Publications by authors named "Mitchell M Levy"

170 Publications

BMI and pneumonia outcomes in critically ill COVID-19 patients: an international multicenter study.

Obesity (Silver Spring) 2021 May 9. Epub 2021 May 9.

Intensive Care Unit, Centre hospitalier de Dunkerque, 59240, Dunkerque.

Background: Previous studies unveiled a relation between the severity of COVID-19 pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, current smoking) in critically ill patients with COVID-19.

Methods: This multicenter retrospective cohort study enrolled patients admitted in intensive care for COVID-19, in 21 centers (Europe, Israel, USA) between 02/19/2020 and 05/19/2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV), and 28-day mortality.

Results: A total of 1,461 patients were enrolled, median(IQR) age was 64 years (40.9-72.0); 73.2% males; BMI 28.1 kg/m (25.4-32.3); 1,080 patients (73.9%) required IMV; the 28-day mortality estimate was 36.1% (95%CI, 33.0-39.5). Adjusted mixed logistic regression model showed a significant linear relation between BMI and IMV: OR 1.27 (95%CI, 1.12-1.45) per 5 kg/m . Adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was only increased in obesity class III (≥40 kg/m ) (HR 1.68 (95%CI 1.06-2.64).

Conclusion: In critically ill COVID-19 patients, we observed a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a non-linear association between BMI and mortality risk. (NCT04391738).
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http://dx.doi.org/10.1002/oby.23223DOI Listing
May 2021

Differences in Family Involvement in the Bedside Care of Patients in the ICU Based on Self-Identified Race.

Crit Care Explor 2021 Mar 15;3(3):e0365. Epub 2021 Mar 15.

Department of Medicine, Division of Pulmonary Sciences & Critical Care, University of Colorado Denver, Denver, CO.

Objectives: Being a caregiver for a patient in the ICU can place emotional burden on families and engaging families in caregiving can reduce psychological distress. Our goal was to observe support methods used by families in the ICU and identify differences between race/ethnicity.

Design: A secondary analysis of a multicenter before-and-after clinical trial.

Setting: Three hospitals in Chicago, Providence, and Florence, Italy.

Participants: Family members of patients admitted to the ICU.

Interventions: In the primary study, an intervention was designed to engage families in seven domains that were based on the five physical senses (taste, touch, sight, smell, and sound), personal care, and spiritual care of the patient. During the control phase, nursing staff observed and recorded if they witnessed families participating in support methods unprompted.

Measurements And Main Results: We compared the use of support methods among families from different races, categorized by race as either White, Black, or other using generalized estimating equation population-averaged logistic regression analysis. A total of 133 patients and 226 family members were enrolled in the control arm of the primary study, with patients being 71.2% White, 17% Black, and 11.8% other. Compared with Whites, families who identified their race Black or other may be more likely to participate in support methods that included personal care, touch, or spiritual care. Families who identified as Black may also be more likely to incorporate audio or sound. There were no differences in the categories of sight, smell, or taste.

Conclusions: Our study identifies racial differences in the use of bedside support methods in the ICU. Guiding families in a culturally congruent and open-minded manner may have the potential to decrease family distress and improve the experience for families in the ICU.
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http://dx.doi.org/10.1097/CCE.0000000000000365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994041PMC
March 2021

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

Crit Care Med 2021 03;49(3):e219-e234

Warren Alpert School of Medicine at Brown University, Providence, RI.

Background: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.

Methods: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility.

Results: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning.

Conclusion: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
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http://dx.doi.org/10.1097/CCM.0000000000004899DOI Listing
March 2021

Deep RNA Sequencing of Intensive Care Unit Patients with COVID-19.

medRxiv 2021 Jan 13. Epub 2021 Jan 13.

Purpose: COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19.

Methods: Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (>100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected.

Results: We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients.

Conclusions: Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies.

Take Home Message: Deep RNA sequencing provides a novel diagnostic tool for critically ill patients. Among ICU patients with COVID-19, RNA sequencings can identify gene expression, pathogens (including SARS-CoV-2), and can predict mortality.

