meissner, Michael Quintel, and Luciano Gattinoni
Subjects: Positive-Pressure Respiration, Swine, Ventilator-Induced Lung Injury, Electric Impedance, Tidal Volume, Animals, Humans, Female, Lung Injury, Critical Care and Intensive Care Medicine, Tomography, X-Ray Computed, Lung
Abstract: Lung damage during mechanical ventilation involves lung volume and alveolar water content, and lung ultrasound (LUS) and electrical impedance tomography changes are related to these variables. We investigated whether these techniques may detect any signal modification during the development of ventilator-induced lung injury (VILI).Experimental animal study.Experimental Department of a University Hospital.Forty-two female pigs (24.2 ± 2.0 kg).The animals were randomized into three groups (n = 14): high tidal volume (TV) (mean TV, 803.0 ± 121.7 mL), high respiratory rate (RR) (mean RR, 40.3 ± 1.1 beats/min), and high positive-end-expiratory pressure (PEEP) (mean PEEP, 24.0 ± 1.1 cm H2O). The study lasted 48 hours. At baseline and at 30 minutes, and subsequently every 6 hours, we recorded extravascular lung water, end-expiratory lung volume, lung strain, respiratory mechanics, hemodynamics, and gas exchange. At the same time-point, end-expiratory impedance was recorded relatively to the baseline. LUS was assessed every 12 hours in 12 fields, each scoring from 0 (presence of A-lines) to 3 (consolidation).In a multiple regression model, the ratio between extravascular lung water and end-expiratory lung volume was significantly associated with the LUS total score (p0.002; adjusted R2, 0.21). The variables independently associated with the end-expiratory difference in lung impedance were lung strain (p0.001; adjusted R2, 0.18) and extravascular lung water (p0.001; adjusted R2, 0.11).Data suggest as follows. First, what determines the LUS score is the ratio between water and gas and not water alone. Therefore, caution is needed when an improvement of LUS score follows a variation of the lung gas content, as after a PEEP increase. Second, what determines the end-expiratory difference in lung impedance is the strain level that may disrupt the intercellular junction, therefore altering lung impedance. In addition, the increase in extravascular lung water during VILI development contributed to the observed decrease in impedance.
Published: 2022

29. Incidence of sedation-related adverse events during ERCP with anesthesia assistance: a multicenter observational study

Author: Linda C. Cummings, Chen Liang, Edward J. Mascha, Leif Saager, Zachary L. Smith, Sekar Bhavani, John J. Vargo, and Kenneth C. Cummings
Subjects: Adult, Cholangiopancreatography, Endoscopic Retrograde, Incidence, Gastroenterology, Humans, Radiology, Nuclear Medicine and imaging, Anesthesia, General, Hypotension, Hypoxia, Retrospective Studies
Abstract: Anesthesia assistance is commonly used for ERCP. General anesthesia (GA) may provide greater airway protection but may lead to hypotension. We aimed to compare GA versus sedation without planned intubation (SWPI) on the incidence of hypoxemia and hypotension. We also explored risk factors for conversion from SWPI to GA.This observational study used data from the Multicenter Perioperative Outcomes Group. Adults with American Society of Anesthesiologists physical status class I to IV undergoing ERCP between 2006 and 2019 were included. We compared GA and SWPI on incidence of hypoxemia (oxygen saturation 90% for ≥3 minutes) and hypotension (mean arterial pressure 65 mm Hg for ≥5 minutes) using joint hypothesis testing. The association between anesthetic approach and outcomes was assessed using logistic regression. The noninferiority delta for hypoxemia and hypotension was an odds ratio of 1.20. One approach was deemed better if it was noninferior on both outcomes and superior on at least 1 outcome. To explore risk factors associated with conversion from SWPI to GA, we constructed a logistic regression model.Among 61,735 cases from 42 institutions, 38,830 (63%) received GA and 22,905 (37%) received SWPI. The GA group had 1.27 times (97.5% confidence interval, 1.19-1.35) higher odds of hypotension but .71 times (97.5% confidence interval, .63-.80) lower odds of hypoxemia. Neither group was noninferior to the other on both outcomes. Conversion from SWPI to GA occurred in 6.5% of cases and was associated with baseline comorbidities and higher institutional procedure volume.GA for ERCP was associated with less hypoxemia, whereas SWPI was associated with less hypotension. Neither approach was better on the combined incidence of hypotension and hypoxemia.
Published: 2022

30. Association of Anesthesiologist Staffing Ratio With Surgical Patient Morbidity and Mortality

Author: Michael L, Burns, Leif, Saager, Ruth B, Cassidy, Graciela, Mentz, George A, Mashour, and Sachin, Kheterpal
Subjects: Adult, Cohort Studies, Male, Postoperative Complications, Adolescent, Workforce, Humans, Female, Surgery, Middle Aged, Morbidity, Anesthesiologists, Retrospective Studies
Abstract: Recent studies have investigated the effect of overlapping surgeon responsibilities or nurse to patient staffing ratios on patient outcomes, but the association of overlapping anesthesiologist responsibilities with patient outcomes remains unexplored to our knowledge.To examine the association between different levels of anesthesiologist staffing ratios and surgical patient morbidity and mortality.A retrospective, matched cohort study consisting of major noncardiac inpatient surgical procedures performed from January 1, 2010, to October 31, 2017, was conducted in 23 US academic and private hospitals. A total of 866 453 adult patients (aged ≥18 years) undergoing major inpatient surgery within the Multicenter Perioperative Outcomes Group electronic health record registry were included. Anesthesiologist sign-in and sign-out times were used to calculate a continuous time-weighted average staffing ratio variable for each operation. Propensity score-matching methods were applied to create balanced sample groups with respect to patient-, operative-, and hospital-level confounders and resulted in 4 groups based on anesthesiologist staffing ratio. Groups consisted of patients receiving care from an anesthesiologist covering 1 operation (group 1), more than 1 to no more than 2 overlapping operations (group 1-2), more than 2 to no more than 3 overlapping operations (group 2-3), and more than 3 to no more than 4 overlapping operations (group 3-4). Data analysis was performed from October 2019 to October 2021.Undergoing a major inpatient surgical operation that involved an anesthesiologist providing care for up to 4 overlapping operations.The primary composite outcome was 30-day mortality and 6 major surgical morbidities (cardiac, respiratory, gastrointestinal, urinary, bleeding, and infectious complications) derived from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision discharge diagnosis codes.In all, 578 815 adult patients (mean [SD] age, 55.7 [16.2] years; 55.1% female) were analyzed. After matching operations according to anesthesiologist staffing ratio, 48 555 patients were in group 1; 247 057, group 1-2; 216 193, group 2-3; and 67 010, group 3-4. Increasing anesthesiologist coverage responsibilities was associated with an increase in risk-adjusted surgical patient morbidity and mortality. Compared with patients in group 1-2, those in group 2-3 had a 4% relative increase in risk-adjusted mortality and morbidity (5.06% vs 5.25%; adjusted odds ratio [AOR], 1.04; 95% CI, 1.01-1.08; P = .02) and those in group 3-4 had a 14% increase in risk-adjusted mortality and morbidity (5.06% vs 5.75%; AOR, 1.15; 95% CI, 1.09-1.21; P .001).This study's findings suggest that increasing overlapping coverage by anesthesiologists is associated with increased surgical patient morbidity and mortality. Therefore, the potential effects of staffing ratios in perioperative team models should be considered in clinical coverage efforts.
Published: 2022

31. Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Author: Labeau, Sonia O, Afonso, Elsa, Benbenishty, Julie, Blackwood, Bronagh, Boulanger, Carole, Brett, Stephen J, Calvino-Gunther, Silvia, Chaboyer, Wendy, Coyer, Fiona, Deschepper, Mieke, François, Guy, Honore, Patrick M, Jankovic, Radmilo, Khanna, Ashish K, Llaurado-Serra, Mireia, Lin, Frances, Rose, Louise, Rubulotta, Francesca, Saager, Leif, Williams, Ged, Blot, Stijn I, Dritan, Muzha, Antoni Margarit Ribas, Fernando, Lipovesty, Cecilia, Loudet, Fiona, Coyer, Philipp, Eller, Nafseen, Mostafa, Patrick, M Honoré, Vanesa Mercado Telleria, Jasmina, Smajic, Paula Cristina Nogueira, Khalid Mahmood Khan Nafees, Romuald, Hentchoya, Louise, Rose, Javiera, Soledad, Frances, Lin, Yenny, Cardenas, Amylkar Garay Reyes, Alan, Sustic, Meropi, Mpouzika, Tamas, Vymazal, Hanne Irene Jensen, Hernan, Aguirre-Bermeo, Liivi, Maddison, Maija, Valta, Silvia, Calvino-Gunther, Frank, Bloos, Faustina Excel Adipa, Vasilios, Koulouras, Judy, Enamorado, Zsuzsann, Ágoston, Hrönn, Birgisdóttir, Amit, Gupta, Mohan, Gurjar, Bram, Kilapong, Seyed Mohammadreza Hashemian, Ignacio, Martin-Loeches, Julie, Benbenishty, Andrea, Cortegiani, Kelly, Fletcher, Yoshiro, Hayashi, Wangari, Waweru-Siika, Khalid, Abidi, Sang-Min, Lee, Burhan, Hadri, Mihails, Dolgusevs, Fayez François Abillama, Tomas, Jovaisa, Cyril, Thix, Muhammed, Elhadi, Basri Mat Nor, Shanti, Ratnam, Mohd Zulfakar Mazlan, Sundaresan, Maiyalagan, Luis, Sánchez-Hurtado, Adrian, Belii, Mendsaikhan, Naranpurev, Prabha, Gautam, Dylan De Lange, Rachael, Parke, Rose Ekama Ilesanmi, Mirjana, Shosholcheva, Antonija, Petosic, Ranveig, Lind, Madiha Hashmi Ffarcsi, Javier, Bogarin, Aaron Mark Hernandez, Malgorzata, Mikaszewska-Sokolewicz, Bruno, Sousa, Dana, Tomescu, Dorel, Sandesc, Theogene, Twagirumugabe, Vitaly, Gusarov, Maie, Ebaid, Radmilo, Jankovic, Gari, Slobodianiuk, Andrea, Martonova, Rihard, Knafelj, Mervyn, Mer, Emilio, Maseda, Bernardo, Panka, Joerg, C Schefold, Eva, Joelsson-Alm, Konlawij, Trongtrakul, Lorna, Merritt-Charles, Lamia Ouanes Besbes, Yalım, Dikmen, Lesia, Zgrzheblovska, Mark, Fielding, Francesca, Rubulotta, Ashish, K Khanna, Leif, Saager, Ingrid von der Osten, Alban, Greca, Alma, Cani, Nordian, Xhindi, Genci, Hyska, Antonio Margarit Ribas, Susana, Pinto, Paulo, Alves, Romina, Esposito, Emanuel, Valgolio, John Thomas Sanchez Minope, Antonio, Abdala, Maria, Ayala, Silvina, Bravo, Ana, Bantar, Patricia, Delgado, Gustavo, Badariotti, Fernando, Lipovestky, Ana, Diaz, Pablo, Saul, Mariano, Setten, Alejandra, Aucapina, Ysica, Acosta, Victor, Gonzalez, Luis, Camputaro, Fernando, Baccaro, Robert, Villa, Marcela, Mastantuono, Emiliano, Dean, Oscar Fernández Rostello, Patricia, Brizuela, Julio Ricardo Bartoli, Matias, Guereschi, Cristian, Quiroga, Sofia, Putruele, Paula, Villegas, Veronica, Curilen, Ruben, Fernandez, Mariangeles Gabriela Nocheretti, Rosana Gabriela Escalante, Cecilia Inés Loudet, Silvia, Fernandez, Ana Laura Gonzalez, Gustavo Andres Alvarez, Federico, Iglesias, Silvia, Chaparro, Graciela, Zakalik, Gonzalo, Pagella, Matías, Baini, Pierina Arias Campos, Ignacio, Sabbag, Armando, Schmukler, Imelda Perdomo Fonseca, Gonzalo Martín Alvarez, Mario, Ramirez, Fernando, Tapia, Carlos Alejandro Bascary, Graciela Del Valle Gimenez, Fernando Pablo Bertoletti, Esteban, Milioto, Pablo Julio Maldonaldo Bonsignore, Maria Alejandra Fernandez, Julie, Smith, Tim, Chimunda, Lorraine, Thompson, Teena, Maguire, Wendy, Chaboyer, Stacey, Watts, Marion, Mitchell, Madeleine, Powell, India, Lye, Leanne, Parsons, Nerilee, Baker, Claire, Reynolds, Amy, Thompson, Kristy, Masters, Kellie, Sosnowski, Lynette, Morrison, Gavin, D Leslie, Ramanathan, Lakshmanan, Alexis, Tabah, Wendy, Brown, Sharon, McDowell-Skaines, Andrea, Mclucas, Chris, Smith, Mandy, Tallot, Sarah, Jones, Michelle, Barakat-Johnson, Thomas, Leong, Rand, Butcher, Kerrie, Martin, Philipp, Douschan, Dirk von Lewinski, René, Schmutz, Uta, Kolussi, Fatema, Salman, Zainab, Ateya, Koen De Decker, Niels Van Regenmortel, Anita, Jans, Patricia, Wijnands, Stefano, Coremans, Patrick, M Honore, David De Bels, Tanja, Depuydt, Caroline, Paillet, Luc-Marie, Jacquet, Walter, Swinnen, Francis, Hannes, Matthia, Mergeay, Stijn Van de Velde, Silvie, Allaert, Pieter, Hoste, Christophe, Borin, Sandrine, Balon, Vincent, Fraipont, Patrick, Biston, Nicolas De Schryver, Thierry, Dugernier, Ilse Van Cotthem, Angelica Olivetto de Almeida, Silvia Angelica Jorge, Delmiro, Becker, Raysa Cristina Schmidt, Evellyn, Oliveira, Aline, Ramalho, Eliane, Mazocoli, Audrey, Fioretti, Elaine, Barros, Leticia, Serpa, Suzana, Bianchini, Ticiane, Campanili, Taís, Pantaleao, Paulo Carlos Garcia, Ana Lucia Vitti Ronchini, Rayanne, Santos, Nurulhuda Binti, A Manap, Sean, Bagshaw, Dominic, Carney, Jon, Davidow, Ella, Rokosh, Andréa Maria Laizner, Samantha, Smith, Megan, Mcquirter, Betty Star Kampayana, René, Favre, Martin, Sills, Julie, Dallaire, Cathy, Becker, Sherissa, Microys, Bonnie, Bowes, Jennifer, Lajeunesse, Rishi, Ghosh, Jacqueline, Baptiste-Savoie, Rose, Raizman, Gabriel, Suen, Noushin, Taghavi, Orla, Smith, Clare, Fielding, Julieta, Canales, Pia, Molina, Javiera, Chaparro, Maria Idalia Sepulveda, Matias Jesús Flamm Zamorano, Pamela, Rocha, Ximena, Villanueva, Paola, Araya, Meneses, Dayan, Fernando, Avalos, Xiaohan, Li, Liu, Yu, Xinxia, Li, Xiaoyan, Chen, Zhixia, Jiang, Jing, Yang, Jingfang, Chen, Lei, Yang, Kefang, Wang, Jie, Gao, Xiuhua, Fang, Ronghua, Zhao, Xinhua, Xia, Hongmei, Liu, Jing, Li, Haiyan, Wang, Gen, Meng, Yanhong, Di, Damei, Wang, Rong Hua Zhao, Li Ping Hu, Peipei, Xu, Qing Feng Jiao, Hai Yun Wang, Chun Jie Xia, Yan, Liu, Mei, Ye, Yan, Wan, Wenmei, Wang, Yajun, Ding, Aiua, Ren, Yan, Gao, Qi, Li, Guifang, Du, Yanling, Shen, Yanming, Ding, Ning, Li, Cui, Yuan, Lei, Tan, Qiang, Lin, Hailing, Guo, Howe, Yan, Xiao, Xu, Wei, Zhang, Jinxian, Liang, Libing, Zhang, Eryun, Tian, Qian, Zhao, Lin, Insu, Jingwen, Dong, Yanmei, Gu, Ying, Liu, Lina, Zhao, Wei, Wang, Hongmei, Qiao, Lili, Tuo, Mengmeng, Lv, Jin Yu Zhu, Jifen, Zhu, Ying, Wei, Man, Liu, Yin, He, Jiyin, Cheng, Jin, Liu, Jia, Na, Dongfang, Wei, Qing, Li, Xiaoying, Wu, Huan, Duan, Dongliang, Lin, Qiong, Liang, Xiaofang, Luo, Yunfeng, Xiong, Rong Fen Huang, Jing, Fu, Tao, Zan, Man, Ye, Zeya, Shi, Yanfei, Long, Yang, Lei, Xiaodi, Liu, Chen, Yumei, Lingling, Wang, Yali, Zhang, Yan, Xu, Cheng, Wang, Zhijuan, Chengxia, Sun, Jinhui, Song, Yingli, Wang, Xiumei, Liu, Yupeng, Liu, Yuxia, Yuan, Qingping, Huang, Fengling, Yang, Yun, Wu, Xianping, Luo, Xiaowu, Bai, Hong, Zheng, Min, Song, Yue, Sun, Zhangshuangzi, Li, Feifei, Luo, Miao, Liu, Li Chuntang Li, Xinjian, Li, Guiping, Zhang, Lina, Xiao, Tingting, Yu, Guangyuan, Gao, Wei, Wei, Fanglan, Wang, Ting, Han, Tingting, Li, Zeng, Qi, Jing Mei Zeng, Yan, Long, Fuqun, Pan, Jing, Wang, Guoxue, He, Haiyan, Chen, Feifei, Zhang, Chao, Yu, Gao, Chunhua, Xiuying, Yao, Dongmei, Bai, Liu, Lu, Xuelian, Xu, Yan, Wang, Xuejuan, Liang, Zhang, Na, Aizhi, Zhang, Xiaochun, Hu, Hui, Zhang, Ruixia, Wang, Poon Shing Tak, Sung Wai Ho, Qun Xia Jiang, Xinran, Ding, Liu, Hong, Limei, Miao, Zhaoxia, Feng, Liping, Huang, Juan, Wu, Yuping, Wang, Jiye, Guo, Baoke, Zhang, Chaoqun, Ma, Han, Yu, Congcong, Liu, Min, Ding, Linlin, Luan, Jing, Zheng, Shanshan, Lv, Shumin, Jiang, Wenzhen, Cao, Xiujuan, Xue, Guangyan, Liu, Xiyan, Wei, Youru, Jiang, Zhiru, Yao, Gao, Li, Jinhua, Li, Wenwen, Zhao, Mei, Jiang, Junping, Hao, Jing, Zhang, Caiju, Song, Feifei, Chen, Shuhui, Wang, Lili, Hu, Deyan, Cao, Jianhong, Wan, Xiaomin, Wang, Hongyan, Shao, Zhenxia, Zhang, Xia, Cui, Jingyu, Liu, Lijuan, Zhao, Xingguo, Li, Limei, Fan, Ling, Zhang, Min, Yu, Biyan, Li, Chunxia, Li, Ling, Liu, Xuelian, Liu, Wenmin, Chen, Yan, Li, Zhang, Zhigang, Yuchen, Wu, Chenghau, Mu, Guoyan, Zhu, Fan, Yang, Qi, Bo, Ling, Li, Meili, Chen, Jing Hua Jiang, Hai, Yin, Xuelian, Pang, Yue Ying Gong, Shunzhu, Yang, Xiaoli, Yan, Xianhong, Zheng, Dehong, Lei, Lei, Lei, Yinhua, Guo, Lihong, Liu, Jing, Yu, Wei, Sun, Aiping, Bi, Weiwei, Li, Yang, Wu, Ji, Li, Dongshu, Ni, Zijing, Wu, Bing, Song, Qin, Fei, Yang, Xiaoyan, Qiong, Ran, Xixi, Li, Xueping, Jiao, Hua, Ji, Sun, Zhiping, Hong, Ma, Jianhong, Mu, Yanhua, Hao, Yin, Li, Ying, Wang, Caihong, Hui, Wenjie, Ju, Yuxia, Huo, Yuxia, Wang, Lei, Chen, Yan, Yan, Qingli, Zhao, Hongjuan, Chen, Guijun, Bao, Ying, Cao, Hong, Li, Hong, Zhang, Ying, Zhang, Lina, Xu, Jia, Guixiang, Ying, Li, Hui Min Zhao, Xia, Huang, Zhaoxing, Dai, Yanman, Jian, Hongsu, Zhang, Zhixia, Tian, Zu Qing Cao, Miao, Li, Yang, Liu, Fei, Ouyang, Fuying, Ma, Wangyan, Jin, Liuyan, Ge, Shifen, Wu, Weilian, Yuan, Tianfei, Chen, Guanxiu, Shi, Zhihong, Chen, Kewei, Liu, Xue, Lin, Yuemen, Ly, Sun, Lijuan, Xiao Fang Tian, Shuo, Wang, Zhangxia, Feng, Xiaozhe, Liu, Yunchun, Dong, Jundi, Zhang, Nie, Bocui, Guoxian, Wang, Yingjuan, Zhao, Xiaojun, Wu, Qiao, Yang, Rongjun Ling Hu, Xue Qin Li, Zhu Jun Yu, Yanlan, Yao, Xiaoqiong, Deng, Yan, Xiao, Yan, Xie, Yanping, Yang, Huai, Yang, Yuming, Zhou, Zhuqing, Li, Min, Xiao, Yongxia, Yang, Yani, Tian, Luz Marina Silva Gama, Juan Sebastian Hernandez, Nestor, Caicedo, Jorge, Marin, Maria-Elena, Ochoa, Monica, Gomez, José, Rojas-Suarez, Jeniffer, Gonzalez, Amylkar José Garay Reyes, Edwin, Chapeta, Estefania, Orozco, Ina, Filipović-Grčić, Anita, Vuković, Suzana, Pečenković, Aleksandar, Šuput, Gordana, Zivanovic-Posilovic, Armanda, Bozena, Nikolina, Udiljak, Morena, Milic, Renata Curic Radivojevic, Slobodan, Mihaljevic, Marijana, Matas, Dinko, Tonkovic, Hemena, Čuljak, Ivana, Herceg, Gordana, Pavlisa, Milena, Dobric, Tatjana, Beker, Višnja Nesek Adam, Tanja, Goranovic, Chrysanthos, Markoulias, Mina, Mathaios, Maria, Mylordou, Eleni, Achilleos, Pavlina, Kleanthous, Veronika, Kotanidi, Maria, Foka, Iwy, Charalabous, Anna, Alexandrou, Marios, Georgiou, Artemis, Patsalos, Sofia, Zepoy, Constantina, Constantinou, Petr, Piza, Tomas, Vymazal, Elisabeth, Wiborg, Louise, Bruhn, Karin, Kaasby, Karin Rehnholt Pedersen, Sanne, Mikkelsen, Marie, Collet, Anne, Langvad, Hanne, Andresen, Susanne, Fischer, Inger Ebbesen Kjærgård, Britta, Jepsen, Birthe, Husted, Morten, Bestle, Anne Marie Kodal, Tina Charlotte Bitsch Hansen, Anne Sofie Bomholt Pedersen, Tina Damgaar Thomsen, Anisette, Hoegenhaven, Mette, From, Tine Melgaard Frandsen, Grit, Henning, Anja, Hansen, Inger Abildgaard Bliksted, Luis Mario Tamayo, Pedro, Mogrovejo, Carolina, Palaez, Diego Rolando Morocho Tutillo, Cintia Valencia Hurtado, Maria Fernanda García, Diana, Alvarez, Fausto, Guerrero, Alexandra, Vasquez, Martin, Kütimets, Kadri, Tamme, Eneli, Anvelt, Lomangisi, Dlamini-Sserumaga, Carita, Löfqvist, Virpi, Lusenius, Outi, Kauppi, Jenni-Katarina, Sakki, Tarja, Tervo-Heikkinen, Ulla, Kesti, Merja, Merilainen, Elina, Karjula, Minna, Peltomaa, Auli, Palmu, Maarit, Ahtiala, Maija Anniina Valta, Hervé, Mentec, Gaëtan, Plantefève, Guillaume, Besch, Sébastien, Pili-Floury, Stanislas, Ledochowski, Marc Danguy des Déserts, Christophe, Giacardi, Cédric, Daubin, Audrey, Massard, Yann Le Guen, Agnès, Blanc, Simon, Mandaroux, Silvia Calvino Günther, Prune, Avogadro, Anthony, Radavidson, Jean, Turc, Sébastien, Jochmans, Hervé, Quintard, Laetitia, Boyer, Cédric, Bruel, François, Philippart, Philippe, Montravers, Enora, Atchade, Nadine, Flessel, Benoît, Chinardet, Léa, Soulisse, Cindy, Pillard, Delphine, Ngo, Benjamin, Bongiorno, Nathalie, Heitzler, Virginie, Souppart, Nathalie, Gautheret, Jean-Francois, Timsit, Fatiha, Essardy, Muriel, Fartoukh, Daisy, Mehay, Fabienne, Etourneau, Jean-Christophe, Farkas, Pascal, Beuret, Gabriel, Preda, Etienne De Montmollin, Vincent, Castelain, Ulrich, Jaschinski, Monika, Rothenfusser, Detlef, Kindgen-Milles, Thomas, Dimski, Christine, Fiedler, Tobias, Heinicke, Patrick, Meybohm, Tobias, Schulze, Marc, Bota, Sabrina, Pelz, Tobias, Odenthal, Martin, Christ, Kathrin, Bösl, Achilleas, Chovas, Sebastian, Stehr, Philipp, Simon, Sarah, Grotheer, Sebastian, Schüppel, Stefan, Schaller, Lea, Albrecht, Andeas, Stübner, Stephan, Graeser, Nina, Kolbe, Martina, Lausch, Anja, Diers, Ulf, Guenther, Reimer, Riessen, Martin, Roller, Irene Pearl Osei, Anita-Chrysolyte, Kusi-Appiah, Yakubu, H Yakubu, Belinda, Guadi-Gosh, Christos, Dragoumanis, Christos, Christofis, Nikolaos, Kazakos, Styliani, Bastani, Charalampos, Martinos, Vasileios, Bekos, Metaxia, Papanikolaou, Theonymfi, Papavasilopoulou, Anna, Efthymiou, Vasiliki, Chantziara, Anna, Kyriakoudi, Nikolaos, Kakaras, Chrisi, Diakaki, Aikaterini, Flevari, Charikleia, Nikolaou, Kounougeri, Katerina, Lamprini, Avramopoulou, Kyriaki, Tsikritsaki, Georgios, Gkiokas, Eirini, Pantiora, Chrysostomos, Katsenos, Eirini-Chysovalanto, Patsiou, Paraskevi, Alexandropoulou, Ioannis, Koutsodimitropoulos, Epaminontas, Farmakis, Konstantina, Nestora, Marinos, Chatzis, Eumorfia, Kondili, Stella, Soundoulounaki, Ourania, Mousafiri, Dimitra, Lepida, Antonia, Liarmakopoulou, Georgios, Papathanakos, Mrina, Oikonomou, Panagiotis, Ioannides, Dimitrios, Papadopoulos, Ioannis, Staikos, Maria, Stafylaraki, Bogdan, Raitsiou, Konstantinos, Mandis, Ifigenia, Ravani, Styliani, Kourelea, Aikaterini, Efthimiou, Giannoula, Thoma, Apostolos, Bakas, Konstantinos, Psarulis, Souzana, Anisoglou, Eirini, Papageorgiou, Evangelia, Michailidou, Thomai, Tholioti, Athena, Lavrentieva, Evdokia, Sourla, Anastasia, Spyropoulou, Nikolaos, Pantelas, Kristina Mariana Matei Stalika, Ioannis, Georgakas, Antigoni, Karathanou, Syragoula, Tsikriki, Aikaterini, Dimoula, Sofia, Kanakaki, Aristeidis, Vakalos, Konstantinos, Pagioulas, Judy Enamorado Enamorado, Gabor, Nardai, Fatime, Hawchar, Asbjorn, Blondal, Brynja, Rygvadottir, Rannveig, J Jonasdottir, Hrönn, Birgisdottir, Bhagyesh, Shah, Shuchi, Kaushik, Swagata, Tripathy, Mukta, Singh, Sonika, Agarwal, Manish, Gupta, Meraj, Ahmad, Kishore, Mangal, Vaibhav, Bhargava, Vilas, Kushare, Simant, Jha, Lakshay, Bhakhtiani, Manoj, Kamal, Arvind, Baronia, Ade, Susanti, Mayang Indah Lestari, Zulkifli, Zulkifli, Windu, Baskoro, Farid, Zand, Fatemeh, Zarei, Ata, Mahmoodpoor, Farshad, Heidari, Fateme, Jafaraghaee, Aidan, O'Shea, Fiona, O'Shea, Caroline, O'Donnell, Geraldine, Craig, Gerry, Fitzpatrick, Lisa, Dunne, Jennifer, Hastings, Brian, Marsh, Caitriona, Cody, Elizabeth, Campbell, Deirdre, Doyle, Michelle, Pacturanan, Christine, Sheehan, Annette, Carey, Charlotte, Carter, Regina, Mulvey, Damien O'Connell Rosemary Finn, Catherine, Motherway, Amy, Walsh, Jennifer, Kehoe, Shella, Delossantos, Jennifer, Lalor, Siobhan, O'Nuallain, Helena, Behan, Sandra, Mcpherson, Ailesh, Corcoran, Patricia, Gordon, Glenda, Rooney, Dassy, Levy, Mazal, Azencot, Vladimir, Gurevich, Alinoy, Lavy, Valentina, Bendelari, Romina, Marconi, Antonio, Barone, Chiara, Gatti, Andrea, Giampaoletti, Cinzia, Borgognoni, Davide Massimo Ghioldi, Arena, Raimondo, Giacomo, Castiglione, Anna Vita Bruno, Giorgia, Rubulotta, Antonella, Mo, Amalia, Corso, Salvatore, Girianni, Andrea, Bruni, Eugenio, Garofalo, Salvatore Maurizio Maggiore, Alessandro Di Risio, Italo, Calamai, Rosario, Spina, Savino, Spadaro, Carlo Alberto Volta, Antonella, Cotoia, Lucia, Mirabella, Laura, Maulicino, Giancarlo, Abregal, Maria, Donvito, Paolo, D'Ambrosio, Filipo, Binda, Ileana, Adamina, Alessandro, Galazzi, Alessandra, Negro, Rosanna, Vaschetto, Fabio, Capuzzi, Margherita, Boschetto, Lucia, Stivanello, Luciano, Bonaccorso, Chiara, Megna, Pasquale, Iozzo, Antonino, Rizzo, Giovanni, Scire, Maria Rosa Taibi, Francesca Paola Tranello, Antonio, Manzo, Lidia, Traina, Beatrice, Pastore, Attilio, Quaini, Gian Domenico Giusti, Gloria, Montaldi, Federica, Piergentili, Federica, Mancini, Simona, Casaioli, Francesco, Uccelli, Fabio, Guarracino, Adriana, Onelli, Valentina Di Gravio, Maria, Cossu, Oliva, Matrona, Monica, Rocco, Daniela, Alampi, Federica, Dellafiore, Flavia, Ranalli, Matteo, Bossolasco, Elisabetta, Brizio, Pina, Migliorino, Paolo, Cortellazi, Moris, Rosati, Francesco, D'Ambrosio, Catia, Quagliotto, Erik, Roman-Pognuz, Alberto, Peratoner, De Rosa, Silvia, Marina Alessandra Martin, Francesca De Sanctis, Paolo, Ciorba, Patrick, Toppin, Hyacinth, Harding-Goldson, Shunsuke, Taito, Nobuaki, Shime, Ryohey, Yamamoto, Fumiya, Kanda, Akemi, Hirao, Moritoki, Egi, Ayako, Noguchi, Satoru, Hashimoto, Umeda, Aya, Hideaki, Sakuramoto, Akira, Ohuchi, Jun, Kataoka, Kumi, Maruyama, Izumi, Nakayama, Yoshimasa, Nishime, Koji, Fujimoto, Kenji, Takahashi, Mayumi, Tsujimoto, Masako, Shimizu, Eunice, Tole, Malcolm, C Correia, Je Hyeong Kim, Sunghoon, Park, Kyung Chan Kim, Jonghyun, Baek, Jung-Min, Bae, So Young Park, Tai Sun Park, Heung Bum Lee, Seung Yong Park, Jisoo, Park, Lee, Yeon-Joo, Cho, Young-Jae, Sang-Miin, Lee, Kyeongman, Jeon, Seok Chan Kim, Jongmin, Lee, Hyun Keun Chee, Jin Won Huh, Yun Su Sim, Junghyun, Kim, Youjin, Chang, Jong-Joon, Ahn, Byung Ju Kang, Won-Yeon, Lee, Seok Jeong Lee, Nehat, Baftiu, Ivasr, Krastins, Sonia, Stiban, Michel El Feghaly, Elie, Gharios, Marie, Merheb, Mohamed, Benlamin, Ala, Khaled, Wesal Ali Belkhair, Majd, Tabib, Firas, Ashour, Ahmed, Elhadi, Osama Wanees Emhemid Tababa, Taha, Khaled, Soad Imhmed, R Alkhumsi, Abdualhamid, I Alshrif, Ahmed Ali Aboufray, Aya, Alabuzidi, Ahmed Ramadan Triki, Mala, Elgammudi, Hajer Ben Zahra, Enas, Soula, Maram Milud Said Al-Alawi, Hazem, Ahmed, Mohamed Abdurazzag Ali Ghula, Saulius, Vosylius, Lucie, Mouton, Touraj, Rastegar, Claude, Sertznig, Gilles, Martin, Christian, Theisen, Christian, Ferretti, Fränk, Gils, Marc, Gallion, Asmah, Zainudin, Laila Kamaliah Kamalul Bahrin, Shanti Rudra Deva, Azmin Huda Abdul Rahim, Sherliza, Wahab, W Nazaruddin, W Hassan, Wan Nasrudin Wan Ismail, Mohd Nazri Ali, Tien Meng Khoo, Noryani Mohd Samat, Jenny May Geok Tong, Nik Azman Nik Adib, Mohd Basri Mat Nor, Shanthi, Ratnam, Nahla, Ismail, Siti Rohayah Sulaiman, Kit Weng Foong, Anita, Alias, Ngu Pei Hua, Jorge Macias Zermeno, Daniel, Blanco, Karely, Duran, Claudia Lizbeth Lopez Nava, San Juan Roman Nandyelly, Luis Alejandro Sanchez-Hurtado, Brigitte, Tejeda-Huezo, Mario Del Moral Armengol, Luis Pedro Ambriz Nava, Jorge Guerra Herrera, Gilberto Felipe Vazquez de Anda, Humberto, Gallegos-Perez, Nancy, Hernandez-Sanchez, Lucia, Hernandez-Ponce, Luis, Gorordo-Delsol, Marcos, Hernandez-Romero, Saira, Gomez, Fernando, Molinar, Silvio, A Ñamendys-Silva, Juan, P Romero-Gonzalez, Daira, Gonzalez, Antonio, Landaverde, Miguel Ángel Sosa, Berenice, Navarro, José Ivan Rodriguez de Molina Serrano, Sergio Reyes Iburrigarro, Alejandro, Ibarra, Joaquin, Aguirre, Mayra, Martinez-Gonzalez, Nayeli Rocio Cañas Padilla, Ana Alícia Velarde Pineda, Missael Vladimir Espinoza Villafuerte, María Ocotlan Gonzalez Herrera, Battsetseg, Baasanjav, Abdelhamid, Hachimi, Mina, Elkhayari, Tarek, Dendane, Nisha Bhandari Subedi, Sabina Dhakal Pathak, Meena, Manandhar, Laura Van Gulik, Mark Van Den Brink, Peter Van Vliet, Benjamin, Gerretsen, Lettie Van Den Berg, Marina De Haan, Binny, Tuinstra, Paul, Kuijpers, Jennifer, Reijntjens, Jan Wytze Vermeijden, Martin, Rinket, Margijske, Vanroest, Auke, Reidinga, Bert, Loef, Willem, Dieperink, Marisa, Onrust, Tom, Dormans, Laura, Bormans, Matty, Koopmans, Rik, T Gerritsen, Arlette Van Den Elst, Mirjam, Evers, Oscar, Oiting, Rob, Wilting, Bart, Ramaker, Mark van der Kuil, Jan-Willem, Fijen, Lenneke, Haas, Jasper, Haringman, Lynette, Newby, Eileen, Gilder, Danielle, Hacking, Rica, Dagooc, Rima, Song, Hansjoerg, Waibel, Frances, Dawn, Jackie, Rapley, Llesley, Chadwick, Carmel, Chapman, Petra, Crone, Jonathan, Albrett, Peter, Marko, Jennifer, Goodson, Troy, Browne, Richard, Whitticase, Cheryl, Davidson, Harriet, Judd, Daniel, Owens, Tonia, Onyeka, Innocent, Ugwu, Rose, Ilesanmi, Prisca Olabisi Adejumo, Afolabi, Owojuyigbe, Anthony, Adenekan, Stella, Uba, Christiana, Chime, Deborah, Jibrin, Babangida John Sankey, Oyebola, Adekola, Simeon, Olanipekun, Mirjana, Shosolcheva, Vanja, Gievski, Andrijan, Kartalov, Filip, Naumovski, Biljana, Kuzmanovska, Angela, Trposak, Zaneta, Bogoevska-Miteva, Rodney, Rosalia, Brita Fosser Olsen, Britt, Sjobo, Karianne Dale Jensen, Drammen, Sykehus, Birgitte Fosser Johansen, Esben, Straede, Edda, Johansen, Inger Johanne Finnstrom, Annette, Toellefsen, Hege, Ostenjo, Hege, Bjorgen, Bjorn, Bratsberg, Elin, Kristoffersen, Elin Mari Skorstad, Siri, Hansen, Sylvi, Vullum, Gro Anne Lunde, Wenche, Arntsen, Mette, Lund, Gro Ringstad Akselsen, Kristina Reinertsen Monstad, Ane, Stenset, Hanne, Haugom, Bjoern, Monsen, Lisa, Høgvall, Siw, Trudvang, Britt, Galaaen, Siv Karin Malmin, Marit Hildegunn Andersen, Rita Foss