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Publication Record


Incidence and Outcomes of Acute Laryngeal Injury After Prolonged Mechanical Ventilation.
Shinn JR, Kimura KS, Campbell BR, Sun Lowery A, Wootten CT, Garrett CG, Francis DO, Hillel AT, Du L, Casey JD, Ely EW, Gelbard A
(2019) Crit Care Med 47: 1699-1706
MeSH Terms: Acute Disease, Adult, Aged, Female, Humans, Incidence, Intubation, Intratracheal, Larynx, Male, Middle Aged, Prospective Studies, Respiration Disorders, Respiration, Artificial, Time Factors, Voice Disorders, Wounds and Injuries
Show Abstract · Added July 30, 2020
OBJECTIVES - Upper airway injury is a recognized complication of prolonged endotracheal intubation, yet little attention has been paid to the consequences of laryngeal injury and functional impact. The purpose of our study was to prospectively define the incidence of acute laryngeal injury and investigate the impact of injury on breathing and voice outcomes.
DESIGN - Prospective cohort study.
SETTING - Tertiary referral critical care center.
PATIENTS - Consecutive adult patients intubated greater than 12 hours in the medical ICU from August 2017 to May 2018 who underwent laryngoscopy within 36 hours of extubation.
INTERVENTIONS - Laryngoscopy following endotracheal intubation.
MEASUREMENTS AND MAIN RESULTS - One hundred consecutive patients (62% male; median age, 58.5 yr) underwent endoscopic examination after extubation. Acute laryngeal injury (i.e., mucosal ulceration or granulation tissue in the larynx) was present in 57 patients (57%). Patients with laryngeal injury had significantly worse patient-reported breathing (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 1.05; interquartile range, 0.48-2.10) and vocal symptoms (Voice Handicap Index-10: median, 2; interquartile range, 0-6) compared with patients without injury (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 0.20; interquartile range, 0-0.80; p < 0.001; and Voice Handicap Index-10: median, 0; interquartile range, 0-1; p = 0.005). Multivariable logistic regression independently associated diabetes, body habitus, and endotracheal tube size greater than 7.0 with the development of laryngeal injury.
CONCLUSIONS - Acute laryngeal injury occurs in more than half of patients who receive mechanical ventilation and is associated with significantly worse breathing and voicing 10 weeks after extubation. An endotracheal tube greater than size 7.0, diabetes, and larger body habitus may predispose to injury. Our results suggest that acute laryngeal injury impacts functional recovery from critical illness.
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MeSH Terms
The Cost of ICU Delirium and Coma in the Intensive Care Unit Patient.
Vasilevskis EE, Chandrasekhar R, Holtze CH, Graves J, Speroff T, Girard TD, Patel MB, Hughes CG, Cao A, Pandharipande PP, Ely EW
(2018) Med Care 56: 890-897
MeSH Terms: Adult, Aged, Coma, Comorbidity, Costs and Cost Analysis, Critical Illness, Delirium, Dialysis, Female, Humans, Intensive Care Units, Male, Middle Aged, Prospective Studies, Respiration, Artificial, Risk Factors
Show Abstract · Added September 5, 2018
RATIONALE - Intensive care unit (ICU) delirium is highly prevalent and a potentially avoidable hospital complication. The current cost of ICU delirium is unknown.
OBJECTIVES - To specify the association between the daily occurrence of delirium in the ICU with costs of ICU care accounting for time-varying illness severity and death.
RESEARCH DESIGN - We performed a prospective cohort study within medical and surgical ICUs in a large academic medical center.
SUBJECTS - We analyzed critically ill patients (N=479) with respiratory failure and/or shock.
MEASURES - Covariates included baseline factors (age, insurance, cognitive impairment, comorbidities, Acute Physiology and Chronic Health Evaluation II Score) and time-varying factors (sequential organ failure assessment score, mechanical ventilation, and severe sepsis). The primary analysis used a novel 3-stage regression method: first, estimation of the cumulative cost of delirium over 30 ICU days and then costs separated into those attributable to increased resource utilization among survivors and those that were avoided on the account of delirium's association with early mortality in the ICU.