Tweet: Deep RNA sequencing is a novel technology that can assist in the care of critically ill COVID-19 patients & can be applied to other disease.
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http://dx.doi.org/10.1101/2021.01.11.21249276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814849PMC
January 2021

The authors reply.

Crit Care Med 2020 Dec;48(12):e1371-e1372

Veterans Affairs Medical Center, Infectious Diseases Research Program and Center of Innovation in Long Term Services and Supports, Providence, RI, and College of Pharmacy, University of Rhode Island, Kingston, RI, and Division of Infectious Disease, Department of Internal Medicine, Warren Alpert Medical School of Brown University, Providence, RI.

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http://dx.doi.org/10.1097/CCM.0000000000004681DOI Listing
December 2020

Correlation Between Restraint Use and Engaging Family Members in the Care of ICU Patients.

Crit Care Explor 2020 Nov 5;2(11):e0255. Epub 2020 Nov 5.

Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, CO, and Department of Veterans Affairs, Eastern Colorado Health Care System, Denver, CO.

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http://dx.doi.org/10.1097/CCE.0000000000000255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655088PMC
November 2020

Survival From Severe Coronavirus Disease 2019: Is It Changing?

Crit Care Med 2021 02;49(2):351-353

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Alpert Medical School at Brown University, Providence, RI.

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http://dx.doi.org/10.1097/CCM.0000000000004753DOI Listing
February 2021

Increasing Quality, Not Costs.

Authors:
Mitchell M Levy

Crit Care Med 2020 10;48(10):1528-1529

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Warren Alpert School of Medicine at Brown University; and Medical Intensive Care Unit, Rhode Island Hospital, Providence, RI.

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http://dx.doi.org/10.1097/CCM.0000000000004527DOI Listing
October 2020

The authors reply.

Crit Care Med 2020 09;48(9):e841-e842

Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Brown University, Providence, RI.

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http://dx.doi.org/10.1097/CCM.0000000000004465DOI Listing
September 2020

Change in Carotid Blood Flow and Carotid Corrected Flow Time Assessed by Novice Sonologists Fails to Determine Fluid Responsiveness in Spontaneously Breathing Intensive Care Unit Patients.

Ultrasound Med Biol 2020 Oct 31;46(10):2659-2666. Epub 2020 Jul 31.

Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island, USA.

Measurement of carotid blood flow (CBF) and corrected carotid flow time (ccFT) has been proposed as a non-invasive means of determining fluid responsiveness. We evaluated the ability of CBF and ccFT as assessed by novice sonologists to determine fluid responsiveness in intensive care unit patients. Three novice physician sonologists performed carotid ultrasounds before and after a fluid bolus and calculated changes in CBF and ccFT. Fluid responsiveness was defined as a ≥10% increase in cardiac index as measured using bioreactance. Of 112 participants, 56 (50%) were fluid responders. Changes in CBF and ccFT performed poorly at determining fluid responsiveness: 19 mL/min (area under the receiver operating characteristic curve: 0.58, 95% confidence interval: 0.47-0.68) and 6 ms (0.59, 0.46-0.65) respectively. Novice physician sonologists are unable to determine fluid responsiveness using CBF or ccFT. Further research is needed to identify the key limiting factors in using carotid ultrasound to determine fluid responsiveness.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771259PMC
October 2020

Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response in Both Human and Mouse Endothelial Cells Induced Into a Sepsis Phenotype.

Crit Care Explor 2020 Jun 10;2(6):e0126. Epub 2020 Jun 10.

Department of Emergency Medicine, Warren Alpert School of Medicine, Brown University, Providence, RI.