Hargott, Yvonne, Andersen, Elin, Steffenak, Marit, Nyhus, Barbro, Meland, Madiha, Hashmi, Noelia, Rivas, Elizabeth, Maidana, Alberto de Jesús Ortiz, Dolly Mabel Bordon Cabral, Marcelo, Simi, Cesar, Aponte, Juan Carlos Rivas, Sirley, Gill, Amilcar, Garcia, Gloria, Alvarenga, Laura, Cespedes, Hugo, Perez, Maria Liz Moreira, Fidelina, Canete, Roberto, Gonzalez, Natalia, Monges, Mary, Coman, Marcelo, Pederzani, Natalia, Franco, Ferdinand, Aganon, Regina, Martinez, Debbie, Noblezada-Uy, Chris Gerome Ellazar, Franklin Dean Cerezo, Jose Emmanuel Palo, Cristal April Jane Aperocho, Michael, Isanan, Marta, Tubacka, Przemyslaw, Jasiewicz, Miroslaw, Czuczwar, Michal, Borys, Aleksandra, Gutysz-Wojnicka, Lidia, Glinka, Ryszard, Gawda, Jan, Bilawicz, Paula, Cabrita, João, Vieira, Margarida Ferreira Figueiredo, Cristiana Mota Pinheiro, Nelson, Antunes, Laura, Pedro, Fatima, Ferreira, Isabel, Parente, Maria, Varela, Fatima, Fernandes, Claudia, Martins, Abel, Viveiros, Raquel, Cavaco, Clara Santa Rita, Sofia, Dias, Ana Margarida Feranandes, Pedro, Silva, Catarina, Nunes, João, Cabral, Filpe, Pires, Hilaryano, Ferreira, Jacinta, Santos, Vitor Manuel Vaz Pinto, Bruno Miguel Bispo, Amelia, Ferreira, Elena, Molinos, Estevão, Lafuente, Ricardo, Gregorio, Humberto, Costa, Ângela, Lima, Susana, Ferreira, Vanda, Seromenho, Eulália, Luis, Idália, Valerio, Helena, Cesar, Ana, Tavares, Ahmed Subhy Alsheikhly, Saeed, Mahmood, Catalin Traian Guran, Alida, Moise, Daniela Carmen Filipescu, Mihail, Luchian, Mihai, Popescu, Monica Adriana Scutariu, Cristina, Petrisor, Natalia, Hagau, Ioana, Grigoras, Tatiana, Patrichi, Vitaly, Gusarev, Alexandra, Pivkina, Vladimir, Kulakov, Olga, Ignatenko, Julia, Kovaleva, Trina, Zhivotneva, Marina, Zhedaeva, Nikita, Matiushkov, Olga, Ershova, Natalya, Egorova, Victoria, Khoronenko, Danil, Baskakov, Dmitry, Sergeev, Michael, Piradov, Liudmila, Grishina, Marat, Magomedov, Evgeniy, Zuev, Uri, Gorokhovatsky, Anna, Leonova, Liudmila, Fadeeva, Vladislav, Belskiy, Dmitriy, Galishevskiy, Nadezhda, Zubareva, Maksim, Tribulev, Oksana, Zueva, Alexander, Kiselev, Nikolaj, Kamenshchikov, Ekaterina, Tokareva, Maxim, Petrushin, Irina, Starchenko, Isaac, Nshimyumuremyi, Jerome, Muhizi, Egide, Buregeya, Josue, Nzarora, Amer, Assiri, Maie Salem Ebaid, Ghaleb, Almekhlafi, Yasser, Mandourah, Jelena, Velickovic, Dejan, Veličković, Bojan, Jovanovic, Adi, Hadzibegovic, Branislava, Stefanovic, Vanja, Misic, Vesna, Bumbasirevic, Marija, Rajković, Milena, Stojanovic, Srđan, Gavrilovic, Maja, Stanojević, Aktham, Yaghi, Anton, Turčan, Peter, Firment, Garri, Slobodianiuk, Daria, Rabarova, Danca, Lančaričová, Janko, Vlaovic, Matjaž, Groznik, Milica, Lukic, Janja, Perme, Maja, Sostaric, Nejc, Umek, Tomislav, Mirkovic, Simon, Dolenc, Misa, Fister, Nika, Zorko, Andrej, Markota, Nomhle Princess Yeni, Phumele, Jali, Shelley, Schmollgruber, Muhommed Ridwaan Syed, Nivisha, Parag, Robert, Wise, Maria, Galiana, José Alejandro Navarro, Ana María De Pablo, Patricia, Albert, Pilar, Martinez, Yolanda, Mendiara, Barbara, Garcia, Ana Alabart Llinas, Marilyn, Riveiro, Elisabet, Gallart, Alba, Riera, Miquel, Sanz, Swagotika, Salo, Miguel Angel Gimenez Lajara, Montserrat Venturas Nieto, Rosa, Garcia, José Manuel Garcia Pena, Maria Carmen Gorgolas, Maria Aranzazu Isasi, Rafael, Sierra, Federico, Gordo, Isabel, Conejo, Vicent, Salvà-Costa, Carolina, Garzón-Tovar, Sara, Lospitao, Rafael, Gonzalez, Pedro, Gutierrez, Mercè, Girona, Jordi, Adamuz, Pablo Garcia Olivares, José Peral Gutierrez de Ceballos, Celia, Tirado, Irene De Wit, Ana Belén Curto Polo, Maria Del Mar Diaz Salcedo, Javier, Ripolles-Melchor, Eugenio, Martinez-Hurtado, Jorge Duerto Alvarez, María Luisa Bravo Arcas, Juan Ignacio Torres Gonzalez, Ana Belén Sánchez de la Ventana, Pablo Lopez-Arcas Calleja, Raquel Garcia Alvarez, Purificacion Sanchez Zamora, Alvaro Ortega Guerrero, Rosario, Cosano, Jonathan, Perez-Vacas, Margarita, Campos-Perez, Emma Moreno Barreiro, Losune Cano Sanchez, Monica Garcia Diaz, Raquel, Jimenez, Lorena Del Rio Cabajo, Daniel Sancho Muriel, Helena Fernandez Alonso, Ana Wensell Fernández, Isabel Santín Piñan, Guillermo Muñiz Albaiceta, Maria Cristina Iglesias Fernandez, Francisco Javier Saenz Abos, Pablo, Monedero, Ramon Molina Chueca, Lydia Gallego Aguirre, Silvia Call Manosa, Carmen Partera Luque, Neus, Calpe, Monica Recio Losilla, Meritxell Tapia Fores, Olga, Farre, Oscar, Fernandez, M Del Rosario Villar Redondo, Donaldo, S Arteta Arteta, Maria Angeles Hurtado Sanchez, Cristina Paños Espinosa, Laura Martinez Reyes, Laura Claramunt Domenech, Carmen Velasco Guillén, Josep Trenado Alvarez, Mercedes Del Cotillo, Jesus Emilio Barrueco-Francioni, Belen Burgos Conde, Maria Pilar Sogues Blanco, Maria Luisa Blasco, Ana Isabel Clement, Clara, Hurtado, Luz Coronado Sanz, David, Perez-Torres, Estefanía, Prol-Silva, Jorge, Pereira, Iván Areán González, Anastasio Espejo Cano, Cesar Rodriguez Nuñez, Inmaculada Lorenzo Fernadez, Alejandra Azahara Marguello Fernandez, Rosa Del Bosque Diez, Badiola, Hilario, Begoña, Zalba-Etayo, Ana, Pascual-Bielsa, Preveen, Banwarie, Dick, Nahar, Alisha van Axel, Naraindath, N Boedjawan, Erika Backlund Jansson, Ann-Sofie, Malvemyr, Lotta, Johansson, Ulla, Sandberg, Catarina, Tingsvik, Gunilla, Mattsson, Gun, Löf, Martin, Spångfors, Mona, Ringdal, Sebastian, Geijer, Lotti, Orvelius, Mia, Hylen, Caroline, Lagerhäll, Eva, Åkerman, Viveca Hamback Hellkvist, Ulrica, Mickelsson, Ewa, Wahlbom, Ing-Marie, Larsson, Ewa, Wallin, Filippo, Boroli, Solenne, Ory, Margaret Lynn Jong, Alexander, Dullenkopf, Martin, Lang, Yvan, Fleury, Marianne, Maus, Nawfel, Ben-Hamouda, Anne, Fishman, Mei Yu Hsu, Shu Chuan Chang, Konlawij, Trongtratul, Chaiwut, Sawawiboon, Sunthiti, Morakul, Bodin, Khwannimit, Keevan, Singh, Dale, Ventour, Dianne, Figaro-Barclay, Sasha, Sankar-Maharaj, Mhamed Sami Mebazaa, Salma, Kamoun, Souheil, Elatrous, Lamia, Besbes, Fekri, Abroug, Walid, Naija, Youssef Zied Elhechmi, Walid, Sellami, Zied, Hajjej, Takoua, Merhabene, Imen, Talik, Ozlem Ozkan Kuscu, Ozcengiz, Dilek, Avşar, Zerman, Hayriye Cankar Dal, Sema, Turan, Semih, Aydemir, Hakan, Yilmaz, Duygu Kayar Calili, Seval, İzdes, Melike, Cengiz, Ayça, Gümüş, Banu, Taşdemir, Ali, Kağnıcı, Mustafa, Ay, Serap Avcı Ay, Gulbahar, Caliskan, Turkay, Akbas, Abidin Oner Balbay, Serdar, Efe, Volkan, Inal, Gülseren, Elay, Pınar, Karabacak, Boğaç, Özserezli, Evren, Şentürk, Oktay, Demirkiran, Suha, Bozbay, Elif, Erdogan, Mustafa, Akker, Nebia, Peker, Asu, Ozgultekin, Sibel Ocak Serin, Can, Turan, Gulsah, Karaoren, Senay, Goksu, Sait, Karakurt, Huseyin, Arikan, Fethi, Gül, İsmail, Cinel, Iskender, Kara, Hasan Nabi Undar, Yesim Serife Bayraktar, Jale Bengi Çelik, Murat Emre Tokur, Demet Tok Aydin, İsmail, Yildiz, Beysim, Özcan, Başar, Erdivanli, Ahmet, Eroglu, Devrim, Akdağ, Nurdan, Ünlü, Adonis, Dungca, Ashwaq, Ali, Bindu, Thankamma, Paul Eric Reyes, Sini, John, Ajitha, Rajendran, Fatima Kasem El Ahmad, Kathleen Ann Smiley, Susanna, Hojden, Mia Thorning Miller, Vishnu Das Sasidharan Nair, Maria Gracia San Antonio, Khaled Al Qawasmeh, Sabah Abu Shawish, Hilary, Twiggs, Ines, Rosado, Volodymyr, Babych, Faye, Morren, Charlotte, Young, Nicola, Vaughan-Jones, Stephanie, Harris, Karen, Burns, Carmel, Georgiev, Rosina, Shayamano, Ian, Kerslake, Peter, Creber, Ana, Vochin, Catherine, O'Brien, Paul, Caddell, Samantha, Hagan, Mandy, Hughes, Tomasz, Torlinski, James, Sherwin, Santhana, Kannan, Amber, Markham, Richard, Lebon, Jason, Cupitt, Julius, Cranshaw, Nigel, White, Victoria, Marriott, Wendy, Milner, Casiano Barrera Groba, Joao, Azoia, Petra, Polgarova, Shaly, George, Ritoo, Kapoor, Ceri, Lynch, Nathalie, Fox, Karen, Cranmer, Natalie, Fox, Thomas, Llewellym, Kelly, Matthews, Louise, Maltby, Jowena, Ibao, Karen, Boulton, Rachel, Jarman, Karen, Baxter, Ashok Sundai Raj, Arif, Moghal, Joanne, White, Suzanne, Barrowcliffe, Mark, Pulletz, Vaarisan, Ganeshalingam, Rosaleen, Baruah, Carole, Boulanger, Helen, Baker, Justin, Woods, Poe Poe Ei, Vongayi, Ogbeide, Paul, Hayden, Jennifer, Hughes, Madhu, Balasubramanian, Armorel, Salberg, Rajnish, Saha, Dagmar, Holmquist, Claire, Derbyshire, Neil, Smith, Elizabeth, Stones, Jane, Ademokun, Monica, Popescu, Maria Schofield Legorburo, Samantha, North, Carole, Brett, Helen, Jaundoo, Jayne, Craig, Simon, Whiteley, Clare, Howcroft, Liz, Wilby, Peter, Delve, David, Shaw, Karen, Williams, Ingeborg, D Welters, Jane, Mcmullen, Stephen, Brett, Leah, Flores, Treiza, Trueman-Dawkins, Mae, Templeton, John, Adams, Catherine, Smith, John, Prowle, Heather, Byers, Andrea, Mcdonnell, Bernd Oliver Rose, Rosie, Reece-Anthony, Luis, Mendes, Marcela, Vizcaychipi, Rhian, Bull, Grace, Lacaden, Eleanor, Santiago, Carlos Castro Delgado, Sarah, Farnell-Ward, Elaine, Thorpe, Justine, Somerville, Anne, Williams, Donna, Cummings, Helen, Derrick, Sarah, Brumwell, Claire, Randell, Nicola, Mccann, Emma, Aves, Gillian, Berry, Tamas, Szakmany, Una, Gunter, Paul, Pulak, Nikki, Sarkar, Kerry, Wright, Vitor, Gomes, Jones, Jo, Ruth, Palfrey, Julie, Camsooksai, Abby, Lewis, Antony, Eneas, Ascanio, Tridente, Louise, Barr, Beverley, Thomas, Emma, Parkin, Daniel, Horner, Christian, Frey, Suzanne, Bench, Rachel, Baumber, Phil, Broadhurst, Matthew, Jackson, Lynne, Williams, Michele, Clark, Jonathan, Paddle, Sarah, Bean, Sarah, Buckley, Christopher, Palfreeman, Sophie, Liu, Nicola, Allison, Ben, Attwood, Penny, Parsons, Victoria, Houghton, Sarah Jane Turner, David, Higgins, Egidija, Bielskute, Nicola, Horrigan, Reni, Jacob, Karen, Habgood, Ahmed, Zaki, Amy, Collins, Jenny, Lord, Charalice, Ramiro, Agnieszka, Kubisz-Pudelko, Michelle, Kotze, Helen, Williams, Ihor, Iovenko, Alexander, Tsarev, Arturo, Briva, Gabriela, Mendez, Lena, Napolitano, Magnus, Teig, Jarone, Lee, Gabriel Enrique Rodriguez, Talia, Ben-Jacob, Christopher, Potestio, Timothy, Eng, Dea, Mahanes, Ashish, Khanna, Abhijit, Duggal, Masakatsu, Nananmori, Manuel, Lois, Anna, Diaz, Kunal, Karamchandani, Cheryl, Bealer, Cindy, Barefield, Dorothy, Terry, Pauline, Fivecoat, Olakunle, Idowu, Juan, Cata, Tara, Clesi, Jessica, Peterson, Kevin, Hatton, Jasdeep, Dhaliwal, Dorothee, Mueller, Jing, Tao, Ashley Szabo Eltorai, Stephen, M Pastores, Natalie, Remor, Janel, Salazar, Diane, Barkas, Aaron, Joffe, Christopher, Barnes, Carrie, Sona, Marilyn, Schallom, Jack, Short, Javier, Lorenzo, Ingrid Von Der Osten, Marta, Borkowska, Mireia, Llaurado-Serra, Liesbet, Demarré, Vincianne, Pleitinckx, Cynthia, Xing, Anne-Sophie, Debue, Stefan, Goller, Elsa, Afonso, Gusarov, V, Eugeniya, Larina, Llaurado-Serra, M, Yalim, Dikmen, DecubICUs Study Team, European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, Muzha, D., Ribas, A.M., Lipovesty, F., Loudet, C., Coyer, F., Eller, P., Mostafa, N., Honoré, P.M., Telleria, V.M., Smajic, J., Nogueira, P.C., Nafees, KMK, Hentchoya, R., Rose, L., Soledad, J., Lin, F., Cardenas, Y., Reyes, A.G., Sustic, A., Mpouzika, M., Vymazal, T., Jensen, H.I., Aguirre-Bermeo, H., Maddison, L., Valta, M., Calvino-Gunther, S., Bloos, F., Adipa, F.E., Koulouras, V., Enamorado, J., Ágoston, Z., Birgisdóttir, H., Gupta, A., Gurjar, M., Kilapong, B., Hashemian, S.M., Martin-Loeches, I., Benbenishty, J., Cortegiani, A., Fletcher, K., Hayashi, Y., Waweru-Siika, W., Abidi, K., Lee, S.M., Hadri, B., Dolgusevs, M., Abillama, F.F., Jovaisa, T., Thix, C., Elhadi, M., Nor, B.M., Ratnam, S., Mazlan, M.Z., Maiyalagan, S., Sánchez-Hurtado, L., Belii, A., Naranpurev, M., Gautam, P., De Lange, D., Parke, R., Ilesanmi, R.E., Shosholcheva, M., Petosic, A., Lind, R., Ffarcsi, M.H., Bogarin, J., Hernandez, A.M., Mikaszewska-Sokolewicz, M., Sousa, B., Tomescu, D., Sandesc, D., Twagirumugabe, T., Gusarov, V., Ebaid, M., Jankovic, R., Slobodianiuk, G., Martonova, A., Knafelj, R., Mer, M., Maseda, E., Panka, B., Schefold, J.C., Joelsson-Alm, E., Trongtrakul, K., Merritt-Charles, L., Besbes, L.O., Dikmen, Y., Zgrzheblovska, L., Fielding, M., Rubulotta, F., Khanna, A.K., Saager, L., von der Osten, I., Greca, A., Cani, A., Xhindi, N., Hyska, G., Pinto, S., Alves, P., Esposito, R., Valgolio, E., Minope, JTS, Abdala, A., Ayala, M., Bravo, S., Bantar, A., Delgado, P., Badariotti, G., Lipovestky, F., Diaz, A., Saul, P., Setten, M., Aucapina, A., Acosta, Y., Gonzalez, V., Camputaro, L., Baccaro, F., Villa, R., Mastantuono, M., Dean, E., Rostello, O.F., Brizuela, P., Bartoli, J.R., Guereschi, M., Quiroga, C., Putruele, S., Villegas, P., Curilen, V., Fernandez, R., Nocheretti, M.G., Escalante, R.G., Loudet, C.I., Fernandez, S., Gonzalez, A.L., Alvarez, G.A., Iglesias, F., Chaparro, S., Zakalik, G., Pagella, G., Baini, M., Campos, P.A., Sabbag, I., Schmukler, A., Fonseca, I.P., Alvarez, G.M., Ramirez, M., Tapia, F., Bascary, C.A., Del Valle Gimenez, G., Bertoletti, F.P., Milioto, E., Bonsignore, PJM, Fernandez, M.A., Smith, J., Chimunda, T., Thompson, L., Maguire, T., Chaboyer, W., Watts, S., Mitchell, M., Powell, M., Lye, I., Parsons, L., Baker, N., Reynolds, C., Thompson, A., Masters, K., Sosnowski, K., Morrison, L., Leslie, G.D., Lakshmanan, R., Tabah, A., Brown, W., McDowell-Skaines, S., McLucas, A., Smith, C., Tallot, M., Jones, S., Barakat-Johnson, M., Leong, T., Butcher, R., Martin, K., Douschan, P., von Lewinski, D., Schmutz, R., Kolussi, U., Salman, F., Ateya, Z., De Decker, K., Van Regenmortel, N., Jans, A., Wijnands, P., Coremans, S., Honore, P.M., De Bels, D., Depuydt, T., Paillet, C., Jacquet, L.M., Swinnen, W., Hannes, F., Mergeay, M., Van de Velde, S., Allaert, S., Hoste, P., Borin, C., Balon, S., Fraipont, V., Biston, P., De Schryver, N., Dugernier, T., Van Cotthem, I., de Almeida, A.O., Jorge, S.A., Becker, D., Schmidt, R.C., Oliveira, E., Ramalho, A., Mazocoli, E., Fioretti, A., Barros, E., Serpa, L., Bianchini, S., Campanili, T., Pantaleao, T., Garcia, P.C., Ronchini, ALV, Santos, R., Manap, NBA, Bagshaw, S., Carney, D., Davidow, J., Rokosh, E., Laizner, A.M., Smith, S., McQuirter, M., Kampayana, B.S., Favre, R., Sills, M., Dallaire, J., Becker, C., Microys, S., Bowes, B., Lajeunesse, J., Ghosh, R., Baptiste-Savoie, J., Raizman, R., Suen, G., Taghavi, N., Smith, O., Fielding, C., Canales, J., Molina, P., Chaparro, J., Sepulveda, M.I., Zamorano, MJF, Rocha, P., Villanueva, X., Araya, P., Dayan, M., Avalos, F., Li, X., Liu, Y., Chen, X., Jiang, Z., Yang, J., Chen, J., Yang, L., Wang, K., Gao, J., Fang, X., Zhao, R., Xia, X., Liu, H., Li, J., Wang, H., Meng, G., Di, Y., Wang, D., Zhao, R.H., Hu, L.P., Peipei, X., Jiao, Q.F., Wang, H.Y., Xia, C.J., Ye, M., Wan, Y., Wang, W., Ding, Y., Ren, A., Gao, Y., Li, Q., Du, G., Shen, Y., Li, N., Yuan, C., Tan, L., Lin, Q., Guo, H., Yan, H., Xu, X., Zhang, W., Liang, J., Zhang, L., Tian, E., Zhao, Q., InSu, L., Dong, J., Gu, Y., Zhao, L., Qiao, H., Tuo, L., Lv, M., Zhu, J.Y., Zhu, J., Wei, Y., Liu, M., He, Y., Cheng, J., Liu, J., Jia, N., Wei, D., Wu, X., Duan, H., Lin, D., Liang, Q., Luo, X., Xiong, Y., Huang, R.F., Fu, J., Zan, T., Shi, Z., Long, Y., Lei, Y., Liu, X., Yumei, C., Wang, L., Zhang, Y., Xu, Y., Cheng, X., Zhijuan, W., Sun, C., Song, J., Wang, Y., Yuan, Y., Huang, Q., Yang, F., Wu, Y., Bai, X., Zheng, H., Song, M., Sun, Y., Li, Z., Luo, F., Li, L.C., Zhang, G., Xiao, L., Yu, T., Gao, G., Wei, W., Wang, F., Han, T., Li, T., Zeng, Q., Zeng, J.M., Pan, F., Wang, J., He, G., Chen, H., Zhang, F., Chao, Y., Chunhua, G., Yao, X., Bai, D., Liu, L., Liang, X., Zhang, N., Zhang, A., Hu, X., Zhang, H., Wang, R., Tak, P.S., Ho, S.W., Jiang, Q.X., Ding, X., Hong, L., Miao, L., Feng, Z., Huang, L., Wu, J., Guo, J., Zhang, B., Ma, C., Han, Y., Liu, C., Ding, M., Luan, L., Zheng, J., Lv, S., Jiang, S., Cao, W., Xue, X., Liu, G., Wei, X., Jiang, Y., Yao, Z., Gao, L., Zhao, W., Jiang, M., Hao, J., Zhang, J., Song, C., Chen, F., Wang, S., Hu, L., Cao, D., Wan, J., Wang, X., Shao, H., Zhang, Z., Cui, X., Fan, L., Yu, M., Li, B., Li, C., Chen, W., Li, Y., Zhigang, Z., Yuchen, W., Mu, C., Zhu, G., Bo, Q., Li, L., Chen, M., Jiang, J.H., Yin, H., Pang, X., Gong, Y.Y., Yang, S., Yan, X., Zheng, X., Lei, D., Lei, L., Guo, Y., Yu, J., Sun, W., Bi, A., Li, W., Ni, D., Wu, Z., Song, B., Fei, Q., Xiaoyan, Y., Ran, Q., Xixi, L., Jiao, X., Ji, H., Zhiping, S., Hong, M., Jianhong, M., Hao, Y., Yin, L., Hui, C., Ju, W., Huo, Y., Chen, L., Yan, Y., Bao, G., Cao, Y., Xu, L., Guixiang, J., Zhao, H.M., Huang, X., Dai, Z., Jian, Y., Tian, Z., Cao, Z.Q., Li, M., Ouyang, F., Ma, F., Jin, W., Ge, L., Wu, S., Yuan, W., Chen, T., Shi, G., Chen, Z., Liu, K., Lin, X., Yuemen, L., Lijuan, S., Tian, X.F., Dong, Y., Bocui, N., Wang, G., Zhao, Y., Yang, Q., Hu, R.L., Li, X.Q., Yu, Z.J., Yao, Y., Deng, X., Xiao, Y., Xie, Y., Yang, Y., Yang, H., Zhou, Y., Xiao, M., Tian, Y., Gama, LMS, Hernandez, J.S., Caicedo, N., Marin, J., Ochoa, M.E., Gomez, M., Rojas-Suarez, J., Gonzalez, J., Reyes, AJG, Chapeta, E., Orozco, E., Filipović-Grčić, I., Vuković, A., Pečenković, S., Šuput, A., Zivanovic-Posilovic, G., Bozena, A., Udiljak, N., Milic, M., Radivojevic, R.C., Mihaljevic, S., Matas, M., Tonkovic, D., Čuljak, H., Herceg, I., Pavlisa, G., Dobric, M., Beker, T., Adam, V.N., Goranovic, T., Markoulias, C., Mathaios, M., Mylordou, M., Achilleos, E., Kleanthous, P., Kotanidi, V., Foka, M., Charalabous, I., Alexandrou, A., Georgiou, M., Patsalos, A., Zepoy, S., Constantinou, C., Piza, P., Wiborg, E., Bruhn, L., Kaasby, K., Pedersen, K.R., Mikkelsen, S., Collet, M., Langvad, A., Andresen, H., Fischer, S., Kjærgård, I.E., Jepsen, B., Husted, B., Bestle, M., Kodal, A.M., Hansen, TCB, Pedersen, ASB, Thomsen, T.D., Hoegenhaven, A., From, M., Frandsen, T.M., Henning, G., Hansen, A., Bliksted, I.A., Tamayo, L.M., Mogrovejo, P., Palaez, C., Tutillo, DRM, Hurtado, C.V., García, M.F., Alvarez, D., Guerrero, F., Vasquez, A., Kütimets, M., Tamme, K., Anvelt, E., Dlamini-Sserumaga, L., Löfqvist, C., Lusenius, V., Kauppi, O., Sakki, J.K., Tervo-Heikkinen, T., Kesti, U., Merilainen, M., Karjula, E., Peltomaa, M., Palmu, A., Ahtiala, M., Valta, M.A., Mentec, H., Plantefève, G., Besch, G., Pili-Floury, S., Ledochowski, S., Déserts, MDD, Giacardi, C., Daubin, C., Massard, A., Le Guen, Y., Blanc, A., Mandaroux, S., Günther, S.C., Avogadro, P., Radavidson, A., Turc, J., Jochmans, S., Quintard, H., Boyer, L., Bruel, C., Philippart, F., Montravers, P., Atchade, E., Flessel, N., Chinardet, B., Soulisse, L., Pillard, C., Ngo, D., Bongiorno, B., Heitzler, N., Souppart, V., Gautheret, N., Timsit, J.F., Essardy, F., Fartoukh, M., Mehay, D., Etourneau, F., Farkas, J.C., Beuret, P., Preda, G., De Montmollin, E., Castelain, V., Jaschinski, U., Rothenfusser, M., Kindgen-Milles, D., Dimski, T., Fiedler, C., Heinicke, T., Meybohm, P., Schulze, T., Bota, M., Pelz, S., Odenthal, T., Christ, M., Bösl, K., Chovas, A., Stehr, S., Simon, P., Grotheer, S., Schüppel, S., Schaller, S., Albrecht, L., Stübner, A., Graeser, S., Kolbe, N., Lausch, M., Diers, A., Guenther, U., Riessen, R., Roller, M., Osei, I.P., Kusi-Appiah, A.C., Yakubu, Y.H., Guadi-Gosh, B., Dragoumanis, C., Christofis, C., Kazakos, N., Bastani, S., Martinos, C., Bekos, V., Papanikolaou, M., Papavasilopoulou, T., Efthymiou, A., Chantziara, V., Kyriakoudi, A., Kakaras, N., Diakaki, C., Flevari, A., Nikolaou, C., Katerina, K., Avramopoulou, L., Tsikritsaki, K., Gkiokas, G., Pantiora, E., Katsenos, C., Patsiou, E.C., Alexandropoulou, P., Koutsodimitropoulos, I., Farmakis, E., Nestora, K., Chatzis, M., Kondili, E., Soundoulounaki, S., Mousafiri, O., Lepida, D., Liarmakopoulou, A., Papathanakos, G., Oikonomou, M., Ioannides, P., Papadopoulos, D., Staikos, I., Stafylaraki, M., Raitsiou, B., Mandis, K., Ravani, I., Kourelea, S., Efthimiou, A., Thoma, G., Bakas, A., Psarulis, K., Anisoglou, S., Papageorgiou, E., Michailidou, E., Tholioti, T., Lavrentieva, A., Sourla, E., Spyropoulou, A., Pantelas, N., Stalika, KMM, Georgakas, I., Karathanou, A., Tsikriki, S., Dimoula, A., Kanakaki, S., Vakalos, A., Pagioulas, K., Enamorado, J.E., Nardai, G., Hawchar, F., Blondal, A., Rygvadottir, B., Jonasdottir, R.J., Birgisdottir, H., Shah, B., Kaushik, S., Tripathy, S., Singh, M., Agarwal, S., Gupta, M., Ahmad, M., Mangal, K., Bhargava, V., Kushare, V., Jha, S., Bhakhtiani, L., Kamal, M., Baronia, A., Susanti, A., Lestari, M.I., Zulkifli, Z., Baskoro, W., Zand, F., Zarei, F., Mahmoodpoor, A., Heidari, F., Jafaraghaee, F., O'Shea, A., O'Shea, F., O'Donnell, C., Craig, G., Fitzpatrick, G., Dunne, L., Hastings, J., Marsh, B., Cody, C., Campbell, E., Doyle, D., Pacturanan, M., Sheehan, C., Carey, A., Carter, C., Mulvey, R., Finn, DOR, Motherway, C., Walsh, A., Kehoe, J., Delossantos, S., Lalor, J., O'Nuallain, S., Behan, H., McPherson, S., Corcoran, A., Gordon, P., Rooney, G., Levy, D., Azencot, M., Gurevich, V., Lavy, A., Bendelari, V., Marconi, R., Barone, A., Gatti, C., Giampaoletti, A., Borgognoni, C., Ghioldi, D.M., Raimondo, A., Castiglione, G., Bruno, A.V., Rubulotta, G., Mo, A., Corso, A., Girianni, S., Bruni, A., Garofalo, E., Maggiore, S.M., Di Risio, A., Calamai, I., Spina, R., Spadaro, S., Volta, C.A., Cotoia, A., Mirabella, L., Maulicino, L., Abregal, G., Donvito, M., D'Ambrosio, P., Binda, F., Adamina, I., Galazzi, A., Negro, A., Vaschetto, R., Capuzzi, F., Boschetto, M., Stivanello, L., Bonaccorso, L., Megna, C., Iozzo, P., Rizzo, A., Scire, G., Taibi, M.R., Tranello, F.P., Manzo, A., Traina, L., Pastore, B., Quaini, A., Giusti, G.D., Montaldi, G., Piergentili, F., Mancini, F., Casaioli, S., Uccelli, F., Guarracino, F., Onelli, A., Di Gravio, V., Cossu, M., Matrona, O., Rocco, M., Alampi, D., Dellafiore, F., Ranalli, F., Bossolasco, M., Brizio, E., Migliorino, P., Cortellazi, P., Rosati, M., D'Ambrosio, F., Quagliotto, C., Roman-Pognuz, E., Peratoner, A., De Rosa, S., Martin, M.A., De Sanctis, F., Ciorba, P., Toppin, P., Harding-Goldson, H., Taito, S., Shime, N., Yamamoto, R., Kanda, F., Hirao, A., Egi, M., Noguchi, A., Hashimoto, S., Aya, U., Sakuramoto, H., Ohuchi, A., Kataoka, J., Maruyama, K., Nakayama, I., Nishime, Y., Fujimoto, K., Takahashi, K., Tsujimoto, M., Shimizu, M., Tole, E., Correia, M.C., Kim, J.H., Park, S., Kim, K.C., Baek, J., Bae, J.M., Park, S.Y., Park, T.S., Lee, H.B., Park, J., Yeon-Joo, L., Young-Jae, C., Jeon, K., Kim, S.C., Lee, J., Chee, H.K., Huh, J.W., Sim, Y.S., Kim, J., Chang, Y., Ahn, J.J., Kang, B.J., Lee, W.Y., Lee, S.J., Baftiu, N., Krastins, I., Stiban, S., Feghaly, M.E., Gharios, E., Merheb, M., Benlamin, M., Khaled, A., Belkhair, W.A., Tabib, M., Ashour, F., Elhadi, A., Tababa, OWE, Khaled, T., Alkhumsi, SIR, Alshrif, A.I., Aboufray, A.A., Alabuzidi, A., Triki, A.R., Elgammudi, M., Zahra, H.B., Soula, E., Al-Alawi, MMS, Ahmed, H., Ghula, MAA, Vosylius, S., Mouton, L., Rastegar, T., Sertznig, C., Martin, G., Theisen, C., Ferretti, C., Gils, F., Gallion, M., Zainudin, A., Bahrin, LKK, Deva, S.R., Rahim, AHA, Wahab, S., Hassan, WNW, Ismail, WNW, Ali, M.N., Khoo, T.M., Samat, N.M., Tong, JMG, Adib, NAN, Nor, MBM, Ismail, N., Sulaiman, S.R., Foong, K.W., Alias, A., Hua, N.P., Zermeno, J.M., Blanco, D., Duran, K., Nava, CLL, Nandyelly, SJR, Sanchez-Hurtado, L.A., Tejeda-Huezo, B., Del Moral Armengol, M., Nava, LPA, Herrera, J.G., de Anda, GFV, Gallegos-Perez, H., Hernandez-Sanchez, N., Hernandez-Ponce, L., Gorordo-Delsol, L., Hernandez-Romero, M., Gomez, S., Molinar, F., Ñamendys-Silva, S.A., Romero-Gonzalez, J.P., Gonzalez, D., Landaverde, A., Sosa, M.