Willem‐Jan M. Schellekens

Utrecht University

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Leo Heunks

Radboud University Nijmegen

Johannes G. van der Hoeven

Radboud University Nijmegen

Hieronymus W. H. van Hees

Radboud University Medical Center

Marianne Linkels

Radboud University Nijmegen

Gert Jan Scheffer

Radboud University Nijmegen

Nikki de Mul

University Medical Center Utrecht

Hieronymus WH van Hees

Radboud University Medical Center

Matthijs Kox

Radboud University Medical Center

PN Richard Dekhuijzen

Radboud University Nijmegen

Jonne Doorduin

Radboud University Medical Center

Cooperative Institutions

University Medical Center Utrecht

Utrecht University

Radboud University Nijmegen

Radboud University Medical Center

University Medical Center

University Hospital Heidelberg

Heidelberg University

Amsterdam University Medical Centers

Radboud Institute for Molecular Life Sciences

University of Amsterdam

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Hypoxemia during procedural sedation in adult patients: a retrospective observational study

Canadian Journal of Anesthesia/Journal canadien d anesthésie (2021)

Eva P. C. van Schaik Paul Blankman Wilton A. van Klei H Knape Paul H. H. B. Vaessen

Since 2010, new guidelines for procedural sedation and the Helsinki Declaration on Patient Safety have increased patient safety, comfort, and acceptance considerably. Nevertheless, the administration of sedatives and opioids during sedation procedures may put the patient at risk of hypoxemia. However, data on hypoxemia during procedural sedation are scarce. Here, we studied the incidence and severity of hypoxemia during procedural sedations in our hospital. A historical, single-centre cohort study was performed at the University Medical Centre Utrecht (UMCU), a tertiary centre in the Netherlands. Data from procedural sedation in our hospital between 1 January 2011 and 31 December 2018 (3,459 males and 2,534 females; total, 5,993) were extracted from our Anesthesia Information Management System. Hypoxemia was defined as peripheral oxygen saturation < 90% lasting at least two consecutive minutes. The severity of hypoxemia was calculated as area under the curve. The relationship between the severity of hypoxemia and body mass index (BMI), American Society of Anesthesiologists (ASA) Physical Status classification, and duration of the procedure was investigated. The primary outcome was the incidence of hypoxemia. Twenty-nine percent of moderately to deeply sedated patients developed hypoxemia. A high incidence of hypoxemia was found in patients undergoing procedures in the heart catheterization room (54%) and in patients undergoing bronchoscopy procedures (56%). Hypoxemia primarily occurred in longer lasting procedures (> 120 min) and especially in the latter phases of the procedures. There was no relationship between severity of hypoxemia and BMI or ASA Physical Status. This study showed that a considerable number of patients are at risk of hypoxemia during procedural sedation with a positive correlation shown with increasing duration of medical procedures. Additional prospective research is needed to investigate the clinical consequences of this cumulative hypoxemia.

10.1007/s12630-021-01992-6

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Citations (25)

Respiratory Muscles and Ventilator-induced Lung Injury Critical Care

American Journal of Respiratory and Critical Care Medicine (2017)

Willem‐Jan M. Schellekens Diana Jansen Mirrin J. Dorresteijn Leo Heunks

Respiratory care

10.1164/rccm.201608-1627rr

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Delirium and long-term psychopathology following surgery in older adults

Journal of Psychosomatic Research (2022)

Nikki de Mul Lisa M.E.C. van den Bos Ilse Kant Simone J.T. van Montfort Willem‐Jan M. Schellekens

To describe the risk of postoperative delirium and long-term psychopathology (depression, anxiety or post-traumatic stress syndrome (PTSS)) in older adults.255 elderly patients (≥ 65 years) undergoing major surgery (planned surgical time > 60 min) in a tertiary hospital were compared to 76 non-surgical controls from general practice. Patients were assessed twice daily for postoperative delirium using the Confusion Assessment Method (CAM(-ICU)), nursing delirium screening scale (NuDESC) and validated chart review. Before surgery and 3 and 12 months thereafter, the participants filled in the Hospital Anxiety and Depression Scale (HADS), the Geriatric Depression Scale (GDS-15) and the Post-Traumatic Stress Syndrome-14-Questions Inventory (PTSS-14). Non-surgical controls filled in the same questionnaires with similar follow-up.Patients were more often male, had higher American Society of Anesthesiologists scores and more often had a spouse compared to controls (p < 0.005). Forty-three patients (18%) developed postoperative delirium, who were significantly older, had higher ASA scores and lower estimated IQ scores compared to the patients who did not develop delirium (p < 0.05). There were no differences in psychopathology at baseline and 3-month follow-up between patients and controls. At 12-months, surgical patients less frequently scored positive for depression (7% versus 16%) and anxiety (2% versus 10%) compared to nonsurgical controls (p < 0.05). We did not observe differences in occurrence of psychopathology between patients who had and had not developed postoperative delirium.Our results suggest that the older surgical population, with or without postoperative delirium, does not appear to be at greater risk of developing psychopathology. WHY DOES THIS PAPER MATTER?: The older surgical population does not appear to be at greater risk of developing psychopathology, neither seems this risk influenced by the occurrence of postoperative delirium.