Objectives: Sepsis is a leading cause of death in the United States. Putative targets to prevent systemic inflammatory response syndrome include antagonism of toll-like receptors 2 and 4 and CD44 receptors in vascular endothelial cells. Proteoglycan-4 is a mucinous glycoprotein that interacts with CD44 and toll-like receptor 4 resulting in a blockade of the NOD-like receptor pyrin domain-containing-3 pathway. We hypothesized that endothelial cells induced into a sepsis phenotype would have less interleukin-6 expression after recombinant human proteoglycan 4 treatment in vitro.

Design: Enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction to measure interleukin-6 protein and gene expression.

Setting: Research laboratory.

Subjects: Human umbilical vascular endothelial cells, human lung microvascular endothelial cells, and transgenic mouse (wild type) (/), (), (), and double knockout () lung microvascular endothelial cells.

Interventions: Cells were treated with 100 or 250 ng/mL lipopolysaccharide- K12 and subsequently treated with recombinant human proteoglycan 4 after 30 minutes. Interleukin-6 levels in conditioned media were measured via enzyme-linked immunosorbent assay and gene expression was measured via reverse transcriptase-quantitative polymerase chain reaction with ΔΔ-Ct analysis. Additionally, human umbilical vascular endothelial cells and human lung microvascular endothelial cells were treated with 1:10 diluted plasma from 15 patients with sepsis in culture media. After 30 minutes, either 50 or 100 µg/mL recombinant human proteoglycan 4 was administered. Interleukin-6 protein and gene expression were assayed. Proteoglycan 4 levels were also compared between control and sepsis patient plasma.

Measurements And Main Results: Human umbilical vascular endothelial cell, human lung microvascular endothelial cell, and mouse lung microvascular endothelial cell treated with lipopolysaccharide had significantly increased interleukin-6 protein compared with controls. Recombinant human proteoglycan-4 significantly reduced interleukin-6 in human and mouse endothelial cells. Interleukin-6 gene expression was significantly increased after lipopolysaccharide treatment compared with controls. This response was reversed by 50 or 100 µg/mL recombinant human proteoglycan-4 in 80% of sepsis samples in human umbilical vascular endothelial cells and in 60-73% in human lung microvascular endothelial cells. In genotypes of the mouse lung microvascular endothelial cells, recombinant human proteoglycan-4 significantly reduced interleukin-6 protein levels after lipopolysaccharide treatment, indicating that is not needed for recombinant human proteoglycan-4 to have an effect in a toll-like receptor 4 agonist inflammation model. Patient sepsis samples had higher plasma levels of native proteoglycan-4 than controls.

Interpretation And Conclusions: Recombinant human proteoglycan-4 is a potential adjunct therapy for sepsis patients and warrants future in vivo model studies.
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http://dx.doi.org/10.1097/CCE.0000000000000126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314356PMC
June 2020

Respiratory Variation in Carotid Artery Peak Systolic Velocity Is Unable to Predict Fluid Responsiveness in Spontaneously Breathing Critically Ill Patients When Assessed by Novice Physician Sonologists.

J Intensive Care Med 2020 Jun 29:885066620934392. Epub 2020 Jun 29.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, , Warren Alpert School of Medicine at Brown University, Providence, RI, USA.

Background: Respiratory variation in carotid artery peak systolic velocity (ΔVpeak) assessed by point-of-care ultrasound (POCUS) has been proposed as a noninvasive means to predict fluid responsiveness. We aimed to evaluate the ability of carotid ΔVpeak as assessed by novice physician sonologists to predict fluid responsiveness.

Methods: This study was conducted in 2 intensive care units. Spontaneously breathing, nonintubated patients with signs of volume depletion were included. Patients with atrial fibrillation/flutter, cardiogenic, obstructive or neurogenic shock, or those for whom further intravenous (IV) fluid administration would be harmful were excluded. Three novice physician sonologists were trained in POCUS assessment of carotid ΔVpeak. They assessed the carotid ΔVpeak in study participants prior to the administration of a 500 mL IV fluid bolus. Fluid responsiveness was defined as a ≥10% increase in cardiac index as measured using bioreactance.