Á., Navarro, B., de Molina Serrano, JIR, Iburrigarro, S.R., Ibarra, A., Aguirre, J., Martinez-Gonzalez, M., Padilla, NRC, Pineda, AAV, Villafuerte, MVE, Herrera, MOG, Baasanjav, B., Hachimi, A., Elkhayari, M., Dendane, T., Subedi, N.B., Pathak, S.D., Manandhar, M., Van Gulik, L., Van Den Brink, M., Van Vliet, P., Gerretsen, B., Van Den Berg, L., De Haan, M., Tuinstra, B., Kuijpers, P., Reijntjens, J., Vermeijden, J.W., Rinket, M., Vanroest, M., Reidinga, A., Loef, B., Dieperink, W., Onrust, M., Dormans, T., Bormans, L., Koopmans, M., Gerritsen, R.T., Van Den Elst, A., Evers, M., Oiting, O., Wilting, R., Ramaker, B., van der Kuil, M., Fijen, J.W., Haas, L., Haringman, J., Newby, L., Gilder, E., Hacking, D., Dagooc, R., Song, R., Waibel, H., Dawn, F., Rapley, J., Chadwick, L., Chapman, C., Crone, P., Albrett, J., Marko, P., Goodson, J., Browne, T., Whitticase, R., Davidson, C., Judd, H., Owens, D., Onyeka, T., Ugwu, I., Ilesanmi, R., Adejumo, P.O., Owojuyigbe, A., Adenekan, A., Uba, S., Chime, C., Jibrin, D., Sankey, B.J., Adekola, O., Olanipekun, S., Shosolcheva, M., Gievski, V., Kartalov, A., Naumovski, F., Kuzmanovska, B., Trposak, A., Bogoevska-Miteva, Z., Rosalia, R., Olsen, B.F., Sjobo, B., Jensen, K.D., Sykehus, D., Johansen, B.F., Straede, E., Johansen, E., Finnstrom, I.J., Toellefsen, A., Ostenjo, H., Bjorgen, H., Bratsberg, B., Kristoffersen, E., Skorstad, E.M., Hansen, S., Vullum, S., Lunde, G.A., Arntsen, W., Lund, M., Akselsen, G.R., Monstad, K.R., Stenset, A., Haugom, H., Monsen, B., Høgvall, L., Trudvang, S., Galaaen, B., Malmin, S.K., Andersen, M.H., Hargott, R.F., Andersen, Y., Steffenak, E., Nyhus, M., Meland, B., Hashmi, M., Rivas, N., Maidana, E., de Jesús Ortiz, A., Cabral, DMB, Simi, M., Aponte, C., Rivas, J.C., Gill, S., Garcia, A., Alvarenga, G., Cespedes, L., Perez, H., Moreira, M.L., Canete, F., Gonzalez, R., Monges, N., Coman, M., Pederzani, M., Franco, N., Aganon, F., Martinez, R., Noblezada-Uy, D., Ellazar, C.G., Cerezo, F.D., Palo, J.E., Aperocho, CAJ, Isanan, M., Tubacka, M., Jasiewicz, P., Czuczwar, M., Borys, M., Gutysz-Wojnicka, A., Glinka, L., Gawda, R., Bilawicz, J., Cabrita, P., Vieira, J., Figueiredo, M.F., Pinheiro, C.M., Antunes, N., Pedro, L., Ferreira, F., Parente, I., Varela, M., Fernandes, 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Lee S.J., Baftiu N., Krastins I., Stiban S., Feghaly M.E., Gharios E., Merheb M., Benlamin M., Khaled A., Belkhair W.A., Tabib M., Ashour F., Elhadi A., Tababa O.W.E., Khaled T., Alkhumsi S.I.R., Alshrif A.I., Aboufray A.A., Alabuzidi A., Triki A.R., Elgammudi M., Zahra H.B., Soula E., Al-Alawi M.M.S., Ahmed H., Ghula M.A.A., Vosylius S., Mouton L., Rastegar T., Sertznig C., Martin G., Theisen C., Ferretti C., Gils F., Gallion M., Zainudin A., Bahrin L.K.K., Deva S.R., Rahim A.H.A., Wahab S., Hassan W.N.W., Ismail W.N.W., Ali M.N., Khoo T.M., Samat N.M., Tong J.M.G., Adib N.A.N., Nor M.B.M., Ismail N., Sulaiman S.R., Foong K.W., Alias A., Hua N.P., Zermeno J.M., Blanco D., Duran K., Nava C.L.L., Nandyelly S.J.R., Sanchez-Hurtado L.A., Tejeda-Huezo B., Del Moral Armengol M., Nava L.P.A., Herrera J.G., de Anda G.F.V., Gallegos-Perez H., Hernandez-Sanchez N., Hernandez-Ponce L., Gorordo-Delsol L., Hernandez-Romero M., Gomez S., Molinar F., Namendys-Silva S.A., Romero-Gonzalez J.P., Gonzalez D., Landaverde A., Sosa M.A., Navarro B., de Molina Serrano J.I.R., Iburrigarro S.R., Ibarra A., Aguirre J., Martinez-Gonzalez M., Padilla N.R.C., Pineda A.A.V., Villafuerte M.V.E., Herrera M.O.G., Baasanjav B., Hachimi A., Elkhayari M., Dendane T., Subedi N.B., Pathak S.D., Manandhar M., Van Gulik L., Van Den Brink M., Van Vliet P., Gerretsen B., Van Den Berg L., De Haan M., Tuinstra B., Kuijpers P., Reijntjens J., Vermeijden J.W., Rinket M., Vanroest M., Reidinga A., Loef B., Dieperink W., Onrust M., Dormans T., Bormans L., Koopmans M., Gerritsen R.T., Van Den Elst A., Evers M., Oiting O., Wilting R., Ramaker B., van der Kuil M., Fijen J.-W., Haas L., De Lange D., Haringman J., Newby L., Gilder E., Hacking D., Dagooc R., Song R., Waibel H., Dawn F., Rapley J., Chadwick L., Chapman C., Crone P., Albrett J., Marko P., Goodson J., Browne T., Whitticase R., Davidson C., Judd H., Owens D., Onyeka T., Ugwu I., Ilesanmi R., Adejumo P.O., Owojuyigbe A., Adenekan A., Uba S., Chime C., Jibrin D., Sankey B.J., Adekola O., Olanipekun S., Shosolcheva M., Gievski V., Kartalov A., Naumovski F., Kuzmanovska B., Trposak A., Bogoevska-Miteva Z., Rosalia R., Olsen B.F., Sjobo B., Jensen K.D., Sykehus D., Johansen B.F., Straede E., Johansen E., Finnstrom I.J., Toellefsen A., Ostenjo H., Bjorgen H., Bratsberg B., Kristoffersen E., Skorstad E.M., Hansen S., Vullum S., Lunde G.A., Arntsen W., Lund M., Akselsen G.R., Monstad K.R., Stenset A., Haugom H., Monsen B., Hogvall L., Trudvang S., Galaaen B., Malmin S.K., Andersen M.H., Hargott R.F., Andersen Y., Steffenak E., Nyhus M., Meland B., Hashmi M., Rivas N., Maidana E., de Jesus Ortiz A., Cabral D.M.B., Simi M., Aponte C., Rivas J.C., Gill S., Garcia A., Alvarenga G., Cespedes L., Perez H., Moreira M.L., Canete F., Gonzalez R., Monges N., Coman M., Pederzani M., Franco N., Aganon F., Martinez R., Noblezada-Uy D., Ellazar C.G., Cerezo F.D., Palo J.E., Aperocho C.A.J., Isanan M., Tubacka M., Jasiewicz P., Czuczwar M., Borys M., 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M., Ripolles-Melchor J., Martinez-Hurtado E., Alvarez J.D., Arcas M.L.B., Gonzalez J.I.T., de la Ventana A.B.S., Calleja P.L.-A., Alvarez R.G., Zamora P.S., Guerrero A.O., Cosano R., Perez-Vacas J., Campos-Perez M., Barreiro E.M., Sanchez L.C., Diaz M.G., Jimenez R., Del Rio Cabajo L., Muriel D.S., Alonso H.F., Fernandez A.W., Pinan I.S., Albaiceta G.M., Fernandez M.C.I., Abos F.J.S., Monedero P., Chueca R.M., Aguirre L.G., Manosa S.C., Luque C.P., Calpe N., Losilla M.R., Fores M.T., Farre O., Fernandez O., del Rosario Villar Redondo M., Arteta Arteta D.S., Sanchez M.A.H., Espinosa C.P., Reyes L.M., Domenech L.C., Guillen C.V., Alvarez J.T., del Cotillo M., Barrueco-Francioni J.E., Conde B.B., Blanco M.P.S., Blasco M.L., Clement A.I., Hurtado C., Sanz L.C., Perez-Torres D., Prol-Silva E., Pereira J., Gonzalez I.A., Cano A.E., Nunez C.R., Fernadez I.L., Fernandez A.A.M., Del Bosque Diez R., Hilario B., Zalba-Etayo B., Pascual-Bielsa A., Banwarie P., Nahar D., van Axel A., Boedjawan N.N., Jansson E.B., Malvemyr A.-S., Johansson L., Sandberg U., Tingsvik C., Mattsson G., Lof G., Spangfors M., Ringdal M., Geijer S., Orvelius L., Hylen M., Lagerhall C., Akerman E., Hellkvist V.H., Mickelsson U., Wahlbom E., Larsson I.-M., Wallin E., Boroli F., Ory S., Jong M.L., Dullenkopf A., Lang M., Fleury Y., Maus M., Ben-Hamouda N., Fishman A., Hsu M.Y., Chang S.C., Trongtratul K., Sawawiboon C., Morakul S., Khwannimit B., Singh K., Ventour D., Figaro-Barclay D., Sankar-Maharaj S., Mebazaa M.S., Kamoun S., Elatrous S., Besbes L., Abroug F., Naija W., Elhechmi Y.Z., Sellami W., Hajjej Z., Merhabene T., Talik I., Kuscu O.O., Dilek O., Zerman A., Dal H.C., Turan S., Aydemir S., Yilmaz H., Calili D.K., Izdes S., Cengiz M., Gumus A., Tasdemir B., Kagnici A., Ay M., Ay S.A., Caliskan G., Akbas T., Balbay A.O., Efe S., Inal V., Elay G., Karabacak P., Ozserezli B., Senturk E., Demirkiran O., Bozbay S., Erdogan E., Akker M., Peker N., Ozgultekin A., Serin S.O., Turan C., Karaoren G., Goksu S., Karakurt S., Arikan H., Gul F., Cinel I., Kara I., Undar H.N., Bayraktar Y.S., Celik J.B., Tokur M.E., Aydin D.T., Yildiz I., Ozcan B., Erdivanli B., Eroglu A., Akdag D., Unlu N., Dungca A., Ali A., Thankamma B., Reyes P.E., John S., Rajendran A., Ahmad F.K.E., Smiley K.A., Hojden S., Miller M.T., Das Sasidharan Nair V., Antonio M.G.S., Qawasmeh K.A., Shawish S.A., Twiggs H., Rosado I., Babych V., Morren F., Young C., Vaughan-Jones N., Harris S., Burns K., Georgiev C., Shayamano R., Kerslake I., Creber P., Vochin A., O'Brien C., Caddell P., Hagan S., Hughes M., Torlinski T., Sherwin J., Kannan S., Markham A., Lebon R., Cupitt J., Cranshaw J., White N., Marriott V., Milner W., Groba C.B., Azoia J., Polgarova P., George S., Kapoor R., Lynch C., Fox N., Cranmer K., Llewellym T., Matthews K., Maltby L., Ibao J., Boulton K., Jarman R., Baxter K., Raj A.S., Moghal A., White J., Barrowcliffe S., Pulletz M., Ganeshalingam V., Baruah R., Baker H., Woods J., Ei P.P., Ogbeide V., Hayden P., Hughes J., Balasubramanian M., Salberg A., Saha R., Holmquist D., Derbyshire C., Smith N., Stones E., Ademokun J., Legorburo M.S., North S., Brett C., Jaundoo H., Craig J., Whiteley S., Howcroft C., Wilby L., Delve P., Shaw D., Williams K., Welters I.D., McMullen J., Brett S., Flores L., Trueman-Dawkins T., Templeton M., Adams J., Prowle J., Byers H., McDonnell A., Rose B.O., Reece-Anthony R., Mendes L., Vizcaychipi M., Bull R., Lacaden G., Santiago E., Delgado C.C., Farnell-Ward S., Thorpe E., Somerville J., Williams A., Cummings D., Derrick H., Brumwell S., Randell C., McCann N., Aves E., Berry G., Szakmany T., Gunter U., Pulak P., Sarkar N., Wright K., Gomes V., Jones J., Palfrey R., Camsooksai J., Lewis A., Eneas A., Tridente A., Barr L., Thomas B., Parkin E., Horner D., Frey C., Bench S., Baumber R., Broadhurst P., Jackson M., Williams L., Clark M., Paddle J., Bean S., Buckley S., Palfreeman C., Liu S., Allison N., Attwood B., Parsons P., Houghton V., Turner S.J., Higgins D., Bielskute E., Horrigan N., Jacob R., Habgood K., Zaki A., Collins A., Lord J., Ramiro C., Kubisz-Pudelko A., Kotze M., Williams H., Iovenko I., Tsarev A., Briva A., Mendez G., Napolitano L., Teig M., Rodriguez G.E., Ben-Jacob T., Potestio C., Eng T., Mahanes D., Khanna A., Duggal A., Nananmori M., Lois M., Karamchandani K., Bealer C., Barefield C., Terry D., Fivecoat P., Idowu O., Cata J., Clesi T., Peterson J., Hatton K., Dhaliwal J., Mueller D., Tao J., Eltorai A.S., Pastores S.M., Remor N., Salazar J., Barkas D., Joffe A., Barnes C., Sona C., Schallom M., Short J., Lorenzo J., Von Der Osten I., Borkowska M., Demarre L., Pleitinckx V., Xing C., Debue A.-S., Goller S., Larina E., Labeau, S. O., Blackwood, B., Brett, S. J., Deschepper, M., Francois, G., Honore, P. M., Khanna, A. K., Williams, G., Blot, S. I., Ribas, A. M., Telleria, V. M., Nogueira, P. C., Nafees, K. M. K., Reyes, A. G., Jensen, H. I., Adipa, F. E., Agoston, Z., Hashemian, S. M., Lee, S. -M., Abillama, F. F., Nor, B. M., Mazlan, M. Z., Sanchez-Hurtado, L., De lange, D., Ilesanmi, R. E., Ffarcsi, M. H., Hernandez, A. M., Schefold, J. C., Besbes, L. O., Minope, J. T. S., Rostello, O. F., Bartoli, J. R., Nocheretti, M. G., Escalante, R. G., Loudet, C. I., Gonzalez, A. L., Alvarez, G. A., Campos, P. A., Fonseca, I. P., Alvarez, G. M., Bascary, C. A., del Valle Gimenez, G., Bertoletti, F. P., Bonsignore, P. J. M., Fernandez, M. A., Leslie, G. D., Mclucas, A., Jacquet, L. -M., de Almeida, A. O., Jorge, S. A., Schmidt, R. C., Garcia, P. C., Ronchini, A. L. V., Manap, N. B. A., Laizner, A. M., Mcquirter, M., Kampayana, B. S., Sepulveda, M. I., Zamorano, M. J. F., Zhao, R. H., Hu, L. P., Jiao, Q. F., Wang, H. Y., Xia, C. J., Insu, L., Zhu, J. Y., Zhu, J. F., Huang, R. F., Wang, L. L., Song, J. H., Liu, X. M., Li, Z. S., Li, L. C., Zeng, J. M., Hu, X. C., Wang, R. X., Tak, P. S., Ho, S. W., Jiang, Q. X., Huang, L. P., Liu, X. L., Jiang, J. H., Gong, Y. Y., Lei, D. H., Bi, A. P., Zhao, H. M., Cao, Z. Q., Wu, S. F., Tian, X. F., Feng, Z. X., Liu, X. Z., Jiang, Z. X., Wang, G. X., Hu, R. L., Li, X. Q., Yu, Z. J., Yang, Y. X., Gama, L. M. S., Hernandez, J. S., Ochoa, M. -E., Reyes, A. J. G., Filipovic-Grcic, I., Vukovic, A., Pecenkovic, S., Suput, A., Radivojevic, R. C., Culjak, H., Adam, V. N., Pedersen, K. R., Kjaergard, I. E., Kodal, A. M., Hansen, T. C. B., Pedersen, A. S. B., Thomsen, T. D., Frandsen, T. M., Bliksted, I. A., Tamayo, L. M., Tutillo, D. R. M., Hurtado, C. V., Garcia, M. F., Kutimets, M., Lofqvist, C., Sakki, J. -K., Valta, M. A., Plantefeve, G., Deserts, M. D., Gunther, S. C., Timsit, J. -F., Farkas, J. -C., Bosl, K., Schuppel, S., Stubner, A., Osei, I. P., Kusi-Appiah, A. -C., Yakubu, Y. H., Patsiou, E. -C., Stalika, K. M. M., Enamorado, J. E., Jonasdottir, R. J., Lestari, M. I., Finn, D. O. C. R., Mcpherson, S., Ghioldi, D. M., Bruno, A. V., Maggiore, S. M., Volta, C. A., Taibi, M. R., Tranello, F. P., Giusti, G. D., Martin, M. A., Correia, M. C., Kim, J. H., Kim, K. C., Bae, J. -M., Park, S. Y., Park, T. S., Lee, H. B., Kim, S. C., Chee, H. K., Huh, J. W., Sim, Y. S., Ahn, J. -J., Kang, B. J., Lee, W. -Y., Lee, S. J., Feghaly, M. E., Belkhair, W. A., Tababa, O. W. E., Alkhumsi, S. I. R., Alshrif, A. I., Aboufray, A. A., Triki, A. R., Zahra, H. B., Al-Alawi, M. M. S., Ghula, M. A. A., Bahrin, L. K. K., Deva, S. R., Rahim, A. H. A., Hassan, W. N. W., Ismail, W. N. W., Ali, M. N., Khoo, T. M., Samat, N. M., Tong, J. M. G., Adib, N. A. N., Nor, M. B. M., Sulaiman, S. R., Foong, K. W., Hua, N. P., Zermeno, J. M., Nava, C. L. L., Nandyelly, S. J. R., Sanchez-Hurtado, L. A., Nava, L. P. A., Herrera, J. G., de Anda, G. F. V., Namendys-Silva, S. A., Romero-Gonzalez, J. P., Sosa, M. A., de Molina Serrano, J. I. R., Iburrigarro, S. R., Padilla, N. R. C., Pineda, A. A. V., Villafuerte, M. V. E., Herrera, M. O. G., Subedi, N. B., Pathak, S. D., Vermeijden, J. W., Gerritsen, R. T., Fijen, J. -W., Adejumo, P. O., Sankey, B. J., Olsen, B. F., Jensen, K. D., Johansen, B. F., Finnstrom, I. J., Skorstad, E. M., Lunde, G. A., Akselsen, G. R., Monstad, K. R., Hogvall, L., Malmin, S. K., Andersen, M. H., Hargott, R. F., de Jesus Ortiz, A., Cabral, D. M. B., Rivas, J. C., Moreira, M. L., Ellazar, C. G., Cerezo, F. D., Palo, J. E., Aperocho, C. A. J., Figueiredo, M. F., Pinheiro, C. M., Rita, C. S., Feranandes, A. M., Pinto, V. M. V., Bispo, B. M., Lima, A., Alsheikhly, A. S., Guran, C. T., Filipescu, D. C., Scutariu, M. A., Ebaid, M. S., Velickovic, D., Rajkovic, M., Stanojevic, M., Turcan, A., Lancaricova, D., Yeni, N. P., Syed, M. R., Navarro, J. A., De Pablo, A. M., Llinas, A. A., Lajara, M. A. G., Nieto, M. V., Pena, J. M. G., Gorgolas, M. C., Isasi, M. A., Salva-Costa, V., Garzon-Tovar, C., Olivares, P. G., de Ceballos, J. P. G., Polo, A. B. C., del Mar Diaz Salcedo, M., Alvarez, J. D., Arcas, M. L. B., Gonzalez, J. I. T., de la Ventana, A. B. S., Calleja, P. L. -A., Alvarez, R. G., Zamora, P. S., Guerrero, A. O., Barreiro, E. M., Sanchez, L. C., Diaz, M. G., Muriel, D. S., Alonso, H. F., Fernandez, A. W., Pinan, I. S., Albaiceta, G. M., Fernandez, M. C. I., Abos, F. J. S., Chueca, R. M., Aguirre, L. G., Manosa, S. C., Luque, C. P., Losilla, M. R., Fores, M. T., del Rosario Villar Redondo, M., Arteta Arteta, D. S., Sanchez, M. A. H., Espinosa, C. P., Reyes, L. M., Domenech, L. C., Guillen, C. V., Alvarez, J. T., del Cotillo, M., Barrueco-Francioni, J. E., Conde, B. B., Blanco, M. P. S., Blasco, M. L., Clement, A. I., Sanz, L. C., Gonzalez, I. A., Cano, A. E., Nunez, C. R., Fernadez, I. L., Fernandez, A. A. M., Boedjawan, N. N., Jansson, E. B., Malvemyr, A. -S., Lof, G., Spangfors, M., Lagerhall, C., Akerman, E., Hellkvist, V. H., Larsson, I. -M., Jong, M. L., Hsu, M. Y., Chang, S. C., Mebazaa, M. S., Elhechmi, Y. Z., Kuscu, O. O., Dal, H. C., Calili, D. K., Izdes, S., Gumus, A., Tasdemir, B., Kagnici, A., Ay, S. A., Balbay, A. O., Ozserezli, B., Senturk, E., Serin, S. O., Gul, F., Cinel, I., Undar, H. N., Bayraktar, Y. S., Celik, J. B., Tokur, M. E., Aydin, D. T., Yildiz, I., Ozcan, B., Akdag, D., Unlu, N., Reyes, P. E., Ahmad, F. K. E., Smiley, K. A., Miller, M. T., Antonio, M. G. S., Qawasmeh, K. A., Shawish, S. A., Groba, C. B., Raj, A. S., Ei, P. P., Legorburo, M. S., Welters, I. D., Mcmullen, J., Mcdonnell, A., Rose, B. O., Delgado, C. C., Mccann, N., Turner, S. J., Rodriguez, G. E., Eltorai, A. S., Pastores, S. M., Demarre, L., and Debue, A. -S.
Subjects: Male, Original, medicine.medical_treatment, artificial, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Pressure ulcer, law.invention, Decubitus epidemiology, ICU, Morbidity, Mortality, Outcome, Pressure injury, Risk factors, Adult, Aged, Hospital Mortality, Humans, Patient Discharge, Prevalence, Risk Factors, Intensive Care Units, Respiration, Artificial, 0302 clinical medicine, decubitus epidemiology, pressure injury, pressure ulcer, outcome, risk factors, morbidity, mortality, law, Medicine and Health Sciences, adults, Medicine, Simplified Acute Physiology Score, icu, ziekenhuissterfte, Immunodeficiency, intensive care, European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, mannen, volwassenen, COST, Intensive care unit, STATE, ULCERS, Underweight, medicine.symptom, Life Sciences & Biomedicine, Human, medicine.medical_specialty, risicofactoren, Decubitus epidemiology, ICU, Pressure injury, Pressure ulcer, Outcome, Risk factors, Morbidity, Mortality, pressure injuries, Intensive Care Unit, prevalentie, NO, 1117 Public Health and Health Services, DecubICUs Study Team, 03 medical and health sciences, Critical Care Medicine, Anesthesiology, General & Internal Medicine, Health Sciences, ouderen, Mechanical ventilation, Science & Technology, business.industry, decubitus, Risk Factor, 030208 emergency & critical care medicine, 1103 Clinical Sciences, Odds ratio, medicine.disease, Emergency & Critical Care Medicine, Confidence interval, 030228 respiratory system, Emergency medicine, kunstmatige ademhaling, RISK-FACTORS, business, respiration
Abstract: Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347, Funder: Flemish Society for Critical Care Nurses, Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.
Published: 2021
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32. Response to: Comment on: Postoperative opioid administration characteristics associated with opioid-induced respiratory depression: Results from the PRODIGY trial

