Publications by authors named "Marcus J Schultz"

654 Publications

High Mobility Group Box 1 and Interleukin 6 at Intensive Care Unit Admission as Biomarkers in Critically Ill COVID-19 Patients.

Am J Trop Med Hyg 2021 May 3. Epub 2021 May 3.

10School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand.

Exuberant inflammation manifesting as a "cytokine storm" has been suggested as a central feature in the pathogenesis of severe coronavirus disease 2019 (COVID-19). This study investigated two prognostic biomarkers, the high mobility group box 1 (HMGB1) and interleukin-6 (IL-6), in patients with severe COVID-19 at the time of admission in the intensive care unit (ICU). Of 60 ICU patients with COVID-19 enrolled and analyzed in this prospective cohort study, 48 patients (80%) were alive at ICU discharge. HMGB1 and IL-6 plasma levels at ICU admission were elevated compared with a healthy control, both in ICU nonsurvivors and ICU survivors. HMGB1 and IL-6 plasma levels were higher in patients with a higher Sequential Organ Failure Assessment (SOFA) score (> 10), and the presence of septic shock or acute kidney injury. HMGB1 and IL-6 plasma levels were also higher in patients with a poor oxygenation status (PaO2/FiO2 < 150 mm Hg) and a longer duration of ventilation (> 7 days). Plasma HMGB1 and IL-6 levels at ICU admission also correlated with other prognostic markers, including the maximum neutrophil/lymphocyte ratio, D-dimer levels, and C-reactive protein levels. Plasma HMGB1 and IL-6 levels at ICU admission predicted ICU mortality with comparable accuracy to the SOFA score and the COVID-GRAM risk score. Higher HMGB1 and IL-6 were not independently associated with ICU mortality after adjustment for age, gender, and comorbidities in multivariate analysis models. In conclusion, plasma HMGB1 and IL6 at ICU admission may serve as prognostic biomarkers in critically ill COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.21-0165DOI Listing
May 2021

Plasma Ferritin as Marker of Macrophage Activation-Like Syndrome in Critically Ill Patients With Community-Acquired Pneumonia.

Crit Care Med 2021 May 3. Epub 2021 May 3.

Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands. Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands. Respiratory Medicine and Experimental Immunology, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands. Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands. Julius Center for Health Sciences and Primary Care, University of Utrecht, Utrecht, The Netherlands. Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands. Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand. Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands. Division of Infectious Diseases, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, Amsterdam, The Netherlands.

Objectives: Plasma ferritin levels above 4,420 ng/mL have been proposed as a diagnostic marker for macrophage activation-like syndrome in sepsis and used for selection of sepsis patients for anti-inflammatory therapy. We here sought to determine the frequency, presentation, outcome, and host response aberrations of macrophage activation-like syndrome, as defined by admission ferritin levels above 4,420 ng/mL, in critically ill patients with community-acquired pneumonia.

Design: A prospective observational cohort study.

Setting: ICUs in two tertiary hospitals in the Netherlands.

Patients: One hundred fifty-three patients admitted with community-acquired pneumonia.

Measurements And Main Results: Patients were stratified in community-acquired pneumonia-macrophage activation-like syndrome (n = 15; 9.8%) and community-acquired pneumonia-control groups (n = 138; 90.2%) based on an admission plasma ferritin level above or below 4,420 ng/mL, respectively. Community-acquired pneumonia-macrophage activation-like syndrome patients presented with a higher disease severity and had a higher ICU mortality (46.7% vs 12.3% in community-acquired pneumonia-controls; p = 0.002). Twenty-three plasma biomarkers indicative of dysregulation of key host response pathways implicated in sepsis pathogenesis (systemic inflammation, cytokine responses, endothelial cell activation, and barrier function, coagulation activation) were more disturbed in community-acquired pneumonia-macrophage activation-like syndrome patients. Hematologic malignancies were overrepresented in community-acquired pneumonia-macrophage activation-like syndrome patients (33.3% vs 5.1% in community-acquired pneumonia-controls; p = 0.001). In a subgroup analysis excluding patients with hematologic malignancies (n = 141), differences in mortality were not present anymore, but the exaggerated host response abnormalities in community-acquired pneumonia-macrophage activation-like syndrome patients remained.

Conclusions: Macrophage activation-like syndrome in critically ill patients with community-acquired pneumonia occurs more often in patients with hematologic malignancies and is associated with deregulation of multiple host response pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000005072DOI Listing
May 2021

How to monitor cardiovascular function in critical illness in resource-limited settings.

Curr Opin Crit Care 2021 Apr 22. Epub 2021 Apr 22.

Department of Clinical Tropical Medicine Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University, Bangkok, Thailand Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.

Purpose Of Review: Hemodynamic monitoring is an essential component in the care for critically ill patients. A range of tools are available and new approaches have been developed. This review summarizes their availability, affordability and feasibility for hospital settings in resource-limited settings.

Recent Findings: Evidence for the performance of specific hemodynamic monitoring tools or strategies in low-income and middle-income countries (LMICs) is limited. Repeated physical examination and basic observations remain a cornerstone for patient monitoring and have a high sensitivity for detecting organ hypoperfusion, but with a low specificity. Additional feasible approaches for hemodynamic monitoring in LMICs include: for tissue perfusion monitoring: urine output, skin mottling score, capillary refill time, skin temperature gradients, and blood lactate measurements; for cardiovascular monitoring: echocardiography and noninvasive or minimally invasive cardiac output measurements; and for fluid status monitoring: inferior vena cava distensibility index, mini-fluid challenge test, passive leg raising test, end-expiratory occlusion test and lung ultrasound. Tools with currently limited applicability in LMICs include microcirculatory monitoring devices and pulmonary artery catheterization, because of costs and limited added value. Especially ultrasound is a promising and affordable monitoring device for LMICs, and is increasingly available.