Results: Eighty-six participants were enrolled, 50 (58.1%) were fluid responders. Carotid ΔVpeak performed poorly at predicting fluid responsiveness. Test characteristics for the optimum carotid ΔVpeak of 8.0% were: area under the receiver operating curve = 0.61 (95% CI: 0.48-0.73), sensitivity = 72.0% (95% CI: 58.3-82.56), specificity = 50.0% (95% CI: 34.5-65.5).

Conclusions: Novice physician sonologists using POCUS are unable to predict fluid responsiveness using carotid ΔVpeak. Until further research identifies key limiting factors, clinicians should use caution directing IV fluid resuscitation using carotid ΔVpeak.
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http://dx.doi.org/10.1177/0885066620934392DOI Listing
June 2020

Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial.

Chest 2020 10 27;158(4):1431-1445. Epub 2020 Apr 27.

Cheetah Medical, Wilmington, DE; Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA.

Background: Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome.

Research Question: Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?

Study Design And Methods: We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first.

Results: In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs 2.02 ± 3.44 L usual care arm; P = .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P = .04) or mechanical ventilation (17.7% vs 34.1%; P = .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals.

Interpretation: Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care.

Clinical Trial Registration: NCT02837731.
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http://dx.doi.org/10.1016/j.chest.2020.04.025DOI Listing
October 2020

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

Crit Care Med 2020 06;48(6):e440-e469

Department of Medicine and Surgery, Milano-Bicocca University, Milano, Italy.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.

Methods: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.

Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy.

Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.
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http://dx.doi.org/10.1097/CCM.0000000000004363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176264PMC
June 2020

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19).

Intensive Care Med 2020 05 28;46(5):854-887. Epub 2020 Mar 28.

Department of Medicine and Surgery, Milano-Bicocca University, Milan, Italy.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.

Methods: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.

Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.

Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.
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http://dx.doi.org/10.1007/s00134-020-06022-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866PMC
May 2020

Delay in Antibiotic Administration Is Associated With Mortality Among Septic Shock Patients With Staphylococcus aureus Bacteremia.

Crit Care Med 2020 04;48(4):525-532

Veterans Affairs Medical Center, Infectious Diseases Research Program and Center of Innovation in Long Term Services and Supports, Providence, RI.

Objectives: The relationship between the timing of antibiotics and mortality among septic shock patients has not been examined among patients specifically with Staphylococcus aureus bacteremia.

Design: Retrospective analysis of a Veterans Affairs S. aureus bacteremia database.

Setting: One-hundred twenty-two hospitals in the Veterans Affairs Health System.

Patients: Patients with septic shock and S. aureus bacteremia admitted directly from the emergency department to the ICU from January 1, 2003, to October 1, 2015, were evaluated.

Interventions: Time to appropriate antibiotic administration and 30-day mortality.

Measurements And Main Results: A total of 506 patients with S. aureus bacteremia and septic shock were included in the analysis. Thirty-day mortality was 78.1% for the entire cohort and was similar for those participants with methicillin-resistant S. aureus and methicillin-sensitive S. aureus bacteremia. Our multivariate analysis revealed that, as compared with those who received appropriate antibiotics within 1 hour after emergency department presentation, each additional hour that passed before appropriate antibiotics were administered produced an odds ratio of 1.11 (95% CI, 1.02-1.21) of mortality within 30 days. This odds increase equates to an average adjusted mortality increase of 1.3% (95% CI, 0.4-2.2%) for every hour that passes before antibiotics are administered.

Conclusions: The results of this study further support the importance of prompt appropriate antibiotic administration for patients with septic shock. Physicians should consider acting quickly to administer antibiotics with S. aureus coverage to any patient suspected of having septic shock.
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http://dx.doi.org/10.1097/CCM.0000000000004212DOI Listing
April 2020

Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis.

BMC Anesthesiol 2020 03 9;20(1):63. Epub 2020 Mar 9.

Section of Anesthesiology, Intensive Care and Pain Therapy, Departmnt of Health Sciences, University of Florence, Florence, Italy.

