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1. The association between intraoperative low driving pressure ventilation and perioperative healthcare-associated costs: A retrospective multicenter cohort study

Author

Wachtendorf, Luca J., Ahrens, Elena, Suleiman, Aiman, von Wedel, Dario, Tartler, Tim M., Rudolph, Maíra I., Redaelli, Simone, Santer, Peter, Munoz-Acuna, Ricardo, Santarisi, Abeer, Calderon, Harold N., Kiyatkin, Michael E., Novack, Lena, Talmor, Daniel, Eikermann, Matthias, and Schaefer, Maximilian S.

Published
2024
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5. Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit.

Author

Azimaraghi, Omid, Hammer, Maximilian, Santer, Peter, Platzbecker, Katharina, Althoff, Friederike C, Patrocinio, Maria, Grabitz, Stephanie D, Wongtangman, Karuna, Rumyantsev, Sandra, Xu, Xinling, Schaefer, Maximilian S, Fuller, Patrick M, Subramaniam, Balachundhar, and Eikermann, Matthias

Subjects
Humans, Delirium, Azepines, Triazoles, Stroke Volume, Treatment Outcome, Double-Blind Method, Sleep, Pregnancy, Ventricular Function, Left, Adult, Middle Aged, Intensive Care Units, Female, Randomized Controlled Trials as Topic, Orexin Receptor Antagonists, anaesthetics, cardiac surgery, clinical trials, delirium & cognitive disorders, sleep medicine, Sleep Research, Neurosciences, Aging, Clinical Trials and Supportive Activities, Mental Health, Patient Safety, Clinical Research, Behavioral and Social Science, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

IntroductionInsomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients.Methods and analysisIn this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 120 patients, aged 60 years or older, undergoing elective cardiac surgery with planned postoperative admission to the ICU. Participants will be randomised to receive oral suvorexant (20 mg) or placebo one time a day starting the night after extubation. The primary outcome will be wakefulness after persistent sleep onset. The secondary outcome will be total sleep time. Exploratory outcomes will include time to sleep onset, incidence of postoperative in-hospital delirium, number of delirium-free days and subjective sleep quality.Ethics and disseminationEthics approval was obtained through the 'Committee on Clinical Investigations' at Beth Israel Deaconess Medical Center (protocol number 2019P000759). The findings will be published in peer-reviewed journals.Trial registration numberThis trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).

Published
2020

10. Iron, hypoxia and chronic disease

Author

Santer, Peter and Robbins, Peter

Subjects
612.2, Respiration, Human physiology
Abstract

The main theme of this thesis is centred around the physiology and pathophysiology of two elements essential for human life: oxygen and iron. The work presented here is focused on the complex regulatory mechanisms, the interactions between iron and oxygen and the perturbations within those pathways underlying various disease conditions. Translational applications are presented in the settings of chronic obstructive pulmonary disease (COPD), critical illness and hypoxic conditioning. In Chapter 3, a randomised, controlled clinical trial investigating the effects of iron augmentation in patients with COPD is presented. In this study, 48 participants received a single dose of either intravenous iron (ferric carboxymaltose) or placebo. Over an eight-week period, oxygenation, exercise performance, symptomatology, health-related quality of life and lung function were assessed. Intravenous iron did not improve peripheral oxygen saturation. However, participants receiving an iron infusion walked farther and were less breathless. Six-minute walk distance improved by 14 ± 8 m after eight weeks following iron administration compared to placebo (p = 0.025). Improvements ≥ 40 m were observed in 29.2% of iron-treated and 0% of placebo-treated participants after one week (p = 0.009). MRC dyspnoea scores were lower one week after iron treatment, with a larger fraction of participants reporting scores ≤ 1 in the iron group than in the placebo group (66.7% vs. 33.3%, p = 0.021). Adverse event rates were similar in both groups except for hypophosphataemia, a common and well-known side effect of ferric carboxymaltose, which occurred more frequently in the iron group (91.7% vs. 8.3%, p = 0.001). This decrease in serum phosphate levels remained asymptomatic. Chapter 4 presents results from the retrospective analysis of iron status in critically ill patients. Inflammation commonly occurs in these patients as highlighted by elevated inflammatory markers C-reactive protein and interleukin-6. Several iron parameters, including serum iron, ferritin, hepcidin, transferrin, and transferrin saturation, strongly correlated with the increase in inflammatory markers. Anaemia, often a consequence of iron sequestration in systemic inflammation, was observed in nearly all patients. Chapter 5 describes a small study investigating the effects of prolonged exposure to hypoxia in healthy 50-70-year-old volunteers. Using a residential hypoxia facility, eight participants were exposed to mild hypoxia for one week in a crossover study design. The exposure to 15% of inspired oxygen fraction resulted in physiological adaptations, including increased heart rate, respiratory rate, haemoglobin, and haematocrit. Erythropoietin, a marker of hypoxia signalling, and hepcidin, the main regulator of iron homeostasis, were assessed by enzyme-linked immunosorbent assay. While erythropoietin was significantly elevated in response to hypoxia, hepcidin levels decreased. The exposure to hypoxia was well-tolerated by all participants. A main summary, overall conclusions, and an outlook are provided in Chapter 6.