Summary: A set of basic tools and approaches is available for adequate hemodynamic monitoring in resource-limited settings. Future research should focus on the development and trialing of robust and context-appropriate monitoring technologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCC.0000000000000830DOI Listing
April 2021

How to monitor cardiovascular function in critical illness in resource-limited settings.

Curr Opin Crit Care 2021 Jun;27(3):274-281

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine Mahidol University, Bangkok, Thailand.

Purpose Of Review: Hemodynamic monitoring is an essential component in the care for critically ill patients. A range of tools are available and new approaches have been developed. This review summarizes their availability, affordability and feasibility for hospital settings in resource-limited settings.

Recent Findings: Evidence for the performance of specific hemodynamic monitoring tools or strategies in low-income and middle-income countries (LMICs) is limited. Repeated physical examination and basic observations remain a cornerstone for patient monitoring and have a high sensitivity for detecting organ hypoperfusion, but with a low specificity. Additional feasible approaches for hemodynamic monitoring in LMICs include: for tissue perfusion monitoring: urine output, skin mottling score, capillary refill time, skin temperature gradients, and blood lactate measurements; for cardiovascular monitoring: echocardiography and noninvasive or minimally invasive cardiac output measurements; and for fluid status monitoring: inferior vena cava distensibility index, mini-fluid challenge test, passive leg raising test, end-expiratory occlusion test and lung ultrasound. Tools with currently limited applicability in LMICs include microcirculatory monitoring devices and pulmonary artery catheterization, because of costs and limited added value. Especially ultrasound is a promising and affordable monitoring device for LMICs, and is increasingly available.

Summary: A set of basic tools and approaches is available for adequate hemodynamic monitoring in resource-limited settings. Future research should focus on the development and trialing of robust and context-appropriate monitoring technologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCC.0000000000000830DOI Listing
June 2021

Induced normothermia ameliorates the procoagulant host response in human endotoxaemia.

Br J Anaesth 2021 Apr 23. Epub 2021 Apr 23.

Laboratory of Experimental Intensive Care and Anaesthesiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Department of Intensive Care Medicine, OLVG Hospital, Amsterdam, the Netherlands.

Background: Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers.

Methods: Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model.

Results: In control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x10 L([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide.

Conclusion: In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bja.2021.02.033DOI Listing
April 2021

Quantifying the Effect of Lower vs Higher Positive End-Expiratory Pressure on Ventilator-Free Survival in ICU Patients-Reply.

JAMA 2021 04;325(15):1567-1568

Department of Intensive Care, Amsterdam University Medical Centers, Amsterdam, the Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2021.1703DOI Listing
April 2021

Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis.

Clin Exp Immunol 2021 Apr 18. Epub 2021 Apr 18.

Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Sepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (gzm) are proteases mainly found in cytotoxic lymphocytes, that not only have a role in target cell death, but also as mediators of infection and inflammation. We here sought to analyse the intracellular expression of gzm A, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected ICU patients and 32 healthy controls. Additionally, we measured gzmA and B plasma levels. Both groups of patients presented decreased percentage of NK cells expressing gzmA, gzmB and gzmM relative to healthy controls, while sepsis patients showed an increased proportion of CD8 T cells expressing gzmB compared to controls. Expression of gzmK remained relatively unaltered between groups. Extracellular levels of gzmB were increased in non-infected ICU patients relative to sepsis patients and to healthy controls. Our results show differential alterations in intracellular expression of gzm in sepsis patients and non-infected critically ill patients compared to healthy individuals depending on the lymphocyte population and on the gzm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cei.13601DOI Listing
April 2021

Ventilation management in acute respiratory failure related to COVID-19 versus ARDS from another origin - a descriptive narrative review.

Expert Rev Respir Med 2021 Apr 13:1-11. Epub 2021 Apr 13.

Department of Intensive Care, Amsterdam University Medical Centers, location 'AMC', Amsterdam, The Netherlands.

Introduction: It is uncertain whether ventilation in patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) differs from that in patients with acute respiratory distress syndrome (ARDS) from another origin.

Areas Covered: We undertook two literature searches in PubMed to identify observational studies reporting on ventilation management--one in patients with acute respiratory failure related to COVID-19, and one in patients with ARDS from another origin. The searches identified 14 studies in patients with acute respiratory failure related to COVID-19, and 8 studies in patients with ARDS from another origin.

Expert Opinion: In patients with acute respiratory failure related to COVID-19, ventilation management seems to be similar to that of patients with ARDS from another origin. The future lies in studies focused on personalized treatment of ARDS of all origins, including COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17476348.2021.1913060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054495PMC
April 2021

Individualized versus Fixed Positive End-expiratory Pressure for Intraoperative Mechanical Ventilation in Obese Patients: A Secondary Analysis.

Anesthesiology 2021 Apr 12. Epub 2021 Apr 12.

Background: General anesthesia may cause atelectasis and deterioration in oxygenation in obese patients. The authors hypothesized that individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and ventilation distribution compared to fixed PEEP.

Methods: This secondary analysis included all obese patients recruited at University Hospital of Leipzig from the multicenter Protective Intraoperative Ventilation with Higher versus Lower Levels of Positive End-Expiratory Pressure in Obese Patients (PROBESE) trial (n = 42) and likewise all obese patients from a local single-center trial (n = 54). Inclusion criteria for both trials were elective laparoscopic abdominal surgery, body mass index greater than or equal to 35 kg/m2, and Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score greater than or equal to 26. Patients were randomized to PEEP of 4 cm H2O (n = 19) or a recruitment maneuver followed by PEEP of 12 cm H2O (n = 21) in the PROBESE study. In the single-center study, they were randomized to PEEP of 5 cm H2O (n = 25) or a recruitment maneuver followed by individualized PEEP (n = 25) determined by electrical impedance tomography. Primary endpoint was Pao2/inspiratory oxygen fraction before extubation and secondary endpoints included intraoperative tidal volume distribution to dependent lung and driving pressure.