RESULTS - The patient-level 30-day cumulative cost of ICU delirium attributable to increased resource utilization was $17,838 (95% confidence interval, $11,132-$23,497). A combination of professional, dialysis, and bed costs accounted for the largest percentage of the incremental costs associated with ICU delirium. The 30-day cumulative incremental costs of ICU delirium that were avoided due to delirium-associated early mortality was $4654 (95% confidence interval, $2056-7869).
CONCLUSIONS - Delirium is associated with substantial costs after accounting for time-varying illness severity and could be 20% higher (∼$22,500) if not for its association with early ICU mortality.
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16 MeSH Terms
Sedative Plasma Concentrations and Delirium Risk in Critical Illness.
Stollings JL, Thompson JL, Ferrell BA, Scheinin M, Wilkinson GR, Hughes CG, Shintani AK, Ely EW, Girard TD, Pandharipande PP, Patel MB
(2018) Ann Pharmacother 52: 513-521
MeSH Terms: Aged, Critical Illness, Delirium, Dexmedetomidine, Female, Humans, Hypnotics and Sedatives, Intensive Care Units, Logistic Models, Lorazepam, Male, Middle Aged, Respiration, Artificial
Show Abstract · Added June 26, 2018
BACKGROUND - The relationship between plasma concentration of sedatives and delirium is unknown.
OBJECTIVE - We hypothesized that higher plasma concentrations of lorazepam are associated with increased delirium risk, whereas higher plasma concentrations of dexmedetomidine are associated with reduced delirium risk.
METHODS - This prospective cohort study was embedded in a double-blind randomized clinical trial, where ventilated patients received infusions of lorazepam and dexmedetomidine. Plasma concentrations of these drugs and delirium assessments were measured at least daily. A multivariable logistic regression model accounting for repeated measures was used to analyze associations between same-day plasma concentrations of lorazepam and dexmedetomidine (exposures) and the likelihood of next-day delirium (outcome), adjusting for same-day mental status (delirium, coma, or normal) and same-day fentanyl doses.
RESULTS - This critically ill cohort (n = 103) had a median age of 60 years (IQR: 48-66) with APACHE II score of 28 (interquartile range [IQR] = 24-32), where randomization resulted in assignment to lorazepam (n = 51) or dexmedetomidine (n = 52). After adjusting for same-day fentanyl dose and mental status, higher plasma concentrations of lorazepam were associated with increased probability of next-day delirium (comparing 500 vs 0 ng/mL; odds ratio [OR] = 13.2; 95% CI = 1.4-120.1; P = 0.02). Plasma concentrations of dexmedetomidine were not associated with next-day delirium (comparing 1 vs 0 ng/mL; OR = 1.1; 95% CI = 0.9-1.3; P = 0.45).
CONCLUSIONS - In critically ill patients, higher lorazepam plasma concentrations were associated with delirium, whereas dexmedetomidine plasma concentrations were not. This implies that the reduced delirium risk seen in patients sedated with dexmedetomidine may be a result of avoidance of benzodiazepines, rather than a dose-dependent protective effect of dexmedetomidine.
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13 MeSH Terms
Novel Method for Noninvasive Sampling of the Distal Airspace in Acute Respiratory Distress Syndrome.
McNeil JB, Shaver CM, Kerchberger VE, Russell DW, Grove BS, Warren MA, Wickersham NE, Ware LB, McDonald WH, Bastarache JA
(2018) Am J Respir Crit Care Med 197: 1027-1035
MeSH Terms: Aged, Diagnostic Techniques, Respiratory System, Female, Gelatin Sponge, Absorbable, Humans, Male, Middle Aged, Minimally Invasive Surgical Procedures, Pulmonary Alveoli, Respiration, Artificial, Respiratory Distress Syndrome, Adult
Show Abstract · Added May 31, 2018
RATIONALE - A major barrier to a more complete understanding of acute respiratory distress syndrome (ARDS) pathophysiology is the inability to sample the distal airspace of patients with ARDS. The heat moisture exchanger (HME) filter is an inline bacteriostatic sponge that collects exhaled moisture from the lungs of mechanically ventilated patients.
