581 research outputs found
sj-docx-1-bmi-10.1177_11772719221099131 – Supplemental material for Identification of Potential Urinary Metabolite Biomarkers of <i>Pseudomonas aeruginosa</i> Ventilator-Associated Pneumonia
No full textSupplemental material, sj-docx-1-bmi-10.1177_11772719221099131 for Identification of Potential Urinary Metabolite Biomarkers of Pseudomonas aeruginosa Ventilator-Associated Pneumonia by Bart’s Jongers, An Hotterbeekx, Kenny Bielen, Philippe Vervliet, Jan Boddaert, Christine Lammens, Erik Fransen, Geert Baggerman, Adrian Covaci, Herman Goossens, Surbhi Malhotra-Kumar, Philippe G Jorens and Samir Kumar-Singh in Biomarker Insights</p
Visualising respiratory dysfunction during and after mechanical ventilation : a translational approach using imaging, electromyograpy and biomarkers
No full textEffects of the clinical application of citrate anticoagulation for continuous renal replacement therapy and cell salvage
No full textAbstract: After an introductory chapter, a narrative review, in chapter 2, describes the unapparent effects of citrate anticoagulation in CRRT: on calcium, magnesium and phosphate balance, followed by hormonal (PTH and vitamin D) and inflammation and oxidative stress. Chapter 3 describes the effect of citrate dose in CVVH on calcium balance in a prospective study, randomising to low dose citrate or high dose citrate for 24 hours, using 100% postfilter calcium replacement. Extra physician-ordered Ca aimed at a systemic iCa > 1.0 mmol/L. A higher citrate dose caused a more negative CVVH Ca balance, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, resulted in a positive Ca-balance in both groups. At higher doses the calcium replacement algorithm, set at 100%, fell short. Intact (i)PTH decreased significantly over 24 hours, though biologically active non-oxidized PTH remained unchanged. All changes in iPTH over 24 hours were the consequence of a decrease in oxidized PTH, suggesting decreased in oxidative stress. 25-Vitamin D decreased while 1,25-Vitamin D rose. Chapter 4 explores the effects of differing anticoagulant regimes (citrate or heparin) in cell salvage in elective adult CABG. Red blood cell characteristics and inflammation were measured in the blood collection reservoir (BCR), washed red blood cell concentrate (WRBC) and postoperatively in the peripheral blood, before and after transfusion of WRBC. Higher IL-10 was found in the citrate group in the BCR, higher neutrophil-derived myeloperoxidase (MPO) in the heparin group after WRBC infusion, indicating differences in inflammatory effect of the coagulants. Chapter 5 examines the determinants of Total/ionized Calcium, a marker for citrate accumulation, in citrate CVVH, in a retrospective observational study. Citrate target and pH were the main independent predictors of T/iCa with albumin, phosphate and APACHE score as modifiers. Chapter 6 describes the effect of catheter port reversal in the setting of CVVH, in well-functioning catheters. Reversal caused a significant decrease in PfiCa and increase in PfCC, due to increased recirculation. Urea and creatinine clearances dropped significantly, but calcium clearance remained unaffected. Calcium handling differs from other solutes because of increases caused in citrate concentration and subsequent effects on calcium chelation
New insights in the enigma of nociception and pain assessment : an evaluation of integrated pain care pathways, digital opportunities and nociceptive reflex testing
No full textAbstract: Pain is a complex medical problem. Acute pain is typically initiated through a noxious stimulus, which causes the activation of specialized somatic or visceral nociceptors and transmission of nociceptive signals to the brain through spinal pathways. As pain persists, however, the underlying pathology may evolve to a chronic disease, amplifying the response to pain, decreasing treatment success, and often leading to sensitization. The negative physiologic and psychological consequences of unrelieved pain are significant and can be long-lasting with severe consequences on overall well-being. The stress response induced by pain may include increased heart and breathing rates affecting the increasing demand for oxygen and other nutrients to vital organs. A prolonged stress state can result in detrimental multisystem effects such as stiffness, loss of muscle and joint flexibility, sleeping difficulties, anxiety, and depression. Pain adversely affects the health-related quality of life and well-being, both in the short and long term. According to the US Centers for Disease Control and Prevention, prevalence rates of chronic pain vary between 11% and 40%. A systematic review comprising studies done in the UK reported a pooled chronic pain prevalence rate of 43.5%, with the rate of moderate-to-severe disabling pain ranging from 10.4% to 14.3%. The Global Burden of Disease Study 2019 reaffirmed that the high prominence of pain and pain-related diseases is still the leading cause of disability and disease burden globally [Lancet 2020 data 1990-2019]. This includes especially lower back pain and headache besides other musculoskeletal disorders but also underlines biopsychosocial predispositions (such as depression, anxiety, and opioid use disorders) for the development of other types of chronic pain including persistent postsurgical pain (PPSP). Improved pain measurements, especially in non-communicative patients, may be an important step in the prevention and early treatment of this debilitating disease. During the past decade many new, more objective pain assessment tools have been developed, driven by increased awareness of suboptimal pain