Results: Ninety patients were evaluated in three groups after combining the two lower PEEP groups. Median individualized PEEP was 18 (interquartile range, 16 to 22; range, 10 to 26) cm H2O. Pao2/inspiratory oxygen fraction before extubation was 515 (individual PEEP), 370 (fixed PEEP of 12 cm H2O), and 305 (fixed PEEP of 4 to 5 cm H2O) mmHg (difference to individualized PEEP, 145; 95% CI, 91 to 200; P < 0.001 for fixed PEEP of 12 cm H2O and 210; 95% CI, 164 to 257; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Intraoperative tidal volume in the dependent lung areas was 43.9% (individualized PEEP), 25.9% (fixed PEEP of 12 cm H2O) and 26.8% (fixed PEEP of 4 to 5 cm H2O) (difference to individualized PEEP: 18.0%; 95% CI, 8.0 to 20.7; P < 0.001 for fixed PEEP of 12 cm H2O and 17.1%; 95% CI, 10.0 to 20.6; P < 0.001 for fixed PEEP of 4 to 5 cm H2O). Mean intraoperative driving pressure was 9.8 cm H2O (individualized PEEP), 14.4 cm H2O (fixed PEEP of 12 cm H2O), and 18.8 cm H2O (fixed PEEP of 4 to 5 cm H2O), P < 0.001.

Conclusions: This secondary analysis of obese patients undergoing laparoscopic surgery found better oxygenation, lower driving pressures, and redistribution of ventilation toward dependent lung areas measured by electrical impedance tomography using individualized PEEP. The impact on patient outcome remains unclear.

Editor’s Perspective:
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0000000000003762DOI Listing
April 2021

Case Studies in Physiology: Physiological and clinical effects of temporary diaphragm pacing in 2 patients with ventilator-induced diaphragm dysfunction.

J Appl Physiol (1985) 2021 Apr 8. Epub 2021 Apr 8.

Critical Care, Hospital Universitario de Getafe, Spain.

IntroductionVentilator-induced diaphragm dysfunction (VIDD) is increasingly recognized as an important side-effect of invasive ventilation in critically ill patients and is associated with poor outcomes. Whether patients with VIDD benefit from temporary diaphragm pacing is uncertain.Material and MethodsIntramuscular diaphragmatic electrodes were implanted for temporary stimulation with a pacing device (TransAeris{trade mark, serif} System) in two patients with VIDD. The electrodes were implanted via laparoscopy (first patient), or via bilateral thoracoscopy (second patient). Stimulation parameters were titrated according to tolerance. Diaphragm thickening fraction by ultrasound, maximum inspiratory pressure (Pi) and diaphragm electromyography (EMGdi) signal analysis were used to monitor the response to diaphragm pacing.ResultsBoth patients tolerated diaphragm pacing. In the first patient improvements in diaphragm excursions were noted once pacing was initiated, and diaphragm thickening fraction did not further deteriorate over time. The diaphragm thickening fraction improved in the second patient, and Pi as well as EMGdi analysis suggested improved muscle function. This patient could be fully weaned from the ventilator.DiscussionThese case reports present the first experience with temporary diaphragm pacing in critically ill patients with VIDD. Our results should be taken cautiously given the reduced sample size, but provide the proof of concept to put forward the hypothesis that a course of diaphragm pacing may be associated with improved diaphragmatic function. Our findings of the tolerance to the procedure and the beneficial physiological effects are not prove of safety and efficacy, but may set the ground to design and conduct larger studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/japplphysiol.00543.2020DOI Listing
April 2021

Associations of Body Mass Index with Ventilation Management and Clinical Outcomes in Invasively Ventilated Patients with ARDS Related to COVID-19-Insights from the PRoVENT-COVID Study.

J Clin Med 2021 03 11;10(6). Epub 2021 Mar 11.

Department of Intensive Care, Amsterdam UMC, Location AMC, 1105 AZ Amsterdam, The Netherlands.

We describe the practice of ventilation and mortality rates in invasively ventilated normal-weight (18.5 ≤ BMI ≤ 24.9 kg/m), overweight (25.0 ≤ BMI ≤ 29.9 kg/m), and obese (BMI > 30 kg/m) COVID-19 ARDS patients in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. The primary outcome was a combination of ventilation variables and parameters over the first four calendar days of ventilation, including tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure in normal-weight, overweight, and obese patients. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and mortality rates. Between 1 March 2020 and 1 June 2020, 1122 patients were included in the study: 244 (21.3%) normal-weight patients, 531 (47.3%) overweight patients, and 324 (28.8%) obese patients. Most patients received a tidal volume < 8 mL/kg PBW; only on the first day was the tidal volume higher in obese patients. PEEP and driving pressure were higher, and compliance of the respiratory system was lower in obese patients on all four days. Adjunctive therapies for refractory hypoxemia were used equally in the three BMI groups. Adjusted mortality rates were not different between BMI categories. The findings of this study suggest that lung-protective ventilation with a lower tidal volume and prone positioning is similarly feasible in normal-weight, overweight, and obese patients with ARDS related to COVID-19. A patient's BMI should not be used in decisions to forgo or proceed with invasive ventilation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10061176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000207PMC
March 2021

The Association of Intraoperative driving pressure with postoperative pulmonary complications in open versus closed abdominal surgery patients - a posthoc propensity score-weighted cohort analysis of the LAS VEGAS study.

