Publications by authors named "Colin K Grissom"

106 Publications

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

J Am Med Inform Assoc 2021 Feb 16. Epub 2021 Feb 16.

Institute for Healthcare Improvement, Boston, Massachusetts, USA.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.
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http://dx.doi.org/10.1093/jamia/ocaa294DOI Listing
February 2021

Long-Term Implications of Abnormal Left Ventricular Strain During Sepsis.

Crit Care Med 2021 Feb 12. Epub 2021 Feb 12.

Division of Pulmonary, Department of Medicine, Intermountain Medical Center, Salt Lake City, UT. Division of Pulmonary, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT. Division of Pulmonary, Department of Medicine, Boston University, Boston, MA. Division of Cardiothoracic Surgery, University of Utah School of Medicine, Salt Lake City, UT. Division of Emergency Medicine, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT. Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT. Intermountain Medical Center Heart Institute, Intermountain Healthcare, Salt Lake City, UT. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA. Division of Cardiology, Department of Medicine, University of California San Francisco, San Francisco, CA.

Objectives: Septic cardiomyopathy develops frequently in patients with sepsis and likely increases short-term mortality. However, whether septic cardiomyopathy is associated with long-term outcomes after sepsis is unknown. We investigated whether septic patients with septic cardiomyopathy have worse long-term outcomes than septic patients without septic cardiomyopathy.

Design: Retrospective cohort study.

Setting: Adult ICU.

Patients: Adult ICU patients with sepsis.

Interventions: None.

Measurements And Main Results: Left ventricular global longitudinal systolic strain was our primary measure of septic cardiomyopathy. We employed a suite of multivariable survival analyses to explore linear and nonlinear associations between left ventricular global longitudinal systolic strain and major adverse cardiovascular events, which included death, stroke, and myocardial infarction. Our primary outcome was major adverse cardiovascular event through 24 months after ICU discharge. Among 290 study patients, median left ventricular global longitudinal systolic strain was -16.8% (interquartile range, -20.4% to -12.6%), and 38.3% of patients (n = 111) experienced a major adverse cardiovascular event within 24 months after discharge. On our primary, linear analysis, there was a trend (p = 0.08) toward association between left ventricular global longitudinal systolic strain and major adverse cardiovascular event (odds ratio, 1.03; CI, < 1 to 1.07). On our nonlinear analysis, the association was highly significant (p < 0.001) with both high and low left ventricular global longitudinal systolic strain associated with major adverse cardiovascular event among patients with pre-existing cardiac disease. This association was pronounced among patients who were younger (age < 65 yr) and had Charlson Comorbidity Index greater than 5.

Conclusions: Among patients with sepsis and pre-existing cardiac disease who survived to ICU discharge, left ventricular global longitudinal systolic strain demonstrated a U-shaped association with cardiovascular outcomes through 24 months. The relationship was especially strong among younger patients with more comorbidities. These observations are likely of use to design of future trials.
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http://dx.doi.org/10.1097/CCM.0000000000004886DOI Listing
February 2021

Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial.

Ann Am Thorac Soc 2020 Nov 9. Epub 2020 Nov 9.

University of Utah School of Medicine, 12348, Study Design and Biostatistics Center and Division of Epidemiology, Salt Lake City, Utah, United States.

Rationale: The COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates.

Objective: Assess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19.

Methods: We performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective.

Results: We enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury.

Conclusions: While early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation.

Clinical Trial Registration: This trial was prospectively registered (NCT04329832) before enrollment of the first patient.
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http://dx.doi.org/10.1513/AnnalsATS.202008-940OCDOI Listing
November 2020

Right Ventricular Dysfunction in Early Sepsis and Septic Shock.

Chest 2020 Oct 14. Epub 2020 Oct 14.

Critical Care Echocardiography Service, Intermountain Medical Center, St, Murray, UT; Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, UT.

Background: Sepsis is a frequently lethal state, commonly associated with left ventricular (LV) dysfunction. Right ventricular (RV) dysfunction in sepsis is less well understood.

Research Question: In septic patients, how common is RV dysfunction, and is it associated with worse outcomes?