Published
2018

20. Adjustments of Ventilator Parameters during Operating Room–to–ICU Transition and 28-Day Mortality

Author

von Wedel, Dario, primary, Redaelli, Simone, additional, Suleiman, Aiman, additional, Wachtendorf, Luca J., additional, Fosset, Maxime, additional, Santer, Peter, additional, Shay, Denys, additional, Munoz-Acuna, Ricardo, additional, Chen, Guanqing, additional, Talmor, Daniel, additional, Jung, Boris, additional, Baedorf-Kassis, Elias N., additional, and Schaefer, Maximilian S., additional

Published
2024
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21. Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial

Author

Santer, Peter, Anstey, Matthew H., Patrocínio, Maria D., Wibrow, Bradley, Teja, Bijan, Shay, Denys, and Shaefi, Shahzad

Subjects
Clinical trials, Hospital patients, Health care industry
Abstract

Purpose ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral [alpha].sub.1-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement. Methods In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for [greater than or equal to] 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates. Results Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02). Conclusion Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients., Author(s): Peter Santer [sup.1], Matthew H. Anstey [sup.2] [sup.3], Maria D. Patrocínio [sup.1], Bradley Wibrow [sup.2] [sup.3], Bijan Teja [sup.4], Denys Shay [sup.1], Shahzad Shaefi [sup.1], Charles S. Parsons [sup.5], [...]

Published
2020
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24. Neutrophil-Derived Protein S100A8/A9 Alters the Platelet Proteome in Acute Myocardial Infarction and Is Associated With Changes in Platelet Reactivity

Author

Joshi, Abhishek, Schmidt, Lukas E., Burnap, Sean A., Lu, Ruifang, Chan, Melissa V., Armstrong, Paul C., Baig, Ferheen, Gutmann, Clemens, Willeit, Peter, Santer, Peter, Barwari, Temo, Theofilatos, Konstantinos, Kiechl, Stefan, Willeit, Johann, Warner, Timothy D., Mathur, Anthony, and Mayr, Manuel

Published
2022
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35. Tetrahydrobiopterin compounds modulate intracellular signaling and reactive oxygen species levels in an in vitro model of ischemia-reperfusion injury

Author

Santer Peter, Ratschiller Thomas, Ashraf Muhammad Imtiaz, Werner Ernst R., Werner-Felmayer Gabriele, Maglione Manuel, Brandacher Gerald, and Troppmair Jakob

Subjects
4-amino-tetrahydrobiopterin (abh4), ischemia-reperfusion injury, mitogen-activated protein kinase (mapk) signaling, reactive oxygen species (ros), tetrahydrobiopterin (bh4), Crystallography, QD901-999
Abstract