BMC Anesthesiol 2021 Mar 19;21(1):84. Epub 2021 Mar 19.

Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, Amsterdam, The Netherlands.

Background: It is uncertain whether the association of the intraoperative driving pressure (ΔP) with postoperative pulmonary complications (PPCs) depends on the surgical approach during abdominal surgery. Our primary objective was to determine and compare the association of time-weighted average ΔP (ΔP) with PPCs. We also tested the association of ΔP with intraoperative adverse events.

Methods: Posthoc retrospective propensity score-weighted cohort analysis of patients undergoing open or closed abdominal surgery in the 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study, that included patients in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs. The secondary endpoint was a composite of intraoperative adverse events.

Results: The analysis included 1128 and 906 patients undergoing open or closed abdominal surgery, respectively. The PPC rate was 5%. ΔP was lower in open abdominal surgery patients, but ΔP was not different between groups. The association of ΔP with PPCs was significant in both groups and had a higher risk ratio in closed compared to open abdominal surgery patients (1.11 [95%CI 1.10 to 1.20], P <  0.001 versus 1.05 [95%CI 1.05 to 1.05], P <  0.001; risk difference 0.05 [95%CI 0.04 to 0.06], P <  0.001). The association of ΔP with intraoperative adverse events was also significant in both groups but had higher odds ratio in closed compared to open abdominal surgery patients (1.13 [95%CI 1.12- to 1.14], P <  0.001 versus 1.07 [95%CI 1.05 to 1.10], P <  0.001; risk difference 0.05 [95%CI 0.030.07], P <  0.001).

Conclusions: ΔP is associated with PPC and intraoperative adverse events in abdominal surgery, both in open and closed abdominal surgery.

Trial Registration: LAS VEGAS was registered at clinicaltrials.gov (trial identifier NCT01601223 ).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12871-021-01268-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977277PMC
March 2021

Checklist for Early Recognition and Treatment of Acute Illness and Injury: An Exploratory Multicenter International Quality-Improvement Study in the ICUs With Variable Resources.

Crit Care Med 2021 Feb 23. Epub 2021 Feb 23.

1 The Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia. 2 Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. 3 Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN. 4 Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. 5 Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 6 Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. 7 Department of Intensive Care, Amsterdam University Medical Centers, Amsterdam, The Netherlands. 8 Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Amsterdam University Medical Centers, Amsterdam, The Netherlands. 9 Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand. 10Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. 11 Department of Intensive Care, King Abdullah International Medical Research Center (KAIMRC), College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Kingdom of Saudi Arabia. 12 Multidisciplinary Intensive Care Research Organization, St James's Hospital, Dublin, Ireland. 13 Department of Pulmonology, Hospital Clínic de Barcelona, Universitat de Barcelona and IDIBAPS, Barcelona, Spain. 14 Centro de Investigación Biomédica en Red (CIBER), University of Barcelona, Barcelona, Spain. 15 Centro De Diagnostica Imagenes Medicina Avanzaday, Telemedicina CEDIMAT, Santo Domingo, Dominican Republic. 16 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN.

Objectives: To determine whether the "Checklist for Early Recognition and Treatment of Acute Illness and Injury" decision support tool during ICU admission and rounding is associated with improvements in nonadherence to evidence-based daily care processes and outcomes in variably resourced ICUs.

Design, Settings, Patients: This before-after study was performed in 34 ICUs (15 countries) from 2013 to 2017. Data were collected for 3 months before and 6 months after Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation.

Interventions: Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation using remote simulation training.

Measurements And Main Results: The coprimary outcomes, modified from the original protocol before data analysis, were nonadherence to 10 basic care processes and ICU and hospital length of stay. There were 1,447 patients in the preimplementation phase and 2,809 patients in the postimplementation phase. After adjusting for center effect, Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation was associated with reduced nonadherence to care processes (adjusted incidence rate ratio [95% CI]): deep vein thrombosis prophylaxis (0.74 [0.68-0.81), peptic ulcer prophylaxis (0.46 [0.38-0.57]), spontaneous breathing trial (0.81 [0.76-0.86]), family conferences (0.86 [0.81-0.92]), and daily assessment for the need of central venous catheters (0.85 [0.81-0.90]), urinary catheters (0.84 [0.80-0.88]), antimicrobials (0.66 [0.62-0.71]), and sedation (0.62 [0.57-0.67]). Analyses adjusted for baseline characteristics showed associations of Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation with decreased ICU length of stay (adjusted ratio of geometric means [95% CI]) 0.86 [0.80-0.92]), hospital length of stay (0.92 [0.85-0.97]), and hospital mortality (adjusted odds ratio [95% CI], 0.81 (0.69-0.95).

Conclusions: A quality-improvement intervention with remote simulation training to implement a decision support tool was associated with decreased nonadherence to daily care processes, shorter length of stay, and decreased mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004937DOI Listing
February 2021

Integrative Transkingdom Analysis of the Gut Microbiome in Antibiotic Perturbation and Critical Illness.

mSystems 2021 Mar 16;6(2). Epub 2021 Mar 16.

Center for Experimental and Molecular Medicine, Amsterdam UMC, Location AMC, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.

Bacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, and protozoa, are closely interlinked with the bacterial microbiota and their host, yet their collective role during antibiotic perturbation and critical illness remains to be elucidated. We employed multi-omics factor analysis (MOFA) to systematically integrate the bacterial (16S rRNA), fungal (intergenic transcribed spacer 1 rRNA), and viral (virus discovery next-generation sequencing) components of the intestinal microbiota of 33 critically ill patients with and without sepsis and 13 healthy volunteers. In addition, we quantified the absolute abundances of bacteria and fungi using 16S and 18S rRNA PCRs and characterized the short-chain fatty acids (SCFAs) butyrate, acetate, and propionate using nuclear magnetic resonance spectroscopy. We observe that a loss of the anaerobic intestinal environment is directly correlated with an overgrowth of aerobic pathobionts and their corresponding bacteriophages as well as an absolute enrichment of opportunistic yeasts capable of causing invasive disease. We also observed a strong depletion of SCFAs in both disease states, which was associated with an increased absolute abundance of fungi with respect to bacteria. Therefore, these findings illustrate the complexity of transkingdom changes following disruption of the intestinal bacterial microbiome. While numerous studies have characterized antibiotic-induced disruptions of the bacterial microbiome, few studies describe how these disruptions impact the composition of other kingdoms such as viruses, fungi, and protozoa. To address this knowledge gap, we employed MOFA to systematically integrate viral, fungal, and bacterial sequence data from critically ill patients (with and without sepsis) and healthy volunteers, both prior to and following exposure to broad-spectrum antibiotics. In doing so, we show that modulation of the bacterial component of the microbiome has implications extending beyond this kingdom alone, enabling the overgrowth of potentially invasive fungi and viruses. While numerous preclinical studies have described similar findings , we confirm these observations in humans using an integrative analytic approach. These findings underscore the potential value of multi-omics data integration tools in interrogating how different components of the microbiota contribute to disease states. In addition, our findings suggest that there is value in further studying potential adjunctive therapies using anaerobic bacteria or SCFAs to reduce fungal expansion after antibiotic exposure, which could ultimately lead to improved outcomes in the intensive care unit (ICU).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSystems.01148-20DOI Listing
March 2021

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

Crit Care 2021 03 16;25(1):106. Epub 2021 Mar 16.

Manchester University NHS Foundation Trust, Manchester, UK.

Background: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice.

Methods: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ) test (p < 0·05 was considered as unstable).

Results: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment.

Conclusion: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited.

Trial Registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-021-03491-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962430PMC
March 2021

Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers.

Am J Trop Med Hyg 2021 Mar 11. Epub 2021 Mar 11.

1Department of Intensive Care, Amsterdam University Medical Centers, Location 'AMC', Amsterdam, The Netherlands.

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.20-1445DOI Listing
March 2021

Effects of Lung Ultrasonography-Guided Management on Cumulative Fluid Balance and Other Clinical Outcomes: A Systematic Review.

Ultrasound Med Biol 2021 May 23;47(5):1163-1171. Epub 2021 Feb 23.

Department of Intensive Care, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands; Amsterdam Leiden IC Focused Echography, Amsterdam, The Netherlands.

Lung ultrasonography is accurate in detecting pulmonary edema and overcomes most limitations of traditional diagnostic modalities. Whether use of lung ultrasonography-guided management has an effect on cumulative fluid balances and other clinical outcomes remains unclear. In this systematic review, we included 12 studies using ultrasonography guided-management with a total of 2290 patients. Four in-patient studies found a reduced cumulative fluid balance (ranging from -0.3 L to -2.4 L), whereas three out-patient studies found reduction in dialysis dry weight (ranging from -2.6 kg to -0.2 kg) compared with conventionally managed patients. None of the studies found adverse effects related to hypoperfusion. The use of lung ultrasonography-guided management was not associated with other clinical outcomes. This systematic review shows that lung ultrasonography-guided management, exclusively or in concert with other diagnostic modalities, is associated with a reduced cumulative fluid balance. Studies thus far have not shown a consistent effect on clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultrasmedbio.2021.01.024DOI Listing
May 2021

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study.

Eur J Anaesthesiol 2021 02 16. Epub 2021 Feb 16.

From the Department of Intensive Care (SGN, LH, PS, ASN, JMB, MJS), Department of Anaesthesiology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands (SGN, LH, SNTH, MWH), Department of Critical Care Medicine, Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Monash University, Melbourne, Victoria, Australia (ASN), Hedenstierna Laboratory, Department of Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden (GH), Intensive Care Unit, University Hospital of Montpellier and Saint Eloi Hospital, Montpellier University, Montpellier, France (SJ), Division of Cardiac, Thoracic, Vascular Anaesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria (MH, WS), Operating Services, Critical Care and Anaesthesia, Sheffield Teaching Hospitals, Sheffield and University of Sheffield, Sheffield, UK (GHM), Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA (MFVM), Department of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany (CP), Department of Biotechnology and Life Sciences, ASST Sette Laghi Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy (PS), Department of Anaesthesiology, Intensive Care Medicine and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, Halle (HW), Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany (MG de A), Dipartimento di Scienze Chirurgiche e Diagnostiche Integrate, Università degli Studi di Genova (PP), IRCCS, Ospedale Policlinico San Martino, Genova, Italy (PP), Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand (MJS) and Nuffield Department of Medicine, University of Oxford, Oxford, UK (MJS).

Background: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.

Objectives: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.

Design, Patients And Setting: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.

Main Outcome Measures: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.

Results: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.

Conclusion: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.

Trial Registration: The study was registered at Clinicaltrials.gov, NCT01601223.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EJA.0000000000001476DOI Listing
February 2021

Comparison of Mechanical Power During Adaptive Support Ventilation Versus Nonautomated Pressure-Controlled Ventilation-A Pilot Study.

Crit Care Explor 2021 Feb 15;3(2):e0335. Epub 2021 Feb 15.

Department of Intensive Care, Reinier de Graaf Hospital, Delft, the Netherlands.