Study Design And Methods: We measured echocardiographic parameters on critically ill patients with severe sepsis or septic shock within the first 24 hours of ICU admission. We defined RV dysfunction as fractional area change (FAC) less than 35% or tricuspid annulus systolic plane excursion (TAPSE) less than 1.6 cm. We defined LV systolic dysfunction as ejection fraction (EF) less than 45% or longitudinal strain greater than -19%. Using logistic regression, we assessed the relationship between 28-day mortality and presence of RV dysfunction and LV systolic dysfunction, controlling for receipt of vasopressors, receipt of fluid, mechanical ventilation, and the acute physiology and chronic health evaluation (APACHE II) score.

Results: We studied 393 patients. RV and LV dysfunction were common (48% and 63%, respectively). Mean echocardiographic values were: RV end-diastolic area, 22.4 ± 7.0 cm; RV end-systolic area, 14.2 ± 6.0 cm; RV FAC, 38 ± 11%; TAPSE, 1.8 ± .06 cm; RV longitudinal strain, -15.3 ± 6.5%; LV EF, 60% ± 14%; LV longitudinal strain, -16.5% ± 6.0%. Patients with RV dysfunction had higher 28-day mortality (31% vs 16%, P = .001). In our multivariable regression model, RV dysfunction was associated with increased mortality (OR, 3.4; CI, 1.7-6.8; P = .001), and LV systolic dysfunction was not (OR, 0.63; CI, 0.3 -1.2; P = .32) INTERPRETATION: Right ventricular dysfunction is present in nearly half of studied septic patients and is associated with over threefold higher 28-day mortality.
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http://dx.doi.org/10.1016/j.chest.2020.09.274DOI Listing
October 2020

Multi-factorial barriers and facilitators to high adherence to lung-protective ventilation using a computerized protocol: a mixed methods study.

Implement Sci Commun 2020 28;1(1):67. Epub 2020 Jul 28.

Healthcare Delivery Institute, Intermountain Healthcare, 5026 South State Street 3rd Floor, Murray, UT 84107 USA.

Background: Lung-protective ventilation (LPV) improves outcomes for patients with acute respiratory distress syndrome (ARDS) through the administration of low tidal volumes (≤ 6.5 ml/kg predicted body weight [PBW]) with co-titration of positive end-expiratory pressure and fraction of inspired oxygen. Many patients with ARDS, however, are not managed with LPV. The purpose of this study was to understand the implementation barriers and facilitators to the use of LPV and a computerized LPV clinical decision support (CDS) tool in intensive care units (ICUs) in preparation for a pilot hybrid implementation-effectiveness clinical trial.

Methods: We performed an explanatory sequential mixed methods study from June 2018 to March 2019 to evaluate the variation in LPV adherence across 17 ICUs in an integrated healthcare system with > 4000 mechanically ventilated patients annually. We analyzed 47 key informant interviews of ICU physicians, respiratory therapists (RTs), and nurses in 3 of the ICUs using a qualitative content analysis paradigm to investigate site variation as defined by adherence level (low, medium, high) and to identify barriers and facilitators to LPV and LPV CDS tool use.

Results: Forty-two percent of patients had an initial set tidal volume of ≤ 6.5 ml/kg PBW during the measurement period (site range 21-80%). LPV CDS tool use was 28% (site range 6-91%). This study's main findings revealed multi-factorial facilitators and barriers to use that varied by ICU site adherence level. The primary facilitator was that LPV and the LPV CDS tool could be used on all mechanically ventilated patients. Barriers included a persistent gap between clinician attitudes regarding the use of LPV and actual use, the perceived loss of autonomy associated with using a computerized protocol, the nature of physician-RT interaction in ventilation management, and the lack of clear organization measures of success.

Conclusions: Variation in adherence to LPV persists in ICUs within a healthcare delivery system that was an early adopter of LPV. Potentially promising strategies to increase adherence to LPV and the LPV CDS tool for ARDS patients include initiating low tidal ventilation on all mechanically ventilated patients, establishing and measuring adherence measures, and focused education addressing the physician-RT interaction. These strategies represent a blueprint for a future hybrid implementation-effectiveness trial.
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http://dx.doi.org/10.1186/s43058-020-00057-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385713PMC
July 2020

COVID-19 Lung Injury is Not High Altitude Pulmonary Edema.

High Alt Med Biol 2020 06 13;21(2):192-193. Epub 2020 Apr 13.

Altitude Research Center, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

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http://dx.doi.org/10.1089/ham.2020.0055DOI Listing
June 2020

Unanticipated critical findings on echocardiography in septic patients.

Ultrasound J 2020 Apr 2;12(1):12. Epub 2020 Apr 2.