Tetrahydrobiopterin (BH4) and 4-amino-tetrahydrobiopterin (ABH4) prevent acute rejection after solid organ transplantation. Moreover, BH4 also attenuates ischemia-reperfusion injury (IRI). The mechanisms underlying these protective effects are poorly defined. Activation of intracellular signaling proteins, including the mitogen-activated protein kinases (MAPKs) ERK, p38, and JNK, and the excessive production of mitochondrial reactive oxygen species (ROS) are observed mainly during early reperfusion. While the role of ROS in the initiation and progression of IRI is well understood, the contribution of individual signaling pathways is less clear. Here, we tested the potential effects of BH4 and ABH4 on MAPK activity and mitochondrial ROS levels. During hypoxia and reoxygenation (H/R), all three MAPKs were activated during early reoxygenation in cardiomyocytes and endothelial cells. p38 and JNK activation were further augmented by BH4 and ABH4, whereas ERK activation was not affected. Pretreatment with BH4 and ABH4 reduced the basal mitochondrial ROS levels as well as the H/R-induced increase in ROS. Prolonged incubation with ABH4, however, showed pro-apoptotic effects in cardiomyocytes. These data suggest that a protective effect of BH4 and ABH4 pretreatment may be attributed mainly to their antioxidant capacity. The effects on intracellular signaling are complex and warrant further investigations.

Published
2013
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36. Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients

Author

Suleiman, Aiman, primary, Santer, Peter, additional, Munoz-Acuna, Ronny, additional, Hammer, Maximilian, additional, Schaefer, Maximilian S., additional, Wachtendorf, Luca J., additional, Rumyantsev, Sandra, additional, Berra, Lorenzo, additional, Chamadia, Shubham, additional, Johnson-Akeju, Oluwaseun, additional, Baedorf-Kassis, Elias N., additional, and Eikermann, Matthias, additional

Published
2022
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39. sj-docx-1-jic-10.1177_08850666221119716 - Supplemental material for Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients

Author

Suleiman, Aiman, Santer, Peter, Munoz-Acuna, Ronny, Hammer, Maximilian, Schaefer, Maximilian S., Wachtendorf, Luca J., Rumyantsev, Sandra, Berra, Lorenzo, Chamadia, Shubham, Johnson-Akeju, Oluwaseun, Baedorf-Kassis, Elias N., and Eikermann, Matthias

Subjects
110203 Respiratory Diseases, FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110305 Emergency Medicine
Abstract

Supplemental material, sj-docx-1-jic-10.1177_08850666221119716 for Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients by Aiman Suleiman, Peter Santer, Ronny Munoz-Acuna, Maximilian Hammer, Maximilian S. Schaefer and Luca J. Wachtendorf, Sandra Rumyantsev, Lorenzo Berra, Shubham Chamadia, Oluwaseun Johnson-Akeju, Elias N. Baedorf-Kassis, Matthias Eikermann in Journal of Intensive Care Medicine

Published
2022
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40. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses

Author

Drechsler, Christiane, Bolland, Mark J., Reid, Ian, Willeit, Johann, Schett, Georg, Santer, Peter, Sofat, Reecha, Taylor, Julie, Dale, Caroline, Prince, Richard L., Ben-Shlomo, Yoav, Gallacher, John, Jensen, Gorm B., Frikke-Schmidt, Ruth, Bojesen, Stig Egil, Benn, Marianne, Wulff, Anders B., Krogh, Signe V., Schierbeck, Louise Lind, Kaptoge, Stephen, Wareham, Nicholas, Schöttker, Ben, Zhu, Anna, Holleczek, Bernd, Dennison, Elaine, Jameson, Karen, Schleithoff, Stefanie Schulze, Frisch, Sabine, Linneberg, Allan, Skaaby, Tea, Kårhus, Line Lund, de Jongh, Renate T., Visser, Marjolein, Dobnig, Harald, Robinson-Cohen, Cassianne, Siscovick, David S., Kestenbaum, Bryan R., McConnachie, Alex, Sattar, Naveed, Morrison, David, Lundqvist, Annamari, Cawthon, Peggy M., Albertorio, Juan R., Jukema, J Wouter, Trompet, Stella, Kearney, Patricia, Dörr, Marcus, Völzke, Henry, Nauck, Matthias, Rossing, Peter, Persson, Frederik, Marniemi, Jukka, Vazquez, Victoria, Sundström, Johan, Risérus, Ulf, Michaëlsson, Karl, Emberson, Jonathan, Leon, David, and Kivimäki, Mika