assessment. However, these novel tools often lack proper validation for clinical use. Furthermore, daily routine use is usually rather complex. In addition, early identification of patients at risk of developing chronic (postsurgical) pain and including them in a patient-centric holistic perioperative care pathway, including physical and psychological functioning evaluation as well as patient satisfaction and wellbeing assessment, are essential for the prevention and treatment of chronic pain. This dissertation describes the development, implementation, and re-evaluation of transmural perioperative care pathways for individuals at risk for pain chronification, and how these can contribute to improved pain care. Furthermore, two objective nociceptive reflex assessment tools were validated during surgery and intensive care treatment, aiming to optimize nociceptive assessment. These two assessments embrace the greater goal of persistent pain prevention and optimal procedure-related pain treatment using a biopsychosocial approach. For monitoring nociception and pain in analgosedated patients, the novel pupillometric index (PPI) was designed to assess the level of intraoperative analgesia. We were among the first to evaluate the pupil dilation reflex (PDR) using a PPI protocol during routine surgical procedures in 2018 (chapter 3.1).1 After opioid administration, propofol-sedated patients needed a higher stimulation intensity to obtain a pupillary reflex in response to the standardized automated nociceptive stimulus. Consequently, PPI score showed a reduction after opioid analgetic treatment. Moreover, the elicitation of PDR by this low-intensity standardized noxious stimulation protocol was performed without changes in vital signs before and after opioid administration in adults under propofol-based general anesthesia (chapter 3.2). In addition, in children under general anesthesia, PPI assessments appeared to be feasible (chapter 3.3).2 Subsequently, PPI was further evaluated during surgical procedures under general anesthesia using sufentanil (chapter 3.4)3 and remifentanil (chapter 3.5)[ahead of print]. Both studies showed no additional value of an opioid administration protocol depending on PPI monitoring results in outpatient surgery. In sedated critically ill patients, PDR and nociception flexion reflex (NFR) are identified as non-invasive and well-tolerated monitoring tools (chapter 4.1).4 However, results regarding the shift from NFR threshold monitoring in a perioperative setting to the mechanically ventilated, analgosedated critically ill remains unclear. Furthermore, we focused on the design and implementation of holistic pain care for patients undergoing elective surgery. In our preliminary evaluation of a web-based psychological screening tool in adolescents undergoing minimally invasive pectus surgery (chapter 5.1)5, we showed that perioperative online screening of psychological symptoms and trait characteristics could further inventorize patients at risk for prolonged pain conditions. Moreover, we showed that allocating patients to the appropriate level of care preoperatively and immediately after surgery may improve long-term outcome variables (chapter 5.2).6 Internet-based technologies and feasible, objective monitoring tools can help clinicians screen surgical patients for risk factors and initiate early treatment if necessary (chapters 5.1 and 5.2).5,6 One of the major difficulties of integrated nociceptive evaluation in the analgosedated patient, in general, is that many devices are characterized by a laborious and often time-consuming set-up, making the translation from the clinical lab to daily practice cumbersome or even impossible. Nevertheless, they might have the potential to further improve individual pharmacological treatment and outcome measurements as intraoperative nociception monitoring guidance may reduce intraoperative opioid administration and therefore might be a viable strategy to titrate opioids intraoperatively.7 However, to date, there is a paucity of evidence regarding the impact of opioid minimization or total avoidance on long-term analgetic use and outcomes (chronic pain, functionality, wellbeing). Up to now, despite advances in nociception monitoring technology and availability in recent years, their limitations override their benefits in routine anesthesia care. Future research should focus on defining how the balance between nociception and analgesia may affect patient-related outcome measurements (PROMs), and consequently, identify a critical balance where we positively or negatively affect patient outcomes. Consecutively, timing, frequency, and amount of analgetic titration and its impact on patients\u2019 recovery can be evaluated. Additionally, when focusing on our patients\u2019 recovery, postoperative rehabilitation, and well-being should play a more central role as primary outcome parameters taking the entire biopsychosocial package into account, in contrast to solely focusing on nociceptive monitoring, which appears up to now to be just a drop in the ocean. When embracing the knowledge and know-how to design, implement and evaluate novel pain care pathways in real-world situations, interdisciplinary teams providing biopsychosocial care will better understand and combat the burden of chronic pain
Pre-admission air pollution exposure prolongs the duration of ventilation in intensive care patients