Pulmonary Division, Intermountain Medical Center, Salt Lake City, UT, USA.

Background: Echocardiography is increasingly performed among septic patients as a routine part of evaluation and management in the intensive care unit (ICU). The rate of unanticipated critical findings (e.g., severe left or right ventricular dysfunction or pericardial tamponade) on such echocardiograms is unknown. We evaluated a retrospective cohort of septic ICU patients in whom transthoracic echocardiography was performed as a routine part of sepsis management. In addition to identifying critical findings, we defined whether each critical finding was anticipated, and whether the clinical team responded to the critical finding. The primary outcome was rate of unanticipated critical findings, which we hypothesized would occur in fewer than 5% of patients. We also performed an exploratory analysis of the association between unanticipated critical finding and mortality, controlling for severity of illness.

Results: We studied 393 patients. Unanticipated critical findings were identified in 5% (95% CI 3-7%) of patients (n = 20). Among the 20 patients with unanticipated critical findings, a response to the unanticipated critical finding was identified in 12 (60%) patients. An unanticipated critical finding was not significantly associated with 28-day mortality when controlling for admission APACHE II (p = 0.27).

Conclusions: Unanticipated critical findings on echocardiograms in septic ICU patients are uncommon. The potential therapeutic relevance of echocardiography to sepsis is more likely related to hemodynamic management than to traditional cardiac diagnoses. Research studies that employ blinded echocardiograms in septic patients may anticipate unblinding for critical findings approximately 1 in every 20 echocardiograms.
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http://dx.doi.org/10.1186/s13089-020-00162-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113332PMC
April 2020

Reply to: Reconsidering the air pocket around mouth and nose as a positive outcome predictor in completely buried avalanche victims.

Resuscitation 2020 07 28;152:210-211. Epub 2020 Mar 28.

Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT 84107, United States.

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http://dx.doi.org/10.1016/j.resuscitation.2020.03.015DOI Listing
July 2020

Driving pressure is not associated with mortality in mechanically ventilated patients without ARDS.

Crit Care 2019 12 27;23(1):424. Epub 2019 Dec 27.

Division of Pulmonary and Critical Care, Intermountain Medical Center, Shock Trauma ICU, 5121 S. Cottonwood Street, Murray, UT, 84107, USA.

Background: In patients with acute respiratory distress syndrome (ARDS), low tidal volume ventilation has been associated with reduced mortality. Driving pressure (tidal volume normalized to respiratory system compliance) may be an even stronger predictor of ARDS survival than tidal volume. We sought to study whether these associations hold true in acute respiratory failure patients without ARDS.

Methods: This is a retrospectively cohort analysis of mechanically ventilated adult patients admitted to ICUs from 12 hospitals over 2 years. We used natural language processing of chest radiograph reports and data from the electronic medical record to identify patients who had ARDS. We used multivariable logistic regression and generalized linear models to estimate associations between tidal volume, driving pressure, and respiratory system compliance with adjusted 30-day mortality using covariates of Acute Physiology Score (APS), Charlson Comorbidity Index (CCI), age, and PaO/FiO ratio.

Results: We studied 2641 patients; 48% had ARDS (n = 1273). Patients with ARDS had higher mean APS (25 vs. 23, p < .001) but similar CCI (4 vs. 3, p = 0.6) scores. For non-ARDS patients, tidal volume was associated with increased adjusted mortality (OR 1.18 per 1 mL/kg PBW increase in tidal volume, CI 1.04 to 1.35, p = 0.010). We observed no association between driving pressure or respiratory compliance and mortality in patients without ARDS. In ARDS patients, both ΔP (OR1.1, CI 1.06-1.14, p < 0.001) and tidal volume (OR 1.17, CI 1.04-1.31, p = 0.007) were associated with mortality.

Conclusions: In a large retrospective analysis of critically ill non-ARDS patients receiving mechanical ventilation, we found that tidal volume was associated with 30-day mortality, while driving pressure was not.
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http://dx.doi.org/10.1186/s13054-019-2698-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935179PMC
December 2019

Early High-Dose Vitamin D for Critically Ill, Vitamin D-Deficient Patients.

N Engl J Med 2019 12 11;381(26):2529-2540. Epub 2019 Dec 11.