Author: Maria Wittmann, Morgan Le Guen, Wolfgang Buhre, Ashish Khanna, Fabio Di Piazza, Sergio D. Bergese, Richard D. Urman, Leif Saager, Frank J. Overdyk, Anesthesiologie, MUMC+: MA Anesthesiologie (9), and RS: MHeNs - R3 - Neuroscience
Subjects: Anesthesiology and Pain Medicine, Opioid, business.industry, Anesthesia, medicine, Respiratory system, business, Administration (government), Depression (differential diagnoses), medicine.drug
Published: 2021

33. Practice Patterns and Variability in Intraoperative Opioid Utilization: A Report From the Multicenter Perioperative Outcomes Group

Author: Chad M. Brummett, Karen B. Domino, Anik Sinha, Marcel E. Durieux, Karen L. Posner, Sachin Kheterpal, Nathan L. Pace, Ami R. Stuart, Kai Kuck, Leif Saager, Bhiken I. Naik, and Michelle T. Vaughn
Subjects: Adult, Male, Longitudinal study, Analgesic, Remifentanil, Neuraxial blockade, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Interquartile range, Outcome Assessment, Health Care, medicine, Humans, Pain Management, 030212 general & internal medicine, Dosing, Longitudinal Studies, Practice Patterns, Physicians', Retrospective Studies, Pain, Postoperative, Morphine, business.industry, Bayes Theorem, Perioperative, Middle Aged, 3. Good health, Analgesics, Opioid, Anesthesiology and Pain Medicine, Opioid, Anesthesia, Surgical Procedures, Operative, Multivariate Analysis, Female, Analgesia, business, medicine.drug
Abstract: Background Opioids remain the primary mode of analgesia intraoperatively. There are limited data on how patient, procedural, and institutional characteristics influence intraoperative opioid administration. The aim of this retrospective, longitudinal study from 2012 to 2016 was to assess how intraoperative opioid dosing varies by patient and clinical care factors and across multiple institutions over time. Methods Demographic, surgical procedural, anesthetic technique, and intraoperative analgesia data as putative variables of intraoperative opioid utilization were collected from 10 institutions. Log parenteral morphine equivalents (PME) was modeled in a multivariable linear regression model as a function of 15 covariates: 3 continuous covariates (age, anesthesia duration, year) and 12 factor covariates (peripheral block, neuraxial block, general anesthesia, emergency status, race, sex, remifentanil infusion, major surgery, American Society of Anesthesiologists [ASA] physical status, non-opioid analgesic count, Multicenter Perioperative Outcomes Group [MPOG] institution, surgery category). One interaction (year by MPOG institution) was included in the model. The regression model adjusted simultaneously for all included variables. Comparison of levels within a factor were reported as a ratio of medians with 95% credible intervals (CrI). Results A total of 1,104,324 cases between January 2012 and December 2016 were analyzed. The median (interquartile range) PME and standardized by weight PME per case for the study period were 15 (10-28) mg and 200 (111-347) μg/kg, respectively. As estimated in the multivariable model, there was a sustained decrease in opioid use (mean, 95% CrI) dropping from 152 (151-153) μg/kg in 2012 to 129 (129-130) μg/kg in 2016. The percent of variability in PME due to institution was 25.6% (24.8%-26.5%). Less opioids were prescribed in men (130 [129-130] μg/kg) than women (144 [143-145] μg/kg). The men to women PME ratio was 0.90 (0.89-0.90). There was substantial variability in PME administration among institutions, with the lowest being 80 (79-81) μg/kg and the highest being 186 (184-187) μg/kg; this is a PME ratio of 0.43 (0.42-0.43). Conclusions We observed a reduction in intraoperative opioid administration over time, with variability in dose ranging between sexes and by procedure type. Furthermore, there was substantial variability in opioid use between institutions even when adjusting for multiple variables.
Published: 2021