No full textPurpose Air pollutant exposure constitutes a serious risk factor for the emergence or aggravation of (existing) pulmonary disease. The impact of pre-intensive care ambient air pollutant exposure on the duration of artificial ventilation was, however, not yet established. Methods The medical records of 2003 patients, admitted to the intensive care unit (ICU) of the Antwerp University Hospital (Flanders, Belgium), who were artificially ventilated on ICU admission or within 48 h after admission, for the duration of at least 48 h, were analyzed. For each patient's home address, daily air pollutant exposure [particulate matter with an aerodynamic diameter <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10), nitrogen dioxide (NO2) and black carbon (BC)] up to 10 days prior to hospital admission was modeled using a high-resolution spatial-temporal model. The association between duration of artificial ventilation and air pollution exposure during the last 10 days before ICU admission was assessed using distributed lag models with a negative binomial regression fit. Results Controlling for pre-specified confounders, an IQR increment in BC (1.2 mu g/m(3)) up to 10 days before admission was associated with an estimated cumulative increase of 12.4% in ventilation duration (95% CI 4.7-20.7). Significant associations were also observed for PM2.5, PM10 and NO2, with cumulative estimates ranging from 7.8 to 8.0%. Conclusion Short-term ambient air pollution exposure prior to ICU admission represents an unrecognized environmental risk factor for the duration of artificial ventilation in the ICU.This study received no external funding. No entity other than the authors listed played any role in the design of the study; the collection, analysis or interpretation of data; the writing of the report; or in the decision to submit this paper for publication. All authors have full access to the data. Tim Nawrot is a beneficiary of the European Research Council. Bram Janssen and Bianca Cox are postdoctoral fellows of the Research Foundation-Flanders (FWO 12W3218N and 12Q0517N, respectively, and supported by FWO project G082317N). We would like to thank Hilde Fleurackers for the administrative support and assistance she provided.De Weerdt, A (reprint author), Antwerp Univ Hosp UZA, Dept Crit Care Med, Wilrijkstr 10, B-2650 Edegem, Belgium.
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Alkaline phosphatase treatment improves renal function in severe sepsis or septic shock patients
No full textAbstract: Objective: Alkaline phosphatase (AP) attenuates inflammatory responses by lipopolysaccharide detoxification and may prevent organ damage during sepsis. To investigate the effect of AP in patients with severe sepsis or septic shock on acute kidney injury. Design and Setting: A multicenter double-blind, randomized, placebo-controlled phase IIa study (2:1 ratio). Patients: Thirty-six intensive care unit patients (20 men/16 women, mean age 58 +/- 3 years) with a proven or suspected Gram-negative bacterial infection, >=2 systemic inflammatory response syndrome criteria (<24 hours), and <12 hours end-organ dysfunction onset were included. Intervention: An initial bolus intravenous injection (67.5 U/kg body weight) over 10 minutes of AP or placebo, followed by continuous infusion (132.5 U/kg) over the following 23 hours and 50 minutes. Measurements and Main Results: Median plasma creatinine levels declined significantly from 91 (73-138) to 70 (60-92) [mu]mol/L only after AP treatment. Pathophysiology of nitric oxide (NO) production and subsequent renal damage were assessed in a subgroup of 15 patients. A 42-fold induction (vs. healthy subjects) in renal inducible NO synthase expression was reduced by 80% +/- 5% after AP treatment. In AP-treated patients, the increase in cumulative urinary NO metabolite excretion was attenuated, whereas the opposite occurred after placebo. Reduced excretion of NO metabolites correlated with the proximal tubule injury marker glutathione S-transferase A1-1 in urine, which decreased by 70 (50-80)% in AP-treated patients compared with an increase by 200 (45-525)% in placebo-treated patients. Conclusions: In severe sepsis and septic shock, infusion of AP inhibits the upregulation of renal inducible NO synthase, leading to subsequent reduced NO metabolite production, and attenuated tubular enzymuria. This mechanism may account for the observed improvement in renal function
Harms and pitfalls of intravenous fluid therapy in the hospital
No full textAbstract: Introduction -The administration of intravenous fluid therapy is common in hospitalized patients but involves different risks. Particularly, the impact of both high sodium and chloride burdens is still unclear. Methods -Two retrospective \u201cbig data\u201d analyses. A cross-over study in healthy volunteers. A randomized controlled trial in the perioperative setting. A narrative review integrating additional results from the latter two studies. -The focus of this PhD thesis lies on the impact of isotonic compared to hypotonic maintenance fluids on fluid retention in health and the clinical setting. Physiological mechanisms are discussed. Results -We found a significant and consistent association between severe hyperchloremia (>110 mmol/L) and mortality. On the other hand, a low strong ion difference did not seem to be associated with deleterious effects. -We demonstrated that maintenance and replacement fluids accounted for a much larger part of the mean daily total fluid volume than resuscitation fluids and that they formed the most important source of sodium and chloride. We drew attention to the enormous part of daily fluid administration in the form of oral and intravenous medication and termed this large unintentional volume fluid creep. -Regarding maintenace fluid therapy, maintenance fluid therapy containing 154 mmol/L of sodium lead to lower urine output