OBJECTIVES - To test the hypothesis that HME filter fluid (HMEF) represents the distal airspace fluid in patients with ARDS.
METHODS - Samples of HMEF were collected from 37 patients with acute pulmonary edema (either from ARDS or hydrostatic causes [HYDRO; control subjects]). Concurrent undiluted pulmonary edema fluid (EF) and HMEF were collected from six patients. HMEF from 11 patients (8 ARDS and 3 HYDRO) were analyzed by liquid chromatography-coupled tandem mass spectometry. Total protein (bicinchoninic acid assay), MMP-9 (matrix metalloproteinase-9), and MPO (myeloperoxidase) (ELISA) were measured in 29 subjects with ARDS and 5 subjects with HYDRO. SP-D (surfactant protein-D), RAGE (receptor for advanced glycation end-products) (ELISA), and cytokines (IL-1β, IL-6, IL-8, and tumor necrosis factor-α) (electrochemiluminescent assays) were measured in six concurrent HMEF and EF samples.
MEASUREMENTS AND MAIN RESULTS - Liquid chromatography-coupled tandem mass spectrometry on concurrent EF and HMEF samples from four patients revealed similar base peak intensities and m/z values indicating similar protein composition. There were 21 significantly elevated proteins in HMEF from patients with ARDS versus HYDRO. Eight proteins measured in concurrent EF and HMEF from six patients were highly correlated. In HMEF, total protein and MMP-9 were significantly higher in ARDS than in HYDRO.
CONCLUSIONS - These data suggest that HMEF is a novel, noninvasive method to accurately sample the distal airspace in patients with ARDS.
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11 MeSH Terms
Delirium and Catatonia in Critically Ill Patients: The Delirium and Catatonia Prospective Cohort Investigation.
Wilson JE, Carlson R, Duggan MC, Pandharipande P, Girard TD, Wang L, Thompson JL, Chandrasekhar R, Francis A, Nicolson SE, Dittus RS, Heckers S, Ely EW, Delirium and Catatonia (DeCat) Prospective Cohort Investigation
(2017) Crit Care Med 45: 1837-1844
MeSH Terms: Aged, Catatonia, Critical Illness, Delirium, Female, Humans, Intensive Care Units, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Respiration, Artificial, Severity of Illness Index, Vasoconstrictor Agents
Show Abstract · Added March 30, 2020
OBJECTIVES - Catatonia, a condition characterized by motor, behavioral, and emotional changes, can occur during critical illness and appear as clinically similar to delirium, yet its management differs from delirium. Traditional criteria for medical catatonia preclude its diagnosis in delirium. Our objective in this investigation was to understand the overlap and relationship between delirium and catatonia in ICU patients and determine diagnostic thresholds for catatonia.
DESIGN - Convenience cohort, nested within two ongoing randomized trials.
SETTING - Single academic medical center in Nashville, TN.
PATIENTS - We enrolled 136 critically ill patients on mechanical ventilation and/or vasopressors, randomized to two usual care sedation regimens.
MEASUREMENTS AND MAIN RESULTS - Patients were assessed for delirium and catatonia by independent and masked personnel using Confusion Assessment Method for the ICU and the Bush Francis Catatonia Rating Scale mapped to Diagnostic Statistical Manual 5 criterion A for catatonia. Of 136 patients, 58 patients (43%) had only delirium, four (3%) had only catatonia, 42 (31%) had both, and 32 (24%) had neither. In a logistic regression model, more catatonia signs were associated with greater odds of having delirium. For example, patient assessments with greater than or equal to three Diagnostic Statistical Manual 5 symptoms (75th percentile) had, on average, 27.8 times the odds (interquartile range, 12.7-60.6) of having delirium compared with patient assessments with zero Diagnostic Statistical Manual 5 criteria (25th percentile) present (p < 0.001). A cut-off of greater than or equal to 4 Bush Francis Catatonia Screening Instrument items was both sensitive (91%; 95% CI, 82.9-95.3) and specific (91%; 95% CI, 87.6-92.9) for Diagnostic Statistical Manual 5 catatonia.