Depression

Organic mental disorders

Geriatric Depression Scale

10.1016/j.jpsychores.2022.110746

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Citations (2)

Strategies to optimize respiratory muscle function in ICU patients

Critical Care (2016)

Willem‐Jan M. Schellekens Hieronymus W. H. van Hees Jonne Doorduin Lisanne H. Roesthuis Gert Jan Scheffer

Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality. This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved. We propose a simple strategy for how these can be implemented in clinical care.

Muscle weakness

Respiratory care

10.1186/s13054-016-1280-y

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Citations (54)

Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice

Critical Care (2015)

Willem‐Jan M. Schellekens Hieronymus WH van Hees Marianne Linkels PN Richard Dekhuijzen Gert Jan Scheffer

Controlled mechanical ventilation and endotoxemia are associated with diaphragm muscle atrophy and dysfunction. Oxidative stress and activation of inflammatory pathways are involved in the pathogenesis of diaphragmatic dysfunction. Levosimendan, a cardiac inotrope, has been reported to possess anti-oxidative and anti-inflammatory properties. The aim of the present study was to investigate the effects of levosimendan on markers for diaphragm nitrosative and oxidative stress, inflammation and proteolysis in a mouse model of endotoxemia and mechanical ventilation.Three groups were studied: (1) unventilated mice (CON, n =8), (2) mechanically ventilated endotoxemic mice (MV LPS, n =17) and (3) mechanically ventilated endotoxemic mice treated with levosimendan (MV LPS + L, n =17). Immediately after anesthesia (CON) or after 8 hours of mechanical ventilation, blood and diaphragm muscle were harvested for biochemical analysis.Mechanical ventilation and endotoxemia increased expression of inducible nitric oxide synthase (iNOS) mRNA and cytokine levels of interleukin (IL)-1β, IL-6 and keratinocyte-derived chemokine, and decreased IL-10, in the diaphragm; however, they had no effect on protein nitrosylation and 4-hydroxy-2-nonenal protein concentrations. Levosimendan decreased nitrosylated proteins by 10% (P <0.05) and 4-hydroxy-2-nonenal protein concentrations by 13% (P <0.05), but it augmented the rise of iNOS mRNA by 47% (P <0.05). Levosimendan did not affect the inflammatory response in the diaphragm induced by mechanical ventilation and endotoxemia.Mechanical ventilation in combination with endotoxemia results in systemic and diaphragmatic inflammation. Levosimendan partly decreased markers of nitrosative and oxidative stress, but did not affect the inflammatory response.

Levosimendan

Diaphragm (acoustics)

10.1186/s13054-015-0798-8

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Citations (20)

Mechanical ventilation of mice under general anesthesia during experimental procedures

Lab Animal (2013)

I. van den Brink F. van de Pol Michiel Vaneker Matthijs Kox Willem‐Jan M. Schellekens

10.1038/laban.252

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Citations (1)

Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction

Critical Care (2014)

Willem‐Jan M. Schellekens Hieronymus WH van Hees Matthijs Kox Marianne Linkels Gilberto L. Andrade Acuňa

Diaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator. Hypercapnia is an accepted side effect of low tidal volume mechanical ventilation, but the effects of hypercapnia on respiratory muscle function are largely unknown. The present study investigated the effect of hypercapnia on ventilator-induced diaphragm inflammation, atrophy and function.Male Wistar rats (n = 10 per group) were unventilated (CON), mechanically ventilated for 18 hours without (MV) or with hypercapnia (MV + H, Fico2 = 0.05). Diaphragm muscle was excised for structural, biochemical and functional analyses.Myosin concentration in the diaphragm was decreased in MV versus CON, but not in MV + H versus CON. MV reduced diaphragm force by approximately 22% compared with CON. The force-generating capacity of diaphragm fibers from MV + H rats was approximately 14% lower compared with CON. Inflammatory cytokines were elevated in the diaphragm of MV rats, but not in the MV + H group. Diaphragm proteasome activity did not significantly differ between MV and CON. However, proteasome activity in the diaphragm of MV + H was significantly lower compared with CON. LC3B-II a marker of lysosomal autophagy was increased in both MV and MV + H. Incubation of MV + H diaphragm muscle fibers with the antioxidant dithiothreitol restored force generation of diaphragm fibers.Hypercapnia partly protects the diaphragm against adverse effects of mechanical ventilation.