Objectives: The aim of this pilot study was to compare the amount of "mechanical power of ventilation" under adaptive support ventilation with nonautomated pressure-controlled ventilation.

Design: Single-center, observational prospective pilot study adjoining unitwide implementation of adaptive support ventilation in our department.

Setting: The ICU of a nonacademic teaching hospital in the Netherlands.

Patients: Twenty-four passive invasively ventilated critically ill patients expected to need of invasive ventilation beyond the following calendar day.

Measurements And Main Results: In patients under adaptive support ventilation, only positive end-expiratory pressure and Fio were set by the caregivers-all other ventilator settings were under control of the ventilator; in patients under pressure-controlled ventilation, maximum airway pressure (Pmax), positive end-expiratory pressure, Fio, and respiratory rate were set by the caregivers. Mechanical power of ventilation was calculated three times per day. Compared with pressure-controlled ventilation, mechanical power of ventilation with adaptive support ventilation was lower (15.1 [10.5-25.7] vs 22.9 [18.7-28.8] J/min; = 0.04). Tidal volume was not different, but Pmax ( = 0.012) and respiratory rate ( = 0.012) were lower with adaptive support ventilation.

Conclusions: This study suggests adaptive support ventilation may have benefits compared with pressure-controlled ventilation with respect to the mechanical power of ventilation transferred from the ventilator to the respiratory system in passive invasively ventilated critically ill patients. The difference in mechanical power of ventilation is not a result of a difference in tidal volume, but the reduction in applied pressures and respiratory rate. The findings of this observational pilot study need to be confirmed in a larger, preferably randomized clinical trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCE.0000000000000335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886404PMC
February 2021

Remote-Controlled and Pulse Pressure-Guided Fluid Treatment for Adult Patients with Viral Hemorrhagic Fevers.

Am J Trop Med Hyg 2021 Feb 16. Epub 2021 Feb 16.

1Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Circulatory shock, caused by severe intravascular volume depletion resulting from gastrointestinal losses and profound capillary leak, is a common clinical feature of viral hemorrhagic fevers, including Ebola virus disease, Marburg hemorrhagic fever, and Lassa fever. These conditions are associated with high case fatality rates, and they carry a significant risk of infection for treating personnel. Optimized fluid therapy is the cornerstone of management of these diseases, but there are few data on the extent of fluid losses and the severity of the capillary leak in patients with VHFs, and no specific guidelines for fluid resuscitation and hemodynamic monitoring exist. We propose an innovative approach for monitoring VHF patients, in particular suited for low-resource settings, facilitating optimizing fluid therapy through remote-controlled and pulse pressure-guided fluid resuscitation. This strategy would increase the capacity for adequate supportive care, while decreasing the risk for virus transmission to health personnel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.20-1515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045617PMC
February 2021

Biological subphenotypes of acute respiratory distress syndrome may not reflect differences in alveolar inflammation.

Physiol Rep 2021 Feb;9(3):e14693

Department of Intensive Care, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands.

Biological subphenotypes have been identified in acute respiratory distress syndrome (ARDS) based on two parsimonious models: the "uninflamed" and "reactive" subphenotype (cluster-model) and "hypo-inflammatory" and "hyper-inflammatory" (latent class analysis (LCA) model). The distinction between the subphenotypes is mainly driven by inflammatory and coagulation markers in plasma. However, systemic inflammation is not specific for ARDS and it is unknown whether these subphenotypes also reflect differences in the alveolar compartment. Alveolar inflammation and dysbiosis of the lung microbiome have shown to be important mediators in the development of lung injury. This study aimed to determine whether the "reactive" or "hyper-inflammatory" biological subphenotype also had higher concentrations of inflammatory mediators and enrichment of gut-associated bacteria in the lung. Levels of alveolar inflammatory mediators myeloperoxidase (MPO), surfactant protein D (SPD), interleukin (IL)-1b, IL-6, IL-10, IL-8, interferon gamma (IFN-ƴ), and tumor necrosis factor-alpha (TNFα) were determined in the mini-BAL fluid. Key features of the lung microbiome were measured: bacterial burden (16S rRNA gene copies/ml), community diversity (Shannon Diversity Index), and community composition. No statistically significant differences between the "uninflamed" and "reactive" ARDS subphenotypes were found in a selected set of alveolar inflammatory mediators and key features of the lung microbiome. LCA-derived subphenotypes and stratification based on cause of ARDS (direct vs. indirect) showed similar profiles, suggesting that current subphenotypes may not reflect the alveolar host response. It is important for future research to elucidate the pulmonary biology within each subphenotype properly, which is arguably a target for intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865405PMC
February 2021

Precision medicine in acute respiratory distress syndrome: workshop report and recommendations for future research.

Eur Respir Rev 2021 Mar 2;30(159). Epub 2021 Feb 2.

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Dept of Medicine, University of California, San Francisco, CA, USA.

Acute respiratory distress syndrome (ARDS) is a devastating critical illness that can be triggered by a wide range of insults and remains associated with a high mortality of around 40%. The search for targeted treatment for ARDS has been disappointing, possibly due to the enormous heterogeneity within the syndrome. In this perspective from the European Respiratory Society research seminar on "Precision medicine in ARDS", we will summarise the current evidence for heterogeneity, explore the evidence in favour of precision medicine and provide a roadmap for further research in ARDS. There is evident variation in the presentation of ARDS on three distinct levels: 1) aetiological; 2) physiological and 3) biological, which leads us to the conclusion that there is no typical ARDS. The lack of a common presentation implies that intervention studies in patients with ARDS need to be phenotype aware and apply a precision medicine approach in order to avoid the lack of success in therapeutic trials that we faced in recent decades. Deeper phenotyping and integrative analysis of the sources of variation might result in identification of additional treatable traits that represent specific pathobiological mechanisms, or so-called endotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/16000617.0317-2020DOI Listing
March 2021

Pragmatic Recommendations for the Management of Acute Respiratory Failure and Mechanical Ventilation in Patients with COVID-19 in Low- and Middle-Income Countries.