Background: The "END-of-Life ScorING-System" (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients.

Materials And Methods: Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient's ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis.

Results: Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort.

Conclusions: ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care.

Trial Registration: Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.
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http://dx.doi.org/10.1186/s12871-020-00979-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068991PMC
March 2020

Effect of Dexmedetomidine on duration of mechanical ventilation in septic patients: a systematic review and meta-analysis.

BMC Pulm Med 2020 Feb 17;20(1):42. Epub 2020 Feb 17.

Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Because of its analgesic and light sedative properties, the highly selective alpha-2 adrenergic receptor agonist dexmedetomidine (DEX) has been suggested for the treatment of septic patients, but its effect on the duration of mechanical ventilation remains unclear. The present study was conducted to review the extant literature in DEX and determine its influence on ventilation time in adult septic patients.

Methods: Databases of PubMed, Cochrane, and EMBASE were applied till 20th January 2019 without language restriction. The searching strategy as following: sepsis OR septic AND mechanical ventilation AND dexmedetomidine. Two authors screened titles, abstracts, and even articles to meet the including criterion independently. In addition, references of related articles or reviews were also referred. Data was recorded in a table and analyzed using the software of Review Manager 5.0.

Results: Four studies with a total of 349 patients were included. Three trials with 267 patients revealed the effect of DEX on duration of mechanical ventilation, two trials with 264 patients on ventilator-free days and four trials with 334 patients on 28-day mortality. The analyzed results indicated that DEX was not associated with significantly different durations of mechanical ventilation (MD 0.65, 95% CI, - 0.13 to 1.42, P = 0.10). However, there were significant differences in ventilator-free days (MD 3.57, 95% CI, 0.26 to 6.89, P = 0.03) and 28-day mortality (RR 0.61, 95% CI, 0.49 to 0.94, P = 0.02) in the septic patients.

Conclusion: Administration of DEX for sedation in septic patients was not associated with the duration of mechanical ventilation, but it increased the ventilator-free days and reduced 28-day mortality.
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http://dx.doi.org/10.1186/s12890-020-1065-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026965PMC
February 2020

Identifying the Burden of Sepsis With Big Data.

Authors:
Mitchell M Levy

Crit Care Med 2020 03;48(3):422-423

Division of Pulmonary, Critical Care and Sleep Medicine, Warren Alpert School of Medicine at Brown University; and Medical Intensive Care Unit, Rhode Island Hospital, Providence, RI.

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http://dx.doi.org/10.1097/CCM.0000000000004229DOI Listing
March 2020

Effect of Best Practice Advisories on Sedation Protocol Compliance and Drug-Related Hazardous Condition Mitigation Among Critical Care Patients.

Crit Care Med 2020 02;48(2):185-191

Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI.

Objectives: To determine whether best practice advisories improved sedation protocol compliance and could mitigate potential propofol-related hazardous conditions.

Design: Retrospective observational cohort study.

Setting: Two adult ICUs at two academic medical centers that share the same sedation protocol.

Patients: Adults 18 years old or older admitted to the ICU between January 1, 2016, and January 31, 2018, who received a continuous infusion of propofol.

Interventions: Two concurrent best practice advisories built in the electronic health record as a clinical decision support tool to enforce protocol compliance with triglyceride and lipase level monitoring and mitigate propofol-related hazardous conditions.

Measurements And Main Results: The primary outcomes were baseline and day 3 compliance with triglyceride and lipase laboratory monitoring per protocol and time to discontinuation of propofol in the setting of triglyceride and/or lipase levels exceeding protocol cutoffs. A total of 1,394 patients were included in the study cohort (n = 700 in the pre-best practice advisory group; n = 694 in the post-best practice advisory group). In inverse probability weighted regression analyses, implementing the best practice advisory was associated with a 56.6% (95% CI, 52.6-60.9) absolute increase and a 173% relative increase (risk ratio, 2.73; 95% CI, 2.45-3.04) in baseline laboratory monitoring. The best practice advisory was associated with a 34.0% (95% CI, 20.9-47.1) absolute increase and a 74% (95% CI, 1.39-2.19) relative increase in day 3 laboratory monitoring after inverse probability weighted analyses. Among patients with laboratory values exceeding protocol cutoffs, implementation of the best practice advisory resulted in providers discontinuing propofol an average of 16.6 hours (95% CI, 4.8-28.3) sooner than pre-best practice advisory. Findings from alternate analyses using interrupted time series were consistent with the inverse probability weighted analyses.