34. Role of total lung stress on the progression of early COVID-19 pneumonia

Author: Mattia Busana, Paola Palermo, Federica Romitti, Simone Gattarello, Emanuele Giola, Davide Chiumello, Tommaso Pozzi, Irene Steinberg, Konrad Meissner, John J. Marini, Leif Saager, Peter Herrmann, Stefano Centanni, Luigi Camporota, Michael Quintel, Luciano Gattinoni, Stefano Lazzari, Michela Palumbo, Silvia Coppola, and Stefano Roli
Subjects: Lung stress, ARDS, medicine.medical_specialty, Original, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Computed tomography scan, Gastroenterology, Hypoxemia, Cohort Studies, Mechanical ventilation, Internal medicine, medicine, Humans, Continuous positive airway pressure, Prospective Studies, Prospective cohort study, Lung, Ventilation-induced lung injury, business.industry, SARS-CoV-2, COVID-19, Correction, medicine.disease, respiratory tract diseases, Pneumonia, medicine.anatomical_structure, Breathing, medicine.symptom, business, Non-invasive respiratory support
Abstract: Purpose We investigated if the stress applied to the lung during non-invasive respiratory support may contribute to the coronavirus disease 2019 (COVID-19) progression. Methods Single-center, prospective, cohort study of 140 consecutive COVID-19 pneumonia patients treated in high-dependency unit with continuous positive airway pressure (n = 131) or non-invasive ventilation (n = 9). We measured quantitative lung computed tomography, esophageal pressure swings and total lung stress. Results Patients were divided in five subgroups based on their baseline PaO2/FiO2 (day 1): non-CARDS (median PaO2/FiO2 361 mmHg, IQR [323–379]), mild (224 mmHg [211–249]), mild-moderate (173 mmHg [164–185]), moderate-severe (126 mmHg [114–138]) and severe (88 mmHg [86–99], p
Published: 2021

35. Incidence, risk factors, and consequences of residual neuromuscular block in the United States: The prospective, observational, multicenter RECITE-US study

Author: Tong J. Gan, Roy Soto, Pedro Paulo Tanaka, Yiliam F. Rodriguez-Blanco, Leif Saager, Tricia A. Meyer, Harold S. Minkowitz, Eric M. Maiese, Lori D. Bash, Scott B. Groudine, Beverly K. Philip, and Olaf Heisel
Subjects: Adult, Male, Anesthesia, General, Delayed Emergence from Anesthesia, Body Mass Index, Young Adult, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, 030202 anesthesiology, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, Aged, 80 and over, Neuromuscular Blockade, business.industry, Incidence, Middle Aged, Neuromuscular monitoring, Neostigmine, United States, Neuromuscular Nondepolarizing Agents, Anesthesiology and Pain Medicine, Elective Surgical Procedures, Anesthesia, Female, Cholinesterase Inhibitors, Neuromuscular Monitoring, business, Elective Surgical Procedure, Cohort study, medicine.drug, Abdominal surgery
Abstract: To determine the incidence burden and associated risk factors of residual neuromuscular block (rNMB) during routine U.S. hospital care.Blinded multicenter cohort study.Operating and recovery rooms of ten community and academic U.S. hospitals.Two-hundred fifty-five adults, ASA PS 1-3, underwent elective abdominal surgery with general anesthesia and ≥1 dose of non-depolarizing neuromuscular blocking agent (NMBA) for endotracheal intubation and/or maintenance of NMB between August 2012 and April 2013.TOF measurements using acceleromyography were performed on patients already receiving routine anesthetic care for elective open or laparoscopic abdominal surgery. Measurements allowed assessment of the presence of residual neuromuscular block (rNMB), defined as a train-of-four (TOF) ratio0.9 at tracheal extubation. We recorded patient and procedural characteristics and assessed TOF ratios (T4/T1) at various times throughout the procedure and at tracheal extubation. Differences in patient and clinical characteristics were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Multivariate logistic regression assessed risk factors associated with rNMB at extubation.Most of the study population, 64.7% (n = 165) had rNMB (TOF ratio 0.9), among them, 31.0% with TOF ratio0.6. Among those receiving neostigmine and/or qualitative peripheral nerve stimulation per clinical decision, 65.0% had rNMB. After controlling for confounders, we observed male gender (odds ratio: 2.60, P = 0.008), higher BMI (odds ratio: 1.04/unit, P = 0.043), and surgery at a community hospital (odds ratio: 3.15, P = 0.006) to be independently associated with increased odds of rNMB.Assessing TOF ratios blinded to the care team, we found that the majority of patients (64.7%) in this study had rNMB at tracheal extubation, despite neostigmine administration and qualitative peripheral nerve stimulation used for routine clinical care. Qualitative neuromuscular monitoring and clinical judgement often fails to detect rNMB after neostigmine reversal with potential severe consequences to the patient. Our data suggests that clinical care could be improved by considering quantitative neuromuscular monitoring for routine care.
Published: 2019