Am J Trop Med Hyg 2021 Jan 13. Epub 2021 Jan 13.

3Department of Intensive Care, Amsterdam University Medical Centers, Location 'Academic Medical Center', Amsterdam, The Netherlands.

Management of patients with severe or critical COVID-19 is mainly modeled after care for patients with severe pneumonia or acute respiratory distress syndrome (ARDS) from other causes, and these recommendations are based on evidence that often originates from investigations in resource-rich intensive care units located in high-income countries. Often, it is impractical to apply these recommendations to resource-restricted settings, particularly in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for acute respiratory failure and mechanical ventilation management in patients with severe/critical COVID-19 in LMICs. We suggest starting supplementary oxygen when SpO2 is persistently lower than 94%. We recommend supplemental oxygen to keep SpO2 at 88-95% and suggest higher targets in settings where continuous pulse oximetry is not available but intermittent pulse oximetry is. We suggest a trial of awake prone positioning in patients who remain hypoxemic; however, this requires close monitoring, and clear failure and escalation criteria. In places with an adequate number and trained staff, the strategy seems safe. We recommend to intubate based on signs of respiratory distress more than on refractory hypoxemia alone, and we recommend close monitoring for respiratory worsening and early intubation if worsening occurs. We recommend low-tidal volume ventilation combined with FiO2 and positive end-expiratory pressure (PEEP) management based on a high FiO2/low PEEP table. We recommend against using routine recruitment maneuvers, unless as a rescue therapy in refractory hypoxemia, and we recommend using prone positioning for 12-16 hours in case of refractory hypoxemia (PaO2/FiO2 < 150 mmHg, FiO2 ≥ 0.6 and PEEP ≥ 10 cmH2O) in intubated patients as standard in ARDS patients. We also recommend against sharing one ventilator for multiple patients. We recommend daily assessments for readiness for weaning by a low-level pressure support and recommend against using a T-piece trial because of aerosolization risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.20-0796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957237PMC
January 2021

Pragmatic Recommendations for Tracheostomy, Discharge, and Rehabilitation Measures in Hospitalized Patients Recovering From Severe COVID-19 in Low- and Middle-Income Countries.

Am J Trop Med Hyg 2021 Jan 13. Epub 2021 Jan 13.

7Division of Pulmonary and Critical Care Medicine, Atrium Health, Charlotte, North Carolina.

New studies of COVID-19 are constantly updating best practices in clinical care. However, research mainly originates in resource-rich settings in high-income countries. Often, it is impractical to apply recommendations based on these investigations to resource-constrained settings in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for tracheostomy, discharge, and rehabilitation measures in hospitalized patients recovering from severe COVID-19 in LMICs. We recommend that tracheostomy be performed in a negative pressure room or negative pressure operating room, if possible, and otherwise in a single room with a closed door. We recommend using the technique that is most familiar to the institution and that can be conducted most safely. We recommend using fit-tested enhanced personal protection equipment, with the fewest people required, and incorporating strategies to minimize aerosolization of the virus. For recovering patients, we suggest following local, regional, or national hospital discharge guidelines. If these are lacking, we suggest deisolation and hospital discharge using symptom-based criteria, rather than with testing. We likewise suggest taking into consideration the capability of primary caregivers to provide the necessary care to meet the psychological, physical, and neurocognitive needs of the patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.20-1173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957235PMC
January 2021

Pragmatic Recommendations for the Use of Diagnostic Testing and Prognostic Models in Hospitalized Patients with Severe COVID-19 in Low- and Middle-Income Countries.

Am J Trop Med Hyg 2021 Jan 22. Epub 2021 Jan 22.

10Division of Pulmonary and Critical Care Medicine, Atrium Health, Charlotte, North Carolina.

Management of patients with severe or critical COVID-19 is mainly modeled after care of patients with severe pneumonia or acute respiratory distress syndrome from other causes. These models are based on evidence that primarily originates from investigations in high-income countries, but it may be impractical to apply these recommendations to resource-restricted settings in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for microbiology and laboratory testing, imaging, and the use of diagnostic and prognostic models in patients with severe COVID-19 in LMICs. For diagnostic testing, where reverse transcription-PCR (RT-PCR) testing is available and affordable, we recommend using RT-PCR of the upper or lower respiratory specimens and suggest using lower respiratory samples for patients suspected of having COVID-19 but have negative RT-PCR results for upper respiratory tract samples. We recommend that a positive RT-PCR from any anatomical source be considered confirmatory for SARS-CoV-2 infection, but, because false-negative testing can occur, recommend that a negative RT-PCR does not definitively rule out active infection if the patient has high suspicion for COVID-19. We suggest against using serologic assays for the detection of active or past SARS-CoV-2 infection, until there is better evidence for its usefulness. Where available, we recommend the use of point-of-care antigen-detecting rapid diagnostic testing for SARS-CoV-2 infection as an alternative to RT-PCR, only if strict quality control measures are guaranteed. For laboratory testing, we recommend a baseline white blood cell differential platelet count and hemoglobin, creatinine, and liver function tests and suggest a baseline C-reactive protein, lactate dehydrogenase, troponin, prothrombin time (or other coagulation test), and D-dimer, where such testing capabilities are available. For imaging, where availability of standard thoracic imaging is limited, we suggest using lung ultrasound to identify patients with possible COVID-19, but recommend against its use to exclude COVID-19. We suggest using lung ultrasound in combination with clinical parameters to monitor progress of the disease and responses to therapy in COVID-19 patients. We currently suggest against using diagnostic and prognostic models as these models require extensive laboratory testing and imaging, which often are limited in LMICs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4269/ajtmh.20-0730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957242PMC
January 2021

Systematic review of diagnostic methods for acute respiratory distress syndrome.