Conclusions: Best practice advisories can be effectively used in ICUs to improve sedation protocol compliance and may mitigate potential propofol-related hazardous conditions. Best practice advisories should undergo continuous quality assurance and optimizations to maximize clinical utility and minimize alert fatigue.
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http://dx.doi.org/10.1097/CCM.0000000000004116DOI Listing
February 2020

Family Care Rituals in the ICU to Reduce Symptoms of Post-Traumatic Stress Disorder in Family Members-A Multicenter, Multinational, Before-and-After Intervention Trial.

Crit Care Med 2020 02;48(2):176-184

Department of Medicine, Division of Pulmonary, Critical Care & Sleep, Brown University, Providence, RI.

Objectives: To assess the feasibility and efficacy of implementing "Family Care Rituals" as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members.

Design: Prospective, before-and-after intervention evaluation.

Setting: Two U.S. academic medical ICU's, and one Italian academic medical/surgical ICU.

Subjects: Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission.

Interventions: A novel intervention titled "Family Care Rituals" during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay.

Measurements And Main Results: Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction. At 90-day follow-up, 131 of 226 family members (58.0%) responded preintervention and 129 of 226 family members (57.1%) responded postintervention. Symptoms of post-traumatic stress disorder were significantly higher preintervention than postintervention (39.2% vs 27.1%; unadjusted odds ratio, 0.58; p = 0.046). There was no significant difference in symptoms of depression (26.5% vs 25.2%; unadjusted odds ratio, 0.93; p = 0.818), anxiety (41.0% vs 45.5%; unadjusted odds ratio, 1.20; p = 0.234), or mean satisfaction scores (85.1 vs 89.0; unadjusted odds ratio, 3.85; p = 0.052) preintervention versus postintervention 90 days after patient death or ICU discharge.

Conclusions: Offering opportunities such as family care rituals for family members to be involved with providing care for family members in the ICU was associated with reduced symptoms of post-traumatic stress disorder. This intervention may lessen the burden of stress-related symptoms in family members of ICU patients.
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http://dx.doi.org/10.1097/CCM.0000000000004113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147959PMC
February 2020

Fluctuations of consciousness after stroke: Associations with the confusion assessment method for the intensive care unit (CAM-ICU) and potential undetected delirium.

J Crit Care 2020 04 10;56:58-62. Epub 2019 Dec 10.

Department of Neurology, Brown University, Alpert Medical School, United States of America; Department of Psychiatry and Human Behavior, Brown University, Alpert Medical School, United States of America.

Purpose: To examine associations between fluctuating consciousness and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) assessments in stroke patients compared to non-neurological patients.

Materials And Methods: We linked all recorded CAM-ICU assessments with corresponding Richmond Agitation Sedation Scale (RASS) measurements in patients with stroke or sepsis from a single-center ICU database. Fluctuating consciousness was defined by RASS variability using standard deviations (SD) over 24-h periods; regression analyses were performed to determine associations with RASS variability and CAM-ICU rating.

Results: We identified 16,509 paired daily summaries of CAM-ICU and RASS measurements in 546 stroke patients and 1586 sepsis patients. Stroke patients had higher odds of positive (OR 4.2, 95% CI 3.3-5.5) and "unable to assess" (UTA; OR 5.2, 95% CI 4.0-6.8) CAM-ICU ratings compared to sepsis patients, and CAM-ICU-positive and UTA assessment-days had higher RASS variability than CAM-ICU-negative assessment-days, especially in stroke patients. Based on model-implied associations of RASS variability (OR 2.0 per semi-IQR-difference in RASS-SD, 95% CI 1.7-2.2) and stroke diagnosis (OR 2.7, 95% CI 2.0-3.7) with CAM-ICU-positive assessments, over one-third of probable delirium cases among stroke patients were potentially missed by the CAM-ICU.