The affiliations of the members of the writing committee are as follows: the Department of Emergency Medicine, University of Colorado School of Medicine, Aurora (A.A.G., L.F.); the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (R.G.B.); the Department of Emergency Medicine, Ohio State University, Columbus (J.M.C.); the Departments of Anesthesia, Critical Care, and Pain Medicine (V.M.B.-G., D.T.) and Emergency Medicine (N.I.S.), Beth Israel Deaconess Medical Center, and the Biostatistics Center (D.H.) and the Department of Medicine (N.R., B.T.T.), Massachusetts General Hospital - all in Boston; the Department of Medicine, Intermountain Medical Center and the University of Utah, Salt Lake City (C.K.G.); the Department of Medicine, University of Washington, Seattle (C.L.H.); the Departments of Medicine (R.C.H.) and Surgery (P.K.P.), University of Michigan, Ann Arbor; the Department of Emergency Medicine and Surgery, Henry Ford Hospital, Detroit (E.P.R.); the Department of Medicine, Oregon Health and Science University, Portland (A.K.); the Department of Medicine, Stanford University, Palo Alto, CA (J.E.L.); the Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville (W.H.S.); and the Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh (D.M.Y.).

Background: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D or matched placebo. The primary end point was 90-day all-cause, all-location mortality.

Results: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.

Conclusions: Early administration of high-dose enteral vitamin D did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).
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http://dx.doi.org/10.1056/NEJMoa1911124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306117PMC
December 2019

Avalanche airbag post-burial active deflation - The ability to create an air pocket to delay asphyxiation and prolong survival.

Resuscitation 2020 01 5;146:155-160. Epub 2019 Dec 5.

Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT 84107, United States.

Aim: The primary purpose of an avalanche airbag is to prevent burial during an avalanche. Approximately twenty percent of avalanche victims deploying airbags become critically buried, however. One avalanche airbag actively deflates three minutes after deployment, potentially creating an air pocket. Our objective was to evaluate this air pocket and its potential to prevent asphyxiation.

Methods: Twelve participants were fitted with an airbag and placed prone on the snow. Participants deployed the airbag and were buried in 1.5 m of snow for 60 min with vital signs including oxygen saturation (SpO2) and end-tidal CO2 (ETCO2) measured every minute. Participants completed a post-burial survey to determine head movement within the air pocket.

Results: Eleven of the 12 participants (92%) completed 60 min of burial. Preburial baseline SpO2 measurements did not change significantly over burial time (P > 0.05). Preburial baseline ETCO2 measurements increased over the burial time (P < 0.02); only one ETCO2 value was outside of the normal ETCO2 range (35-45 mmHg). Participants reported they could move their head forward 11.2 cm (SD 4.8 cm) and backward 6.6 cm (SD 5.1 cm) with the majority of participants stated that they had enough head movement to separate the oral cavity from opposing snow if necessary. Visual examination during extrication revealed a well-defined air pocket in all burials.

Conclusion: The avalanche airbag under study creates an air pocket that appears to delay asphyxia, which could allow extra time for rescue and improve overall survival of avalanche victims.
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http://dx.doi.org/10.1016/j.resuscitation.2019.11.023DOI Listing
January 2020

Wilderness Medical Society Clinical Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2019 Update.

Wilderness Environ Med 2019 Dec 15;30(4S):S47-S69. Epub 2019 Nov 15.

Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center and the University of Utah, Salt Lake City, UT.

To provide guidance to clinicians, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and a balance between benefits and risks/burdens according to the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations. This is the 2019 update of the Wilderness Medical Society Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2014 Update.
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http://dx.doi.org/10.1016/j.wem.2019.10.002DOI Listing
December 2019

Clinical presentation, treatment, and short-term outcomes of lung injury associated with e-cigarettes or vaping: a prospective observational cohort study.

Lancet 2019 12 8;394(10214):2073-2083. Epub 2019 Nov 8.

Intermountain Healthcare, Pulmonary and Critical Care Medicine, Salt Lake City, UT, USA.

Background: An ongoing outbreak of lung injury associated with e-cigarettes or vaping (also known as E-VALI or VALI) started in March, 2019, in the USA. The cause, diagnosis, treatment, and course of this disease remains unknown.