than hypotonic solutions containing 54 mmol/L of sodium in healthy volunteers. In a surgical population, we were able to demonstrate that maintenance fluids containing 154 mmol/L of sodium cause an importantly more positive cumulative fluid balance and substantial hyperchloremia than fluids with 54 mmol/L of sodium, revealing them as an independent cause of potentially detrimental fluid, sodium and chloride overload. Hyponatremia was encountered more frequently under the hypotonic solution but it was mostly mild and asymptomatic. -Even healthy kidneys deal inefficiently with the large sodium burdens that are typically administered to many hospitalized patients. Conclusion -Hyperchloremia is associated with mortality, but the absence of an association between a low strong ion difference and mortality warrants a careful interpretation when judging the value of balanced solutions based on findings on electrolyte disorders. -Based on our sodium studies, we advise to reduce unintentional sodium administration in the hospital and recommend hypotonic over isotonic maintenance fluid therapy (while avoiding any maintenance fluids when sufficient alternative fluid sources are being administered). Yet, patients at risk for developing hyponatremia deserve specific attention
Visualisatie, analyse en optimalisatie van individuele longmechanica
No full textAbstract: Mechanical ventilation, a universal therapy during general anaesthesia and in the critically il patient, has recently redemonstrated its significance and adaptability during the COVID-19 pandemic. Positive pressure ventilation itself, however, may inflict damage to the lungs. The objective of this dissertation is to enhance lung protective respiratory mechanics in contemporary clinical settings. In the first section, we investigated lung mechanics during laparoscopy in steep Trendelenburg position, which serves as a clinical model of a restrictive chest wall during passive ventilation. We have validated a method that allows for the reproducible measurement of end-expiratory transpulmonary pressure during surgical procedures. Our findings from a prospective clinical physiological crossover trial suggest that elevating PEEP beyond the guideline-recommended level enhances lung mechanics and oxygenation without inducing detrimental hyperinflation. In the second section, we explored mechanics during assisted positive pressure ventilation with spontaneous breathing efforts. The quantification of inspiratory effort during mechanical ventilation is of high relevance as it augments lung stress and often remains undetected. In a prospective clinical crossover trial, we compared the diaphragm thickening fraction with the gold standard oesophageal manometry as a measure for a range of inspiratory efforts in paediatric patients. Ultrasound was able to detect breathing efforts, but it was inadequate in quantifying the magnitude of these efforts, especially during rigorous breathing. Furthermore, we initiated a multicentre international prospective clinical trial in both adult and paediatric populations to determine the safe cutoffs at which lung- and diaphragm-protective ventilation during assistive positive pressure ventilation are balanced. In the third section, we examined the effects of controlled expiratory flow during flow-controlled ventilation on oxygenation and ventilation. In a pragmatic prospective crossover clinical trial on COVID-19 ARDS patients, we compared conventional volume-controlled ventilation with flow-controlled ventilation. Contrary to expectations, our findings suggest that oxygenation does not differ, but ventilation is enhanced during flow-controlled ventilation. Subsequently, we validated volumetric capnography as a method to measure dead space ventilation during controlled expiratory flow in a bench test. Lastly, we designed a prospective clinical trial to study dead space ventilation in homogenous lungs during mandatory flow-controlled ventilation, hypothesizing that the improvement in ventilation is attributable to a reduction in dead space. Further refinement of mechanical ventilation as an indispensable lifesaving therapy should focus on the clinical quantification of the balance between lung-and diaphragm protective ventilation and the reduction of dead space ventilation
Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach : the INSIGHT FLU 002 and FLU 003 studies
No full textAbstract: The novel pandemic influenza A (H1H1) 2009 virus spread rapidly around the world in 2009. The paucity of prospective international epidemiologic data on predictors of clinical outcomes with pandemic (H1N1) 2009 virus infection stimulated the INSIGHT network, an international network of community and hospital-based investigators, to commence two worldwide clinical observational studies to describe pandemic (H1N1) 2009 virus activity. The purpose of these two studies was to estimate the percent of adult patients with illness due to laboratory-confirmed pandemic (H1N1) 2009 virus infection that experience clinically significant outcomes and to study factors related to these outcomes. Enrollment commenced in October 2009 and will continue until August 2011: as of the end of 2010, 62 sites in 14 countries in Australasia (12 sites), Europe (37) and North America (13) have enrolled 1365 adult patients, with 1049 enrollments into the FLU 002 outpatient study and 316 into the FLU 003 hospitalization study. These in progress INSIGHT influenza observational studies may act as a model for obtaining epidemiological, clinical and laboratory information in future international disease outbreaks
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