ERJ Open Res 2021 Jan 18;7(1). Epub 2021 Jan 18.

Dept of Intensive Care, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands.

Rationale: Acute respiratory distress syndrome (ARDS) is currently diagnosed by the Berlin definition, which does not include a direct measure of pulmonary oedema, endothelial permeability or pulmonary inflammation. We hypothesised that biomarkers of these processes have good diagnostic accuracy for ARDS.

Methods: Medline and Scopus were searched for original diagnostic studies using minimally invasive testing. Primary outcome was the diagnostic accuracy per test and was categorised by control group. The methodological quality was assessed with QUADAS-2 tool. Biomarkers that had an area under the receiver operating characteristic curve (AUROCC) of >0.75 and were studied with minimal bias against an unselected control group were considered to be promising.

Results: Forty-four articles were included. The median AUROCC for all evaluated tests was 0.80 (25th to 75th percentile: 0.72-0.88). The type of control group influenced the diagnostic accuracy (p=0.0095). Higher risk of bias was associated with higher diagnostic accuracy (AUROCC 0.75 for low-bias, 0.77 for intermediate-bias and 0.84 for high-bias studies; p=0.0023). Club cell protein 16 and soluble receptor for advanced glycation end-products in plasma and two panels with biomarkers of oxidative stress in breath showed good diagnostic accuracy in low-bias studies that compared ARDS patients to an unselected intensive care unit (ICU) population.

Conclusion: This systematic review revealed only four diagnostic tests fulfilling stringent criteria for a promising biomarker in a low-bias setting. For implementation into the clinical setting, prospective studies in a general unselected ICU population with good methodological quality are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00504-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836439PMC
January 2021

Instrumental dead space in ventilator management - Authors' reply.

Lancet Respir Med 2021 03 29;9(3):e23. Epub 2021 Jan 29.

Department of Intensive Care, Amsterdam University Medical Center, location Academic Medical Center, 1105 AZ Amsterdam, Netherlands; Department of Critical Care Medicine, Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(21)00015-1DOI Listing
March 2021

Nebulised heparin for patients on ventilation: implications for COVID-19 pneumonia.

Lancet Respir Med 2021 04 22;9(4):321-322. Epub 2021 Jan 22.

Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy; Anesthesia and Intensive Care, Ospedale Policlinico San Martino, IRCCS per l'Oncologia e le Neuroscienze, Genoa, Italy. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(20)30513-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826131PMC
April 2021

Consumptive coagulopathy is associated with a disturbed host response in patients with sepsis.

J Thromb Haemost 2021 04 17;19(4):1049-1063. Epub 2021 Feb 17.

Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Background: A prolonged prothrombin time (PT) is a common feature in sepsis indicating consumptive coagulopathy.

Objectives: To determine the association between a prolonged PT and aberrations in other host response mechanisms in sepsis.

Methods: Patients admitted to the intensive care unit with sepsis were divided in quartiles according to the highest PT value measured within 24 h after admission. The host response was evaluated by measuring 19 plasma biomarkers reflecting pathways implicated in sepsis pathogenesis and by blood leukocyte gene expression profiling.

Measurements And Main Results: Of 1524 admissions for sepsis, 386 (25.3%) involved patients with a normal PT (≤12.7 s); the remaining quartiles entailed 379 (24.9%) patients with a slightly prolonged PT (12.8 ≤ PT ≤ 15.0 s), 383 (25.1%) with an intermediately prolonged PT (15.1 ≤ PT ≤ 17.2 s), and 376 (24.7%) with an extremely prolonged PT (≥17.3 s). While patients with an extremely prolonged PT showed an increased crude mortality up to 1 year after admission, none of the prolonged PT groups was independently associated with 30-day adjusted mortality. Comparison of the host response between patients with a normal PT or an extremely prolonged PT matched for baseline characteristics including severity of disease showed that an extremely prolonged PT was associated with impaired anticoagulant mechanisms, a more disturbed endothelial barrier integrity and increased systemic inflammation, and blood leukocyte transcriptomes indicating more prominent metabolic reprogramming and protein catabolism.

Conclusion: A prolonged PT is associated with stronger anomalies in pathways implicated in the pathogenesis of sepsis, suggesting that activation of coagulation impacts other host response mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048632PMC
April 2021

Biological Subphenotypes of ARDS Show Prognostic Enrichment in Mechanically Ventilated Patients Without ARDS.

Am J Respir Crit Care Med 2021 Jan 19. Epub 2021 Jan 19.

Amsterdam UMC Location AMC, 26066, Department of Intensive Care Medicine, Amsterdam, Netherlands.

Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment.

Objectives: To determine whether these subphenotypes and their prognostic- and potential for predictive enrichment could be extended to other ICU patients, irrespective of fulfilling the definition of ARDS.

Methods: This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latent-class analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-, 30-day mortality and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and presence of ARDS.

Measurements And Main Results: We included 2499 mechanically ventilated patients (674 with and 1825 without ARDS). The cluster-derived "reactive" subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, a higher 30-day mortality, and a lower probability of successful extubation while alive compared to the "uninflamed" subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles.

Conclusion: The prognostic- and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202006-2522OCDOI Listing
January 2021