Methods: In this multicentre, prospective, observational, cohort study, we collected data on all patients with lung injury associated with e-cigarettes or vaping seen in Intermountain Healthcare, an integrated health system based in Utah, USA, between June 27 and Oct 4, 2019. Telecritical care, based in Salt Lake City, UT, USA, was used as the central repository for case validation, public reporting, and system-wide dissemination of expertise, which included a proposed diagnosis and treatment guideline for lung injury associated with e-cigarettes or vaping. We extracted data on patient presentation, treatment, and short-term follow-up (2 weeks after discharge) from chart review and interviews with patients undertaken by the Utah Department of Health (Salt Lake City, UT, USA).

Findings: 60 patients presented with lung injury associated with e-cigarettes or vaping at 13 hospitals or outpatient clinics in the integrated health system. 33 (55%) of 60 were admitted to an intensive care unit (ICU). 53 (88%) of 60 patients presented with constitutional symptoms, 59 (98%) with respiratory symptoms, and 54 (90%) with gastrointestinal symptoms. 54 (90%) of 60 were given antibiotics and 57 (95%) were given steroids. Six (10%) of 60 patients were readmitted to an ICU or hospital within 2 weeks, three (50%) of whom had relapsed with vaping or e-cigarette use. Of 26 patients who were followed up within 2 weeks, despite clinical and radiographic improvement in all, many had residual abnormalities on chest radiographs (ten [67%] of 15) and pulmonary function tests (six [67%] of nine). Two patients died and lung injury associated with e-cigarettes or vaping was thought to be a contributing factor, but not the cause of death, for both.

Interpretation: Lung injury associated with e-cigarettes or vaping is an emerging illness associated with severe lung injury and constitutional and gastrointestinal symptoms. Increased awareness has led to identification of a broad spectrum of severity of illness in patients who were treated with antibiotics and steroids. Despite improvement, at short-term follow-up many patients had residual abnormalities. Lung injury associated with e-cigarettes or vaping remains a clinical diagnosis with symptoms that overlap infectious and other lung diseases. Maintaining a high index of suspicion for this disease is important as work continues in understanding the cause or causes, optimal therapy, and long-term outcomes of these patients.

Funding: Intermountain Healthcare.
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http://dx.doi.org/10.1016/S0140-6736(19)32679-0DOI Listing
December 2019

The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study.

Intensive Care Med Exp 2019 Oct 24;7(1):57. Epub 2019 Oct 24.

Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Department of Medicine, University of Utah, Salt Lake City, UT, USA.

Background: Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis.

Results: In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > - 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5-67.0) years and admission APACHE II score of 21.0 (16.0-32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p < 10).

Conclusions: In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM.
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http://dx.doi.org/10.1186/s40635-019-0271-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813402PMC
October 2019

In Reply to Dr Bennett.

Wilderness Environ Med 2019 09 8;30(3):334-335. Epub 2019 Aug 8.

Intermountain Medical Center, Murray, UT.

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http://dx.doi.org/10.1016/j.wem.2019.06.010DOI Listing
September 2019

Sepsis alters the transcriptional and translational landscape of human and murine platelets.

Blood 2019 09 31;134(12):911-923. Epub 2019 Jul 31.

Molecular Medicine Program, University of Utah, Salt Lake City, UT.

There is increasing recognition that platelets have a functional role in the pathophysiology of sepsis, though this role has not been precisely defined. Whether sepsis alters the human platelet transcriptome and translational landscape has never been established. We used parallel techniques of RNA sequencing and ribosome footprint profiling to interrogate the platelet transcriptome and translatome in septic patients and healthy donors. We identified 1806 significantly differentially expressed (false discovery rate <0.05) transcripts in platelets from septic patients. Platelet translational events during sepsis were also upregulated. To explore the relevance of a murine model of sepsis, cecal ligation and puncture (CLP), we compared sepsis-induced changes in platelet gene expression between septic patients and mice subjected to CLP. Platelet transcriptional (ρ = 0.42, = 3.2 × 10) and translational (ρ = 0.65, = 1.09 × 10) changes were significantly correlated between septic patients and mice. We focused on , tracking and validating the expression, regulation, and functional impact of changes in during sepsis. Increased was identified in bone marrow megakaryocytes within 24 hours of sepsis onset. Subsequent increases in were seen in circulating platelets, suggesting dynamic trafficking of the messenger RNA. Transcriptional changes in were accompanied by de novo protein synthesis of αIIb and integrin αIIbβ3 activation. Increased αIIb was associated with mortality in humans and mice. These findings provide previously unrecognized evidence that human and murine sepsis similarly alters the platelet transcriptional and translational landscape. Moreover, is upregulated and functional in sepsis due to trafficking from megakaryocytes and de novo synthesis in platelets and is associated with increased mortality.
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http://dx.doi.org/10.1182/blood.2019000067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753624PMC
September 2019

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2019 Update.