Abstract

Background:\ud Randomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.\ud \ud Methods:\ud Observational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality.\ud \ud Findings:\ud Observational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration

Published
2021

41. Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients.

Author

Suleiman, Aiman, Santer, Peter, Munoz-Acuna, Ronny, Hammer, Maximilian, Schaefer, Maximilian S., Wachtendorf, Luca J., Rumyantsev, Sandra, Berra, Lorenzo, Chamadia, Shubham, Johnson-Akeju, Oluwaseun, Baedorf-Kassis, Elias N., and Eikermann, Matthias

Subjects
*KETAMINE, *RESPIRATION, *PROPOFOL, *INTENSIVE care patients, *ULTRASONIC encephalography, *ANESTHESIA
Abstract

Background: Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. Methods: In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 h each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced change in beta-gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. Results: Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively (p =.013). Resistive work of breathing decreased from 0.4 (0.1-0.6) J/l at baseline to 0.2 (0.1-0.3) J/l after ketamine 10 mcg/kg/min (p =.042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline (p <.01). Conclusions: In intubated, spontaneously breathing patients receiving a constant rate of propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an "activated" electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation. [ABSTRACT FROM AUTHOR]

Published
2023
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43. Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study From a New England Health Care Network

Author

Azimaraghi, Omid, primary, Wongtangman, Karuna, additional, Wachtendorf, Luca J., additional, Santer, Peter, additional, Rumyantsev, Sandra, additional, Ahn, Curie, additional, Kiyatkin, Michael E., additional, Teja, Bijan, additional, Sarge, Todd, additional, Subramaniam, Balachundhar, additional, and Eikermann, Matthias, additional

Published
2022
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47. Signature of circulating microRNAs in osteoarthritis

Author

Beyer, Christian, Zampetaki, Anna, Lin, Neng-Yu, Kleyer, Arnd, Perricone, Carlo, Iagnocco, Annamaria, Distler, Alfiya, Langley, Sarah R, Gelse, Kolja, Sesselmann, Stefan, Lorenzini, Rolando, Niemeier, Andreas, Swoboda, Bernd, Distler, Jörg HW, Santer, Peter, Egger, Georg, Willeit, Johann, Mayr, Manuel, Schett, Georg, and Kiechl, Stefan

Published
2015
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48. Both SARS-CoV-2 infection and vaccination in pregnancy elicited neutralizing antibodies in pregnant women and newborns

Author

Cassaniti, Irene, primary, Percivalle, Elena, additional, Zelini, Paola, additional, Ngaradoumbe Nanhorngue, Kimta, additional, Parolo, Anna, additional, Bernardi, Valeria, additional, Jorizzo, Gianfranco, additional, Santer, Peter, additional, Perotti, Francesca, additional, Spinillo, Arsenio, additional, Lilleri, Daniele, additional, and Baldanti, Fausto, additional

Published
2021
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49. Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study

Author

Wachtendorf, Luca J., primary, Azimaraghi, Omid, additional, Santer, Peter, additional, Linhardt, Felix C., additional, Blank, Michael, additional, Suleiman, Aiman, additional, Ahn, Curie, additional, Low, Ying H., additional, Teja, Bijan, additional, Kendale, Samir M., additional, Schaefer, Maximilian S., additional, Houle, Timothy T., additional, Pollard, Richard J., additional, Subramaniam, Balachundhar, additional, Eikermann, Matthias, additional, and Wongtangman, Karuna, additional

Published
2021
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