Conclusions: Post-stroke delirium may frequently go undetected by the CAM-ICU, even in the setting of fluctuating consciousness.
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http://dx.doi.org/10.1016/j.jcrc.2019.12.008DOI Listing
April 2020

Treatment of Patients with Severe Sepsis and Septic Shock: Current Evidence-Based Practices.

R I Med J (2013) 2019 Dec 2;102(10):18-21. Epub 2019 Dec 2.

Division of Pulmonary, Critical Care and Sleep Medicine, Warren Alpert Medical School of Brown University, Providence, RI.

Sepsis remains a field of active research with many unknown and unanswered questions. Over the past few decades, advancements in sepsis management have led to improved mortality and morbidity. This article will review the current evidence-based practices of the treatment of sepsis and septic shock. It will also critically appraise some of the current controversies in sepsis management, such as fluids, steroids, early vasopressors, early goal-directed therapy and immunotherapy.
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December 2019

The SOFA score-development, utility and challenges of accurate assessment in clinical trials.

Crit Care 2019 Nov 27;23(1):374. Epub 2019 Nov 27.

Intensive care unit & Inserm CIC 1435 & Inserm UMR 1092, Dupuytren University Hospital, Limoges, France.

The Sequential Organ Failure Assessment or SOFA score was developed to assess the acute morbidity of critical illness at a population level and has been widely validated as a tool for this purpose across a range of healthcare settings and environments.In recent years, the SOFA score has become extensively used in a range of other applications. A change in the SOFA score of 2 or more is now a defining characteristic of the sepsis syndrome, and the European Medicines Agency has accepted that a change in the SOFA score is an acceptable surrogate marker of efficacy in exploratory trials of novel therapeutic agents in sepsis. The requirement to detect modest serial changes in a patients' SOFA score therefore means that increased clarity on how the score should be assessed in different circumstances is required.This review explores the development of the SOFA score, its applications and the challenges associated with measurement. In addition, it proposes guidance designed to facilitate the consistent and valid assessment of the score in multicentre sepsis trials involving novel therapeutic agents or interventions.ConclusionThe SOFA score is an increasingly important tool in defining both the clinical condition of the individual patient and the response to therapies in the context of clinical trials. Standardisation between different assessors in widespread centres is key to detecting response to treatment if the SOFA score is to be used as an outcome in sepsis clinical trials.
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http://dx.doi.org/10.1186/s13054-019-2663-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880479PMC
November 2019

Preface.

Authors:
Mitchell M Levy

Crit Care Clin 2020 Jan;36(1):xiii-xiv

Division of Pulmonary, Critical Care and Sleep Medicine, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, 4th Floor Main Building, Providence, RI 02903, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ccc.2019.10.001DOI Listing
January 2020

Biomarkers of Immunosuppression.

Crit Care Clin 2020 Jan;36(1):167-176

Division of Pulmonary, Critical Care, and Sleep Medicine, Alpert Medical School of Brown University, Physicians Office Building, Suite 224, 110 Lockwood street, Providence, RI 02903, USA. Electronic address:

It is now recognized that sepsis is not a uniformly proinflammatory state. There is a well-recognized counter anti-inflammatory response that occurs in many patients. The timing and magnitude of this response varies considerably and thus makes its identification and manipulation more difficult. Studies in animals and humans have now identified a small number of biologic responses that characterize this immunosuppressed state, such as lymphocyte death, HLA receptor downregulation, and monocyte exhaustion. Researchers are now trying to use these as markers of individual immunosuppression to predict outcomes and identify patients who would and would not benefit from new immune stimulatory therapies.
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http://dx.doi.org/10.1016/j.ccc.2019.08.013DOI Listing
January 2020

Performance of a 25% Inferior Vena Cava Collapsibility in Detecting Fluid Responsiveness When Assessed by Novice Versus Expert Physician Sonologists.