36. Correction to: Role of total lung stress on the progression of early COVID‑19 pneumonia

Author: Silvia Coppola, Davide Chiumello, Mattia Busana, Emanuele Giola, Paola Palermo, Tommaso Pozzi, Irene Steinberg, Stefano Roli, Federica Romitti, Stefano Lazzari, Simone Gattarello, Michela Palumbo, Peter Herrmann, Leif Saager, Michael Quintel, Konrad Meissner, Luigi Camporota, John J. Marini, Stefano Centanni, and Luciano Gattinoni
Subjects: Critical Care and Intensive Care Medicine
Published: 2021

37. Do It Often, Do It Better: Association Between Pairs of Experienced Subspecialty Anesthesia Caregivers and Postoperative Outcomes. A Retrospective Observational Study

Author: Daniel I. Sessler, Kurt Ruetzler, Alparslan Turan, Kamal Maheshwari, Jing You, Edward J. Mascha, Yuwei Qiu, Ilker Ince, Leif Saager, and Barak Cohen
Subjects: Time Factors, Risk Assessment, Gee, Odds, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, 030202 anesthesiology, Risk Factors, Medicine, Humans, Hospital Mortality, Generalized estimating equation, Retrospective Studies, Patient Care Team, Intraoperative Care, business.industry, Retrospective cohort study, Odds ratio, Length of Stay, Confidence interval, Anesthesiologists, Anesthesiology and Pain Medicine, Treatment Outcome, Anesthesia, Surgical Procedures, Operative, Propensity score matching, Observational study, Clinical Competence, business, 030217 neurology & neurosurgery, Specialization
Abstract: BACKGROUND Anesthesiologists typically care for patients having a broad range of procedures. Outcomes might be improved when care is provided by caregivers experienced in particular types of surgery. We tested the hypothesis that intraoperative care provided by pairs of anesthesia caregivers having significant experience with a particular type of surgery reduces a composite of in-hospital death and 6 serious complications, including bleeding, cardiac, gastrointestinal, infectious, respiratory, and urinary complications, compared to care provided by pairs of anesthesia caregivers with less experience. METHODS We included patients having surgery lasting at least 30 minutes. Using cluster analysis, attending anesthesiologists, and Certified Registered Nurse Anesthetists (CRNAs) were identified as experienced or inexperienced caregivers for each type of surgery at the case level. We then compared surgeries for which anesthesia was provided by a pair of experienced caregivers versus a pair of inexperienced caregivers on our composite outcome. We estimated the average relative effect (ie, the exponentiated average log odds ratio) of receiving anesthesia from an experienced versus inexperienced caregiver pair across the 7 components of the composite outcome using a generalized estimating equation (GEE) model to adjust for between-component correlation and with inverse propensity score weighing to adjust for potential confounding from a host of variables. RESULTS A total of 8968 patients who received anesthesia care by an experienced pair were compared with 25,361 patients who received care from an inexperienced pair, adjusting for potential confounding. The incidence of composite complications (ie, any component event) was 7.6% (677/8968) for experienced pairs and 12% (2976/25,361) for inexperienced pairs (P < .001). Care by experienced pairs of caregivers was associated with lower odds of the composite outcome with an estimated average relative effect odds ratio across the individual components of 0.61 (95% confidence interval [CI], 0.54-0.71), P < .001. Among the 7 components of the primary outcome, experienced pairs of providers had significantly lower estimated odds of bleeding, infection, and mortality. CONCLUSIONS Anesthesia care by experienced pairs was associated with fewer bleeding complications, fewer infections, shorter hospitalization, and reduced in-hospital mortality.
Published: 2021

38. ID: 3523898 ADVERSE EVENTS WITH GENERAL ANESTHESIA VERSUS SEDATION WITHOUT PLANNED INTUBATION FOR ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY: A MULTICENTER OBSERVATIONAL STUDY

Author: Chen Liang, Sekar S. Bhavani, Linda C. Cummings, John J. Vargo, Leif Saager, Zachary L. Smith, Kenneth C. Cummings, and Edward J. Mascha
Subjects: Endoscopic retrograde cholangiopancreatography, medicine.diagnostic_test, business.industry, Sedation, medicine.medical_treatment, Gastroenterology, Anesthesia, Medicine, Intubation, Radiology, Nuclear Medicine and imaging, Observational study, medicine.symptom, business, Adverse effect
Published: 2021

39. Utilization Patterns of Perioperative Neuromuscular Blockade Reversal in the United States: A Retrospective Observational Study From the Multicenter Perioperative Outcomes Group

Author: Leif Saager, Michael R. Mathis, Timur Dubovoy, Graciela Mentz, Sachin Kheterpal, Steven R. Kapeles, Michelle T. Vaughn, Nirav Shah, and Douglas A. Colquhoun
Subjects: Adult, Male, medicine.medical_specialty, Sugammadex, Article, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, 030202 anesthesiology, Internal medicine, medicine, Humans, Perioperative Period, Aged, Retrospective Studies, Heart Failure, Dose-Response Relationship, Drug, business.industry, Age Factors, Retrospective cohort study, Perioperative, Odds ratio, Middle Aged, Thoracic Surgical Procedures, Confidence interval, United States, Anesthesiology and Pain Medicine, Treatment Outcome, Quartile, Cardiothoracic surgery, Neuromuscular Blockade, Observational study, Female, Neuromuscular Blocking Agents, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: BACKGROUND: Following the introduction of sugammadex to the United States clinical practice, scarce data are available to understand its utilization patterns. This study aimed to characterize patient, procedure, and provider factors associated with sugammadex administration in the US patients. METHODS: This retrospective observational study was conducted across 24 Multicenter Perioperative Outcomes Group institutions in the United States with sugammadex on formulary at the time of the study. All American Society of Anesthesiologists (ASA) physical status 1-4 adults undergoing noncardiac surgery from 2014 to 2018 receiving neuromuscular blockade were eligible. The study established three periods based on the date of first documented sugammadex use at each institution: the pre-sugammadex period, 0-6 month transitional period, and 6+ months post-sugammadex period. The primary outcome was reversal using sugammadex during the post-sugammadex period - defined as 6 months after sugammadex was first utilized at each institution. A multivariable mixed-effects logistic regression model controlling for institution was developed to assess patient, procedure, and provider factors associated with sugammadex administration. RESULTS: A total of 934,798 cases met inclusion criteria. Following the 6-month transition period, sugammadex was used on average in 40.0% (95% CI 39.8%-40.2%) of cases receiving neuromuscular blockade. Multivariable analysis demonstrated sugammadex use to be associated with train-of-four count of 0-1 (adjusted odds ratio 4.06, 95% CI 3.83-4.31) or 2 (2.45, 2.29-2.62) versus 3-4 twitches before reversal; the amount of neuromuscular blockade (NMB) administered (3.01, 2.88-3.16) for the highest Effective Dose 95 quartile compared to the lowest quartile; advanced age (1.83, 1.71-1.95) compared to age less than 41; male sex (1.36, 1.32-1.39) compared to female sex; major thoracic surgery (1.26, 1.13-1.39); congestive heart failure (1.17, 1.07-1.28); and ASA 3 or 4 (1.13, 1.10-1.16) versus ASA 1 or 2. CONCLUSIONS: Our data demonstrates broad early clinical adoption of sugammadex following Food and Drug Administration approval. Sugammadex is used preferentially in cases with higher degrees of neuromuscular blockade prior to reversal and in patients with greater burden of comorbidities and known risk factors for residual blockade or pulmonary complications.
Published: 2020

40. Prediction of opioid-induced respiratory depression on inpatient wards using continuous capnography and oximetry

Author: Sabry Ayad, Susan J. Dempsey, Hiroshi Morimatsu, Alberto A. Uribe, Maria Wittmann, Carlos Tornero, Luca Brazzi, Morgan Le Guen, Carla R. Jungquist, Robert C. McIntyre, Vanessa Moll, Lian Kah Ti, Sergio D. Bergese, Wolfgang Buhre, Ashish Khanna, Richard D. Urman, Paola Di Stefano, Toby N. Weingarten, Frank J. Overdyk, Albert Dahan, Roop Kaw, Daniel I. Sessler, Leif Saager, Dennis Auckley, Frank Schramm, Shoichi Uezono, Roy Soto, Simon C. Lee, MUMC+: Centrum voor Acute en Kritieke Zorg (3), Anesthesiologie, MUMC+: MA Anesthesiologie (9), RS: MHeNs - R3 - Neuroscience, University of Zurich, and Khanna, Ashish K
Subjects: medicine.medical_specialty, Respiratory rate, 10216 Institute of Anesthesiology, MODELS, Vital signs, 610 Medicine & health, PATIENT, VALIDATION, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Interquartile range, POSTOPERATIVE HYPOXEMIA, medicine, Original Clinical Research Report, Prospective cohort study, Depression (differential diagnoses), INDEX, RISK, Capnography, PAIN MANAGEMENT, OUTCOMES, medicine.diagnostic_test, Featured Articles, business.industry, Apnea, 3. Good health, Anesthesiology and Pain Medicine, Predictive value of tests, SAFETY, Emergency medicine, 2703 Anesthesiology and Pain Medicine, medicine.symptom, ADVERSE EVENTS, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Opioid-related adverse events are a serious problem in hospitalized patients. Little is known about patients who are likely to experience opioid-induced respiratory depression events on the general care floor and may benefit from improved monitoring and early intervention. The trial objective was to derive and validate a risk prediction tool for respiratory depression in patients receiving opioids, as detected by continuous pulse oximetry and capnography monitoring. METHODS: PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) was a prospective, observational trial of blinded continuous capnography and oximetry conducted at 16 sites in the United States, Europe, and Asia. Vital signs were intermittently monitored per standard of care. A total of 1335 patients receiving parenteral opioids and continuously monitored on the general care floor were included in the analysis. A respiratory depression episode was defined as respiratory rate = 60 mm Hg for >= 3 minutes; apnea episode lasting >30 seconds; or any respiratory opioid-related adverse event. A risk prediction tool was derived using a multivariable logistic regression model of 46 a priori defined risk factors with stepwise selection and was internally validated by bootstrapping. RESULTS: One or more respiratory depression episodes were detected in 614 (46%) of 1335 general care floor patients (43% male; mean age, 58 +/- 14 years) continuously monitored for a median of 24 hours (interquartile range [IQR], 17-26). A multivariable respiratory depression prediction model with area under the curve of 0.740 was developed using 5 independent variables: age >= 60 (in decades), sex, opioid naivety, sleep disorders, and chronic heart failure. The PRODIGY risk prediction tool showed significant separation between patients with and without respiratory depression (P< .001) and an odds ratio of 6.07 (95% confidence interval [CI], 4.44-8.30;P< .001) between the high- and low-risk groups. Compared to patients without respiratory depression episodes, mean hospital length of stay was 3 days longer in patients with >= 1 respiratory depression episode (10.5 +/- 10.8 vs 7.7 +/- 7.8 days;P< .0001) identified using continuous oximetry and capnography monitoring. CONCLUSIONS: A PRODIGY risk prediction model, derived from continuous oximetry and capnography, accurately predicts respiratory depression episodes in patients receiving opioids on the general care floor. Implementation of the PRODIGY score to determine the need for continuous monitoring may be a first step to reduce the incidence and consequences of respiratory compromise in patients receiving opioids on the general care floor.
Published: 2020

41. Risk of Major Complications after Perioperative Norepinephrine Infusion through Peripheral Intravenous Lines in a Multicenter Study

Author: Ruth Cassidy, Philipp Lirk, Wilton A. van Klei, Carlo Pancaro, Sachin Kheterpal, Dave Vittali, Leif Saager, Fabian O. Kooij, Wietze Pasma, Nirav Shah, Markus W. Hollmann, Anesthesiology, ACS - Heart failure & arrhythmias, and ACS - Microcirculation
Subjects: business.industry, Drug Extravasation, Retrospective cohort study, Perioperative, Extravasation, Peripheral, Norepinephrine (medication), 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030202 anesthesiology, Anesthesia, Peripheral venous catheter, Medicine, business, Adverse effect, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Continuous infusions of norepinephrine to treat perioperative hypotension are typically administered through a central venous line rather than a peripheral venous catheter to avoid the risk of localized tissue necrosis in case of drug extravasation. There is limited literature to estimate the risk of skin necrosis when peripheral norepinephrine is used to counteract anesthesia-associated hypotension in elective surgical cases. This study aimed to estimate the rate of occurrence of drug-related adverse effects, including skin necrosis requiring surgical management when norepinephrine peripheral extravasation occurs. Methods This retrospective cohort study used the perioperative databases of the University Hospitals in Amsterdam and Utrecht, the Netherlands, to identify surgical patients who received norepinephrine peripheral intravenous infusions (20 µg/mL) between 2012 and 2016. The risk of drug-related adverse effects, including skin necrosis, was estimated. Particular care was taken to identify patients who needed plastic surgical or medical attention secondary to extravasation of dilute, peripheral norepinephrine. Results A total of 14,385 patients who received norepinephrine peripheral continuous infusions were identified. Drug extravasation was observed in 5 patients (5/14,385 = 0.035%). The 95% confidence interval (CI) for infusion extravasation was 0.011%-0.081%, indicating an estimated risk of 1-8 events per every 10,000 patients. There were zero related complications requiring surgical or medical intervention, resulting in a 95% CI of 0%-0.021% and indicating a risk of approximately 0-2 events per 10,000 patients. Conclusions In the current database analysis, no significant association was found between the use of peripheral intravenous norepinephrine infusions and adverse events.
Published: 2020

42. An observational study of end-tidal carbon dioxide trends in general anesthesia

Author: Michael F. Aziz, William C. Paganelli, Judith A. R. van Waes, Jonathan P. Wanderer, Daniel L. Helsten, Wilton A. van Klei, Sachin Kheterpal, Annemarie Akkermans, Amy Shanks, Leif Saager, Aleda Thompson, Linda M. Peelen, and Daniel A. Biggs
Subjects: Adult, Male, medicine.medical_specialty, Databases, Factual, Intraclass correlation, Anesthesia, General, Neurosurgical Procedures, Reports of Original Investigations, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Robotic Surgical Procedures, Capnography, 030202 anesthesiology, Interquartile range, Anesthesiology, medicine, Humans, 030212 general & internal medicine, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Retrospective cohort study, General Medicine, Perioperative, Carbon Dioxide, Middle Aged, Confidence interval, Anesthesiology and Pain Medicine, Anesthesia, Female, Laparoscopy, Observational study, business
Abstract: Purpose Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO2) levels in surgical patients, there is still insufficient data to formulate guidelines for ideal intraoperative ETCO2 targets. As it is unclear which intraoperative ETCO2 levels are currently used and whether these levels have changed over time, we investigated the practice pattern using the Multicenter Perioperative Outcomes Group database. Methods This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO2 thresholds (< 28, < 35, < 45, and > 45 mmHg). Additionally, a median ETCO2 was studied. A Kruskal-Wallis test was used to analyse differences between years. Random-effect multivariable logistic regression models were constructed to study variability. Results Both TWA-AUC and median ETCO2 showed a minimal increase in ETCO2 over time, with a median [interquartile range] ETCO2 of 33 [31.0–35.0] mmHg in 2008 and 35 [33.0–38.0] mmHg in 2016 (P
Published: 2018

43. The Association Between Timing of Routine Preoperative Blood Testing and a Composite of 30-Day Postoperative Morbidity and Mortality

Author: Kurt Ruetzler, Leif Saager, Amanda J. Naylor, Yehoshua N Schacham, Peirong Lin, Daniel I. Sessler, and Jing You
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Databases, Factual, Risk Assessment, Preoperative care, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, 030202 anesthesiology, Anesthesiology, Preoperative Care, medicine, Humans, Registries, 030212 general & internal medicine, Elective surgery, Aged, Retrospective Studies, Hematologic Tests, business.industry, Incidence, Incidence (epidemiology), Retrospective cohort study, Odds ratio, Middle Aged, United States, Confidence interval, Surgery, Treatment Outcome, Anesthesiology and Pain Medicine, Surgical Procedures, Operative, Predictive value of tests, Female, business
Abstract: Background Laboratory testing is a common component of preanesthesia evaluation and is designed to identify medical abnormalities that might otherwise remain undetected. While blood testing might optimally be performed shortly before surgery, it is often done earlier for practical reasons. We tested the hypothesis that longer periods between preoperative laboratory testing and surgery are associated with increased odds of having a composite of 30-day morbidity and mortality. Methods We obtained preoperative data from 2,320,920 patients in the American College of Surgeons National Surgical Quality Improvement Program who were treated between 2005 and 2012. Our analysis was restricted to relatively healthy patients with American Society of Anesthesiology physical status I-II who had elective surgery and normal blood test results (n = 235,010). The primary relationship of interest was the odds of 30-day morbidity and mortality as a function of delay between preoperative testing and surgery. A multivariable logistic regression model was used for the 10 pairwise comparisons among the 5 laboratory timing groups (laboratory blood tests within 1 week of surgery; 1-2 weeks; 2-4 weeks; 1-2 months; and 2-3 months) on 30-day morbidity, adjusting for any imbalanced baseline covariables and type of surgery. Results A total of 4082 patients (1.74%) had at least one of the component morbidities or died within 30-days after surgery. The observed incidence (unadjusted) was 1.7% when the most recent laboratory blood tests measured within 1 week of surgery, 1.7% when it was within 1-2 weeks, 1.8% when it was within 2-4 weeks, 1.7% when it was between 1 and 2 months, and 2.0% for patients with most recent laboratory blood tests measured 2-3 months before surgery. None of the values within 2 months differed significantly: estimated odds ratios for patients within blood tested within 1 week were 1.00 (99.5% confidence interval, 0.89-1.12) as compared to 1-2 weeks, 0.88 (0.77-1.00) for 2-4 weeks, and 0.95 (0.79-1.14) for 1-2 months, respectively. The estimated odds ratio comparing 1-2 weeks to each of 2-4 weeks and 1-2 months were 0.88 (0.76-1.03) and 0.95 (0.78-1.16), respectively. Blood testing 2-3 months before surgery was associated with increased odds of outcome compared to patients whose most recent test was within 1 week (P = .002) and 1-2 weeks of the date of surgery. Conclusions In American Society of Anesthesiologists physical status I and II patients, risk of 30-day morbidity and mortality was not different with blood testing up to 2 months before surgery, suggesting that it is unnecessary to retest patients shortly before surgery.
Published: 2018