Diaphragm (acoustics)

10.1186/cc13719

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Citations (23)

Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy

Anesthesiology (2012)

Willem‐Jan M. Schellekens Hieronymus W. H. van Hees Michiel Vaneker Marianne Linkels P. N. Richard Dekhuijzen

Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy.Unventilated animals were selected for control: wild-type (n = 6) and Toll-like receptor 4 deficient mice (n = 6). Mechanical ventilation (8 h): wild-type (n = 8) and Toll-like receptor 4 deficient (n = 7) mice.Myosin heavy chain content, proinflammatory cytokines, proteolytic activity of the ubiquitin-proteasome pathway, caspase-3 activity, and autophagy were measured in the diaphragm.Mechanical ventilation reduced myosin content by approximately 50% in diaphragms of wild-type mice (P less than 0.05). In contrast, ventilation of Toll-like receptor 4 deficient mice did not significantly affect diaphragm myosin content. Likewise, mechanical ventilation significantly increased interleukin-6 and keratinocyte-derived chemokine in the diaphragm of wild-type mice, but not in ventilated Toll-like receptor 4 deficient mice. Mechanical ventilation increased diaphragmatic muscle atrophy factor box transcription in both wild-type and Toll-like receptor 4 deficient mice. Other components of the ubiquitin-proteasome pathway and caspase-3 activity were not affected by ventilation of either wild-type mice or Toll-like receptor 4 deficient mice. Mechanical ventilation induced autophagy in diaphragms of ventilated wild-type mice, but not Toll-like receptor 4 deficient mice.Toll-like receptor 4 signaling plays an important role in the development of ventilator-induced diaphragm atrophy, most likely through increased expression of cytokines and activation of lysosomal autophagy.

Proinflammatory cytokine

10.1097/aln.0b013e3182608cc0

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Citations (45)

Appropriate positioning of the NAVA catheter

Intensive Care Medicine (2016)

Willem‐Jan M. Schellekens Leo Heunks

Pain medicine

10.1007/s00134-016-4213-y

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Citations (3)

Letter to the Editor

The Journal of Physiology (2015)

Willem‐Jan M. Schellekens Hieronymus W. H. van Hees Leo Heunks

With great interest we read the paper by Corpeno and colleagues that reports the time course of mechanical ventilation-induced diaphragm contractile muscle dysfunction in the rat (Corpeno et al. 2014). In their study, rats were mechanically ventilated for up to 14 days and a time-resolved analysis of the diaphragm structure and function was performed. In the first 4 days of controlled mechanical ventilation, specific force generation of muscle fibres was significantly decreased in the presence of protein modifications associated with oxidative stress. Surpri-singly, cross sectional area (CSA) of these muscle fibres was not affected in the first 4 days of mechanical ventilation. This led the authors to conclude that a reduction of muscle fibre size is not a dominating factor underlying the early decline in diaphragm muscle function in response to controlled mechanical ventilation. In our opinion, two important issues potentially confound their findings on diaphragm muscle fibre size. Firstly, rapid induced atrophy of the diaphragm due to controlled mechanical ventilation has consistently been established in animals (Shanely et al. 2002; Maes et al. 2007; Schellekens et al. 2014). In all these studies, diaphragm atrophy was assessed by CSA measurement of the specific fibre types (fast and slow), whereas this was not done in the paper by Corpeno et al. (Fig.1). Since CSA differs significantly among fibre types (Eddinger & Moss, 1987; Shanely et al. 2002; Maes et al. 2007), this may have underestimated the degree of diaphragm atrophy in their study. Accordingly, to establish the presence of diaphragm atrophy muscle fibre size should be reported per fibre type. Secondly, for unexplained reasons the authors applied high inspiratory fractions of CO2 () in their experimental setup. This may have had important unnoticed effects on diaphragm fibre size. Recently, we demonstrated that hypercapnia protected against the development of diaphragm atrophy during 18 h of mechanical ventilation in rats (Schellekens et al. 2014). In that study we induced hypercapnia by applying an of 0.05. Corpeno et al. 2014report an of 0.03 in their mechanical ventilation model. It is therefore likely that their animals developed hypercapnia, which consequently attenuated ventilator-induced diaphragm atrophy. It must be emphasized that Corpeno and colleagues have conducted a challenging and important study that adds to our understanding of the pathophysiology of ventilator-induced diaphragm dysfunction. However, the authors need to be more careful in their conclusion that diaphragm fibre atrophy does not develop early in ventilated rats, as this cannot be concluded with certainty from their results. Understanding the mechanisms resulting in diaphragm dysfunction in ventilated animals and ultimately critically ill patients is of major importance in order to develop effective strategies to combat the development of respiratory muscle dysfunction in these patients. Insight in early and late responses is important and may affect treatment strategies.

Diaphragm (acoustics)

Muscle Atrophy

Diaphragm muscle

Muscle fibre

10.1113/jp270385

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