J Intensive Care Med 2020 Dec 14;35(12):1520-1528. Epub 2019 Oct 14.

Department of Medicine, 12321Alert Medical School of Brown University, Providence, RI, USA.

Objectives: Inferior vena cava collapsibility (cIVC) measured by point-of-care ultrasound (POCUS) has been proposed as a noninvasive means of assessing fluid responsiveness. We aimed to prospectively evaluate the performance of a 25% cIVC cutoff value to detect fluid responsiveness among spontaneously breathing intensive care unit (ICU) patients when assessed with POCUS by novice versus expert physician sonologists.

Methods: Prospective observational study of spontaneously breathing ICU patients. Fluid responsiveness was defined as a 10% increase in cardiac index following a 500 mL fluid bolus, measured by bioreactance. Novice sonologist measured cIVC with POCUS. Their measurements were later compared to an expert physician sonologist who independently reviewed the POCUS images and assessed cIVCs.

Results: Of the 85 participants, 44 (52%) were fluid responders. A 25% cIVC cutoff value performed better when assessed by expert sonologists than novice physician sonologists (receiver-operator characteristic curve, ROC = 0.82 [0.74-0.88] vs ROC = 0.69 [0.60-0.77]).

Conclusions: A 25% cIVC cutoff value measured by POCUS detects fluid responsiveness. However, the experience of the physician sonologist affects test performance and should be considered when interpreting and clinically using cIVC to direct intravenous fluid resuscitation.
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http://dx.doi.org/10.1177/0885066619881123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153972PMC
December 2020

Implementation of Sepsis Bundles: Just Do It!!

Authors:
Mitchell M Levy

Crit Care Med 2019 10;47(10):1450-1451

Department of Medicine at the Division of Pulmonary, Critical Care and Sleep Medicine, Warren Alpert School of Medicine at Brown University, Providence, RI.

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http://dx.doi.org/10.1097/CCM.0000000000003941DOI Listing
October 2019

The Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock (RIFTS): A Randomized Pilot Study.

Crit Care Med 2019 07;47(7):951-959

Department of Medicine, Division of Pulmonary Critical Care and Sleep, Alpert Medical School of Brown University, Providence, RI.

Objectives: It is unclear if a low- or high-volume IV fluid resuscitation strategy is better for patients with severe sepsis and septic shock.

Design: Prospective randomized controlled trial.

Setting: Two adult acute care hospitals within a single academic system.

Patients: Patients with severe sepsis and septic shock admitted from the emergency department to the ICU from November 2016 to February 2018.

Interventions: Patients were randomly assigned to a restrictive IV fluid resuscitation strategy (≤ 60 mL/kg of IV fluid) or usual care for the first 72 hours of care.

Measurements And Main Results: We enrolled 109 patients, of whom 55 were assigned to the restrictive resuscitation group and 54 to the usual care group. The restrictive group received significantly less resuscitative IV fluid than the usual care group (47.1 vs 61.1 mL/kg; p = 0.01) over 72 hours. By 30 days, there were 12 deaths (21.8%) in the restrictive group and 12 deaths (22.2%) in the usual care group (odds ratio, 1.02; 95% CI, 0.41-2.53). There were no differences between groups in the rate of new organ failure, hospital or ICU length of stay, or serious adverse events.

Conclusions: This pilot study demonstrates that a restrictive resuscitation strategy can successfully reduce the amount of IV fluid administered to patients with severe sepsis and septic shock compared with usual care. Although limited by the sample size, we observed no increase in mortality, organ failure, or adverse events. These findings further support that a restrictive IV fluid strategy should be explored in a larger multicenter trial.
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http://dx.doi.org/10.1097/CCM.0000000000003779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579683PMC
July 2019