CONCLUSIONS - Given that about one in three patients had both catatonia and delirium, these data prompt reconsideration of Diagnostic Statistical Manual 5 criteria for "Catatonic Disorder Due to Another Medical Condition" that preclude diagnosing catatonia in the presence of delirium.
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Community-Acquired Pneumonia Visualized on CT Scans but Not Chest Radiographs: Pathogens, Severity, and Clinical Outcomes.
Upchurch CP, Grijalva CG, Wunderink RG, Williams DJ, Waterer GW, Anderson EJ, Zhu Y, Hart EM, Carroll F, Bramley AM, Jain S, Edwards KM, Self WH
(2018) Chest 153: 601-610
MeSH Terms: Adult, Aged, Anti-Infective Agents, Community-Acquired Infections, Female, Hospital Mortality, Humans, Length of Stay, Male, Middle Aged, Pneumonia, Prospective Studies, Radiography, Thoracic, Respiration, Artificial, Severity of Illness Index, Tomography, X-Ray Computed, United States
Show Abstract · Added July 27, 2018
BACKGROUND - The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain.
METHODS - In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data.
RESULTS - The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%).
CONCLUSIONS - Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.
Copyright © 2017 American College of Chest Physicians. All rights reserved.
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17 MeSH Terms
Relationship Between Body Mass Index and Outcomes Among Hospitalized Patients With Community-Acquired Pneumonia.
Bramley AM, Reed C, Finelli L, Self WH, Ampofo K, Arnold SR, Williams DJ, Grijalva CG, Anderson EJ, Stockmann C, Trabue C, Fakhran S, Balk R, McCullers JA, Pavia AT, Edwards KM, Wunderink RG, Jain S, Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) Study Team
(2017) J Infect Dis 215: 1873-1882
MeSH Terms: Adolescent, Adult, Aged, Asthma, Body Mass Index, Child, Child, Preschool, Community-Acquired Infections, Comorbidity, Female, Hospitalization, Humans, Intensive Care Units, Length of Stay, Male, Middle Aged, Obesity, Odds Ratio, Pneumonia, Prospective Studies, Respiration, Artificial, Treatment Outcome, Young Adult
Show Abstract · Added July 27, 2018
Background - The effect of body mass index (BMI) on community-acquired pneumonia (CAP) severity is unclear.
Methods - We investigated the relationship between BMI and CAP outcomes (hospital length of stay [LOS], intensive care unit [ICU] admission, and invasive mechanical ventilation) in hospitalized CAP patients from the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, adjusting for age, demographics, underlying conditions, and smoking status (adults only).
Results - Compared with normal-weight children, odds of ICU admission were higher in children who were overweight (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.1-2.8) or obese (aOR, 2.1; 95% CI, 1.4-3.2), and odds of mechanical ventilation were higher in children with obesity (aOR, 2.7; 95% CI, 1.3-5.6). When stratified by asthma (presence/absence), these findings remained significant only in children with asthma. Compared with normal-weight adults, odds of LOS >3 days were higher in adults who were underweight (aOR, 1.6; 95% CI, 1.1-2.4), and odds of mechanical ventilation were lowest in adults who were overweight (aOR, 0.5; 95% CI, .3-.9).
Conclusions - Children who were overweight or obese, particularly those with asthma, had higher odds of ICU admission or mechanical ventilation. In contrast, adults who were underweight had longer LOS. These results underscore the complex relationship between BMI and CAP outcomes.
Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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Interdisciplinary Care of Children with Severe Bronchopulmonary Dysplasia.
Abman SH, Collaco JM, Shepherd EG, Keszler M, Cuevas-Guaman M, Welty SE, Truog WE, McGrath-Morrow SA, Moore PE, Rhein LM, Kirpalani H, Zhang H, Gratny LL, Lynch SK, Curtiss J, Stonestreet BS, McKinney RL, Dysart KC, Gien J, Baker CD, Donohue PK, Austin E, Fike C, Nelin LD, Bronchopulmonary Dysplasia Collaborative
(2017) J Pediatr 181: 12-28.e1
MeSH Terms: Bronchopulmonary Dysplasia, Humans, Infant Care, Infant, Newborn, Infant, Premature, Patient Care Team, Respiration, Artificial, Tracheostomy
Added February 21, 2017
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8 MeSH Terms
Predicting Severe Pneumonia Outcomes in Children.