Wilderness Environ Med 2019 Dec 17;30(4S):S19-S32. Epub 2019 Jul 17.

Division of Emergency Medicine, Altitude Research Center, University of Colorado Denver School of Medicine, Denver, CO; Institute for Altitude Medicine, Telluride, CO.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2014.
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http://dx.doi.org/10.1016/j.wem.2019.05.002DOI Listing
December 2019

The authors reply.

Crit Care Med 2019 08;47(8):e724-e726

Center for Humanizing Critical Care, Intermountain Healthcare, Murray, UT, Division of Pulmonary and Critical Care, Department of Medicine, University of Utah, Salt Lake City, UT, Pulmonary Division, Intermountain Medical Center, Murray, UT, Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, UT Division of Pulmonary and Critical Care, Department of Medicine, University of Utah, Salt Lake City, UT, Pulmonary Division, Intermountain Medical Center, Murray, UT Center for Humanizing Critical Care, Intermountain Healthcare, Murray, UT, Division of Pulmonary and Critical Care, Department of Medicine, University of Utah, Salt Lake City, UT, Pulmonary Division, Intermountain Medical Center, Murray, UT Division of Pulmonary and Critical Care, Department of Medicine, University of Utah, Salt Lake City, UT, Pulmonary Division, Intermountain Medical Center, Murray, UT.

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http://dx.doi.org/10.1097/CCM.0000000000003857DOI Listing
August 2019

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update.

Wilderness Environ Med 2019 Dec 24;30(4S):S3-S18. Epub 2019 Jun 24.

Altitude Research Center, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.

To provide guidance to clinicians about best preventive and therapeutic practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each form of acute altitude illness that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2010 and subsequently updated as the WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness in 2014.
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http://dx.doi.org/10.1016/j.wem.2019.04.006DOI Listing
December 2019

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Heat Illness: 2019 Update.

Wilderness Environ Med 2019 Dec 17;30(4S):S33-S46. Epub 2019 Jun 17.

Pulmonary and Critical Care Division, Intermountain Medical Center and the University of Utah, Salt Lake City, UT.

The Wilderness Medical Society convened an expert panel in 2011 to develop a set of evidence-based guidelines for the recognition, prevention, and treatment of heat illness. We present a review of the classifications, pathophysiology, and evidence-based guidelines for planning and preventive measures, as well as best practice recommendations for both field- and hospital-based therapeutic management of heat illness. These recommendations are graded based on the quality of supporting evidence and balance the benefits and risks or burdens for each modality. This is an updated version of the original Wilderness Medical Society Practice Guidelines for the Treatment and Prevention of Heat-Related Illness published in 2013.
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http://dx.doi.org/10.1016/j.wem.2018.10.004DOI Listing
December 2019

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.

N Engl J Med 2019 05 19;380(21):1997-2008. Epub 2019 May 19.

The affiliations of the members of the writing committee are as follows: the Departments of Medicine (M.M.) and Emergency Medicine (A.A.G.), University of Colorado School of Medicine, Aurora; the Departments of Critical Care Medicine (D.T.H., D.C.A.) and Emergency Medicine (D.M.Y.), University of Pittsburgh School of Medicine, Pittsburgh; the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (R.G.B.); the Interdepartmental Division of Critical Care Medicine, Department of Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto (N.D.F.); the Department of Medicine, Montefiore Hospital, New York (M.N.G.); the Department of Medicine, Intermountain Medical Center and the University of Utah, Salt Lake City (C.K.G.); the Department of Medicine, University of Washington, Seattle (S.G., C.L.H.); the Biostatistics Center (D.H.), the Department of Medicine (B.T.T.), and the PETAL Network Clinical Coordinating Center (C.A.U.), Massachusetts General Hospital, the Department of Emergency Medicine, Division of Emergency Critical Care Medicine, Brigham and Women's Hospital (P.C.H.), and the Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center (D.T.) - all in Boston; the Department of Critical Care, Respiratory Institute, Cleveland Clinic, Cleveland (R.D.H.); the Department of Medicine, University of Michigan and Veterans Affairs Center for Clinical Research, Ann Arbor (T.J.I.); the Department of Medicine, Oregon Health and Science University, Portland (A.K.); and the Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco (K.D.L.).