44. Early Surgery Confers 1-Year Mortality Benefit in Hip-Fracture Patients

Author: Kamal Maheshwari, Alparslan Turan, Jing You, Andrea Kurz, Jeffrey Planchard, Leif Saager, Wael Ali Sakr, Jaiben George, and Carlos A. Higuera-Rueda
Subjects: Male, medicine.medical_specialty, Time Factors, MEDLINE, Logistic regression, Time-to-Treatment, Odds, 03 medical and health sciences, 0302 clinical medicine, Fracture Fixation, Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, 030212 general & internal medicine, Stroke, Aged, Ohio, Aged, 80 and over, 030222 orthopedics, Hip fracture, Hip Fractures, business.industry, General Medicine, Evidence-based medicine, Odds ratio, Prognosis, medicine.disease, United States, Female, Surgery, Electronic data, business
Abstract: Background To evaluate the relationship between surgical timing and 1-year mortality in patients requiring hip fracture repair. Methods We analyzed all 720 patients (>65 years) who had hip fracture surgery between March 2005 and February 2015, identifying patients by ICD-9 diagnosis and procedure codes using electronic data query. Mortality data were obtained from the institutional database, state and Social Security Death Indices. The relationship between surgical timing (defined as the interval from admission to the start of surgery) and 1-year mortality was assessed using a multivariable logistic regression, adjusting for baseline clinical status and surgical factors. Results Among the 720 patients, 159 patients (22%) died within 1 year. The median time from admission to surgery was 30 hours. A linear relationship between the surgical timing and 1-year mortality was demonstrated. Delaying surgery was significantly associated with increased 1-year mortality, odds ratio 1.05 (95% CI: 1.02-1.08) per 10-hour delay (P = 0.001). Conclusions A linear relationship was observed between surgical timing and 1-year mortality. Each 10-hour delay from admission to surgery was associated with an estimated 5% higher odds of 1-year mortality. Therefore, we suggest that hip fractures should be treated urgently similar to other time-sensitive pathology such as stroke and myocardial ischemia. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Published: 2018

45. Postoperative opioid administration characteristics associated with opioid-induced respiratory depression: Results from the PRODIGY trial

Author: Morgan Le Guen, Maria Wittmann, Wolfgang Buhre, Ashish Khanna, Richard D. Urman, Leif Saager, Frank J. Overdyk, Fabio Di Piazza, Sergio D. Bergese, MUMC+: Centrum voor Acute en Kritieke Zorg (3), Anesthesiologie, MUMC+: MA Anesthesiologie (9), and RS: MHeNs - R3 - Neuroscience
Subjects: medicine.medical_specialty, Asia, SURGERY, SHORT-ACTING OPIOIDS, Opioid, Continuous monitoring, EVENTS, Patient safety, Capnography, medicine, Humans, ANALGESICS, Adverse effect, Tramadol, General care floor, Depression (differential diagnoses), Pain, Postoperative, PAIN MANAGEMENT, medicine.diagnostic_test, business.industry, Incidence (epidemiology), COST, Apnea, HYPOXEMIA, RECOVERY, United States, Analgesics, Opioid, Anesthesiology and Pain Medicine, Anesthesia, Emergency medicine, Respiratory depression, Respiratory compromise, medicine.symptom, Respiratory Insufficiency, ACCESS, business, medicine.drug
Abstract: Study objective: Opioid administration for pain in general care floor patients remains common, and can lead to adverse outcomes, including respiratory compromise. The PRODIGY trial found that among ward patients receiving parenteral opioids, 46% experienced >= 1 respiratory depression episode. The objective of this analysis was to evaluate the geographic differences of opioid administration and examine the association between opioid administration characteristics and the occurrence of respiratory depression.Design: Prospective observational trial.Setting: 16 general care medical and surgical wards in Asia, Europe, and the United States.Patients: 1335 patients receiving parenteral opioids.Interventions: Blinded, alarm-silenced continuous capnography and pulse oximetry monitoring.Measurements: Opioid-induced respiratory depression, defined as respiratory rate = 60 mmHg for >= 3 min; apnea episode lasting >30 s; or any respiratory opioid-related adverse event.Results: Across all patients, 58% received only long-acting opioids, 16% received only short-acting (= 3 h) opioids. The type and median total morphine milligram equivalent (MME) of opioid administered varied significantly by region, with 31.5 (12.5-76.7) MME, 31.0 (6.2-99.0) MME, and 7.2 (1.7-18.7) MME in the United States, Europe, and Asia, respectively (p < 0.001). Considering only postoperative opioids, 54% (N = 119/220) and 45% (N = 347/779) of patients receiving only short-acting opioids or only long-acting opioids experienced >= 1 episode of opioid-induced respiratory depression, respectively. Multivariable analysis identified post-procedure tramadol (OR 0.62, 95% CI 0.424-0.905, p = 0.0133) and post-procedure epidural opioids (OR 0.485, 95% CI 0.322-0.731, p = 0.0005) being associated with a significant reduction in opioid-induced respiratory depression.Conclusions: Despite varying opioid administration characteristics between Asia, Europe, and the United States, opioid-induced respiratory depression remains a common global problem on general care medical and surgical wards. While the use of post-procedure tramadol or post-procedure epidural opioids may reduce the incidence of respiratory depression, continuous monitoring is also necessary to ensure patient safety when receiving post-operative opioids.
Published: 2021

46. Impact of Methylprednisolone on Postoperative Quality of Recovery and Delirium in the Steroids in Cardiac Surgery Trial

Author: Alistair Royse, Colin Royse, Ahmed Awais, Daniel I. Sessler, Jared Ou-Young, Philip J. Devereaux, Jessica Vincent, Krit Panjasawatwong, Leif Saager, Andrea Kurz, and Richard P. Whitlock
Subjects: medicine.medical_specialty, business.industry, 030204 cardiovascular system & hematology, Placebo, law.invention, Surgery, Cardiac surgery, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Methylprednisolone, Randomized controlled trial, 030202 anesthesiology, law, Anesthesia, Anesthesiology, medicine, Clinical endpoint, Cardiopulmonary bypass, Delirium, medicine.symptom, business, medicine.drug
Abstract: Background Inflammation after cardiopulmonary bypass may contribute to postoperative delirium and cognitive dysfunction. The authors evaluated the effect of high-dose methylprednisolone to suppress inflammation on the incidence of delirium and postoperative quality of recovery after cardiac surgery. Methods Five hundred fifty-five adults from three hospitals enrolled in the randomized, double-blind Steroids in Cardiac Surgery trial were randomly allocated to placebo or 250 mg methylprednisolone at induction and 250 mg methylprednisolone before cardiopulmonary bypass. Each completed the Postoperative Quality of Recovery Scale before surgery and on days 1, 2, and 3 and 1 and 6 months after surgery and the Confusion Assessment Method scale for delirium on days 1, 2, and 3. Recovery was defined as returning to preoperative values or improvement at each time point. Results Four hundred eighty-two participants for recovery and 498 participants for delirium were available for analysis. The quality of recovery improved over time but without differences between groups in the primary endpoint of overall recovery (odds ratio range over individual time points for methylprednisolone, 0.39 to 1.45; 95% CI, 0.08–2.04 to 0.40–5.27; P = 0.943) or individual recovery domains (all P > 0.05). The incidence of delirium was 10% (control) versus 8% (methylprednisolone; P = 0.357), with no differences in delirium subdomains (all P > 0.05). In participants with normal (51%) and low baseline cognition (49%), there were no significant differences favoring methylprednisolone in any domain (all P > 0.05). Recovery was worse in patients with postoperative delirium in the cognitive (P = 0.004) and physiologic (P < 0.001) domains. Conclusions High-dose intraoperative methylprednisolone neither reduces delirium nor improves the quality of recovery in high-risk cardiac surgical patients.
Published: 2017

47. Long-Acting Patient-Controlled Opioids Are Not Associated With More Postoperative Hypoxemia Than Short-Acting Patient-Controlled Opioids After Noncardiac Surgery

Author: Steve Leung, Leif Saager, Allan W. Belcher, P. J. Devereaux, Daniel I. Sessler, Matthew T Hutcherson, Ashish Khanna, Amanda J. Naylor, Natalya Makarova, and Bianka M Nguyen
Subjects: Male, Time Factors, Treatment outcome, Hypoxemia, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030202 anesthesiology, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Least-Squares Analysis, Hypoxia, Prospective cohort study, Aged, Pain, Postoperative, business.industry, Analgesia, Patient-Controlled, Middle Aged, Surgical procedures, Analgesics, Opioid, Oxygen, Treatment Outcome, Anesthesiology and Pain Medicine, Long acting, Oxyhemoglobins, Surgical Procedures, Operative, Postoperative hypoxemia, Anesthesia, Multivariate Analysis, Linear Models, Administration, Intravenous, Female, medicine.symptom, business, Noncardiac surgery, Biomarkers, Cohort study
Abstract: Opioids can contribute to postoperative desaturation. Short-acting opioids, titrated to need, may cause less desaturation than longer-acting opioids. We thus tested the primary hypothesis that long-acting patient-controlled intravenous opioids are associated with more hypoxemia (defined as an integrated area under a postoperative oxyhemoglobin saturation of 95%) than short-acting opioids.This analysis was a substudy of VISION, a prospective cohort study focused on perioperative cardiovascular events (NCT00512109). After excluding for predefined criteria, 191 patients were included in our final analysis, with 75 (39%) patients being given fentanyl (short-acting opioid group) and 116 (61%) patients being given morphine and/or hydromorphone (long-acting opioid group). The difference in the median areas under a postoperative oxyhemoglobin saturation of 95% between short-acting and long-acting opioids was compared using multivariable median quantile regression.The short-acting opioid median area under a postoperative oxyhemoglobin saturation of 95% per hour was 1.08 (q1, q3: 0.62, 2.26) %-h, whereas the long-acting opioid median was 1.28 (0.50, 2.23) %-h. No significant association was detected between long-acting and short-acting opioids and median area under a postoperative oxyhemoglobin saturation of 95% per hour (P = .66) with estimated change in the medians of -0.14 (95% CI, -0.75, 0.47) %-h for the patients given long-acting versus short-acting IV patient-controlled analgesia opioids.Long-acting patient-controlled opioids were not associated with the increased hypoxemia during the first 2 postoperative days.
Published: 2016

48. A randomized trial of prewarming on patient satisfaction and thermal comfort in outpatient surgery

Author: Alexa N. Fiffick, Zohaib Akhtar, Sabry Ayad, Brian D. Hesler, Andrea Kurz, Daniel I. Sessler, Leif Saager, and Edward J. Mascha
Subjects: Adult, Male, Adolescent, Visual analogue scale, Outpatient surgery, Body Temperature, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Patient satisfaction, Randomized controlled trial, Hypothermia, Induced, 030202 anesthesiology, law, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Patient Comfort, Rewarming, Aged, Intraoperative Care, business.industry, Thermal comfort, Perioperative, Middle Aged, Hypothermia, Confidence interval, Treatment Outcome, Anesthesiology and Pain Medicine, Ambulatory Surgical Procedures, Patient Satisfaction, Anesthesia, Female, medicine.symptom, business
Abstract: Study objective To test the primary hypothesis that forced-air prewarming improves patient satisfaction after outpatient surgery and to evaluate the effect on core temperature and thermal comfort. Design Prospective randomized controlled trial. Setting Preoperative area, operating room, and postanesthesia care unit. Patients A total of 115 patients aged 18 to 75 years with American Society of Anesthesiologists status 2 who were undergoing outpatient surgery (duration Interventions Patients were randomized to active prewarming with a Mistral-Air warming system initially set to 43°C or no active prewarming. All patients were warmed intraoperatively. Measurements Demographic and morphometric characteristics, perioperative core temperature, ambient temperature, EVAN-G satisfaction score, thermal comfort via visual analog scales. Main Results Data from 102 patients were included in the final analysis. Prewarming did not significantly reduce redistribution hypothermia, with prewarmed minus not prewarmed core temperature differing by only 0.18°C (95% confidence interval [CI], −0.001 to 0.37) during the initial hour of anesthesia ( P =.052). Prewarming increased the mean EVAN-G satisfaction score, although not significantly, with an overall difference (prewarmed minus not prewarmed) of 5.6 (95% CI, −0.9 to 12.2; P =.09). Prewarming increased thermal comfort, with an overall difference of 6.6 mm (95% CI, 1.0-12.9; P =.02). Conclusion Active prewarming increased thermal comfort but did not significantly reduce redistribution hypothermia or improve postoperative patient satisfaction.
Published: 2016

49. Subcutaneous perfusion before and during surgery in obese and nonobese patients

Author: Heiko Kaiser, Dagmar J. Kaiser, Vladimir Krejci, Gabor Erdoes, Leif Saager, and Luzius B. Hiltebrand
Subjects: medicine.medical_specialty, business.industry, Case-control study, Surgical wound, Dermatology, Hypoxia (medical), Surgery, Oxygen tension, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030202 anesthesiology, Anesthesia, medicine, medicine.symptom, business, Surgical incision, Perfusion, Abdominal surgery, Subcutaneous tissue
Abstract: Hypoxia at the surgical site impairs wound healing and oxidative killing of microbes. Surgical site infections are more common in obese patients. We hypothesized that subcutaneous oxygen tension (Psq O2) would decrease substantially in both obese and non-obese patients following induction of anesthesia and after surgical incision. We performed a prospective observational study that enrolled obese and non-obese surgical patients and measured serial Psq O2 before and during surgery. Seven morbidly obese and seven non-obese patients were enrolled. At baseline breathing room air, Psq O2 values were not significantly different (p = 0.66) between obese (6.8 kPa) and non-obese (6.5 kPa) patients. The targeted arterial oxygen tension (40 kPa) was successfully achieved in both groups with an expected significant increase in Psq O2 (obese 16.1 kPa and non-obese 13.4 kPa; p = 0.001). After induction of anesthesia and endotracheal intubation, Psq O2 did not change significantly in either cohort in comparison to levels right before induction (obese 15.5, non-obese 13.5 kPa; p = 0.95), but decreased significantly during surgery (obese 10.1, non-obese 9.3 kPa; p = 0.01). In both morbidly obese and non-obese patients, Psq O2 does not decrease appreciably following induction of anesthesia, but decreases markedly (∼33%) after commencement of surgery. Given the theoretical risks associated with low Psq O2 , future research should investigate how Psq O2 can be maintained after surgical incision.
Published: 2015

50. Incidence of insufficient intraoperative neuromuscular paralysis. A retrospective registry analysis

Author: Daniel I. Sessler, Cameron Egan, Andrea Kurz, Brian D. Hesler, Edward J. Mascha, Scott Devine, Alparslan Turan, Leif Saager, and Dongsheng Yang
Subjects: Adult, Male, Delphi Technique, Muscle Relaxation, Endotracheal intubation, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, medicine, Paralysis, Humans, 030212 general & internal medicine, Registries, Intraoperative Complications, Aged, Retrospective Studies, Dose-Response Relationship, Drug, business.industry, Incidence (epidemiology), Incidence, Retrospective cohort study, Middle Aged, Neurovascular bundle, Neuromuscular monitoring, Anesthesiology and Pain Medicine, Muscle relaxation, Anesthesia, Surgical Procedures, Operative, Anesthetic, Neuromuscular Blockade, Female, Neuromuscular Monitoring, medicine.symptom, business, medicine.drug, Neuromuscular Nondepolarizing Agents
Abstract: Study objective Muscular tone that inhibits anesthetic or surgical care characterizes insufficient neuromuscular block. The incidence of insufficient neuromuscular block is unknown, therefore we developed novel electronic search strategies to identify occurrences of insufficient neuromuscular block. Our primary goal was to determine the incidence of intraoperative insufficient neuromuscular block in abdominal and neurovascular surgery. Our secondary goal was to assess factors independently associated with insufficient block. Design Retrospective cohort. Setting Operating rooms in a tertiary care center. Patients Adults having abdominal, laparoscopic, and interventional neurovascular procedures under general anesthesia with endotracheal intubation between April 2005 and February 2013. Measurements An expert panel of anesthesiologists used a Delphi process to develop criteria to identify insufficient intraoperative neuromuscular block. 10 final criteria were agreed upon and used to determine the incidence of insufficient neuromuscular block. Main results 48,315 surgeries met our inclusion requirements. Intraoperative insufficient neuromuscular block was identified in 13,538 cases, representing 28% (95% CI: 27.6%, 28.4%) of the operations. Younger age, male sex, type of surgery, longer duration of surgery, pre-existing conditions, and use of volatile anesthetics were independently associated with insufficient block after Bonferroni correction. Conclusion Our results suggest that episodes of insufficient block occur in over a quarter of operations that are generally thought to require muscle relaxation. Without neuromuscular monitoring, it is difficult to separate inadequate anesthesia from inadequate neuromuscular block, and both presumably contributed in many cases.
Published: 2018

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