Williams DJ, Zhu Y, Grijalva CG, Self WH, Harrell FE, Reed C, Stockmann C, Arnold SR, Ampofo KK, Anderson EJ, Bramley AM, Wunderink RG, McCullers JA, Pavia AT, Jain S, Edwards KM
(2016) Pediatrics 138:
MeSH Terms: Age Factors, Child, Preschool, Community-Acquired Infections, Female, Hospitalization, Humans, Infant, Intensive Care Units, Pediatric, Length of Stay, Lung, Male, Models, Statistical, Patient Admission, Patient Outcome Assessment, Pneumonia, Prognosis, Prospective Studies, Respiration, Artificial, Risk Assessment, Severity of Illness Index, Shock, United States, Vital Signs
Show Abstract · Added July 27, 2018
BACKGROUND - Substantial morbidity and excessive care variation are seen with pediatric pneumonia. Accurate risk-stratification tools to guide clinical decision-making are needed.
METHODS - We developed risk models to predict severe pneumonia outcomes in children (<18 years) by using data from the Etiology of Pneumonia in the Community Study, a prospective study of community-acquired pneumonia hospitalizations conducted in 3 US cities from January 2010 to June 2012. In-hospital outcomes were organized into an ordinal severity scale encompassing severe (mechanical ventilation, shock, or death), moderate (intensive care admission only), and mild (non-intensive care hospitalization) outcomes. Twenty predictors, including patient, laboratory, and radiographic characteristics at presentation, were evaluated in 3 models: a full model included all 20 predictors, a reduced model included 10 predictors based on expert consensus, and an electronic health record (EHR) model included 9 predictors typically available as structured data within comprehensive EHRs. Ordinal regression was used for model development. Predictive accuracy was estimated by using discrimination (concordance index).
RESULTS - Among the 2319 included children, 21% had a moderate or severe outcome (14% moderate, 7% severe). Each of the models accurately identified risk for moderate or severe pneumonia (concordance index across models 0.78-0.81). Age, vital signs, chest indrawing, and radiologic infiltrate pattern were the strongest predictors of severity. The reduced and EHR models retained most of the strongest predictors and performed as well as the full model.
CONCLUSIONS - We created 3 risk models that accurately estimate risk for severe pneumonia in children. Their use holds the potential to improve care and outcomes.
Copyright © 2016 by the American Academy of Pediatrics.
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Randomized Trial of Video Laryngoscopy for Endotracheal Intubation of Critically Ill Adults.
Janz DR, Semler MW, Lentz RJ, Matthews DT, Assad TR, Norman BC, Keriwala RD, Ferrell BA, Noto MJ, Shaver CM, Richmond BW, Zinggeler Berg J, Rice TW, Facilitating EndotracheaL intubation by Laryngoscopy technique and apneic Oxygenation Within the ICU Investigators and the Pragmatic Critical Care Research Group
(2016) Crit Care Med 44: 1980-1987
MeSH Terms: Academic Medical Centers, Aged, Carbon Dioxide, Critical Illness, Female, Hospital Mortality, Humans, Intensive Care Units, Intubation, Intratracheal, Laryngoscopy, Length of Stay, Male, Middle Aged, Oxygen, Prospective Studies, Respiration, Artificial, Time Factors, Video Recording
Show Abstract · Added March 30, 2020
OBJECTIVE - To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults.
DESIGN - A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows.
SETTING - Medical ICU in a tertiary, academic medical center.
PATIENTS - Critically ill patients 18 years old or older.
INTERVENTIONS - Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation.
MEASUREMENTS AND MAIN RESULTS - Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% vs direct 65.8%; p = 0.68) in unadjusted analyses or after adjustment for the operator's previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02; 95% CI, 0.82-5.02, p = 0.12). Secondary outcomes of time to intubation, lowest arterial oxygen saturation, complications, and in-hospital mortality were not different between video and direct laryngoscopy.
CONCLUSIONS - In critically ill adults undergoing endotracheal intubation, video laryngoscopy improves glottic visualization but does not appear to increase procedural success or decrease complications.
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