Background: The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear.

Methods: We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days.

Results: The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months.

Conclusions: Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).
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http://dx.doi.org/10.1056/NEJMoa1901686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741345PMC
May 2019

Cause of Death in Utah Avalanche Fatalities, 2006-2007 through 2017-2018 Winter Seasons.

Wilderness Environ Med 2019 Jun 17;30(2):191-194. Epub 2019 Apr 17.

Utah Avalanche Center, Salt Lake City, UT.

Introduction: Understanding patterns of avalanche fatalities can aid prevention and rescue strategies. In 2007, we published a report reviewing avalanche deaths in Utah between the 1989-1990 and 2005-2006 winter seasons. In the current report, we discuss Utah avalanche fatalities from the 2006-2007 to 2017-2018 seasons.

Methods: Avalanche fatality data were obtained from the Utah Avalanche Center and Utah State Office of the Medical Examiner. Autopsy reports were reviewed to determine demographic information, type of autopsy (external vs internal), injuries, and cause of death.

Results: Thirty-two avalanche deaths occurred in Utah during the study period. The mean (±SD) age of victims was 32±13 (8-54) y. Thirty victims (94%) were male and 2 (6%) were female. Seventy-two percent of deaths were from asphyxiation, 19% from trauma alone, and 9% from a combination of asphyxiation and trauma. Snowmobilers accounted for the largest percentage of avalanche fatalities (15 victims; 47%) during the 2007-2018 period.

Conclusions: Asphyxia continues to be the most prevalent killer in avalanche burial. Patterns of ongoing avalanche deaths continue to suggest that rapid recovery and techniques that prolong survival while buried may decrease fatality rates. Trauma is a significant factor in many avalanche fatalities. Education and technologies focused on reducing traumatic injuries such as improved education in techniques for avalanche risk avoidance and/or use of avalanche airbags may further decrease fatality rates. Snowmobilers represent an increasing percentage of Utah avalanche deaths and now make up the majority of victims; increased education targeting this demographic in the basics of avalanche rescue gear and avalanche rescue may also reduce fatalities.
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http://dx.doi.org/10.1016/j.wem.2019.02.007DOI Listing
June 2019

A simplified definition of diastolic function in sepsis, compared against standard definitions.

J Intensive Care 2019 20;7:14. Epub 2019 Feb 20.

1Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT 84157 USA.

Background: Guidelines for grading diastolic dysfunction poorly categorize septic patients. We compared how well the American Society of Echocardiography (ASE) 2009 and 2016 definitions and a simplified definition categorized septic patients.

Methods: We studied septic patients who received a transthoracic echocardiogram within 24 h of admission to an ICU. We categorized patients according to ASE 2009 and 2016 definitions and a definition using /', a surrogate for left ventricular filling pressure. We assessed 28-day all-cause mortality and the presence of pre-existing diabetes, hypertension, or myocardial infarction. We tested for associations among diastolic grade, comorbidities, and outcomes using logistic regression.

Results: We studied 398 patients. Mortality was 23%. The simplified definition categorized more patients than ASE 2016 (78% vs. 71%,  = 0.035); both definitions categorized more patients than ASE 2009 (34%,  < 0.001 for both comparisons). Higher grades of diastolic dysfunction were associated with hypertension (ASE 2016, simplified), myocardial infarction (ASE 2009, simplified), and diabetes (simplified). Grade of diastolic dysfunction was not associated with mortality by any definition. Of 199 patients categorized as normal by ASE 2016, 40% had an abnormal /' > 9 and 7% had a severely abnormal /e' > 13.

Conclusions: The ASE 2016 definition categorizes more septic patients than the ASE 2009 definition, but it does not categorize the diastolic function of a third of septic patients. ASE 2016 designates many patients with elevated /' as normal. A simplified definition categorized patients with less ambiguity and is associated with relevant comorbidities.
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http://dx.doi.org/10.1186/s40560-019-0367-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381727PMC
February 2019

Reduced Acetazolamide Dosing in Countering Altitude Illness: A Comparison of 62.5 vs 125 mg (the RADICAL Trial).

Wilderness Environ Med 2019 Mar 8;30(1):12-21. Epub 2019 Jan 8.

Intermountain Medical Center, Murray, UT.

Introduction: North American guidelines propose 125 mg acetazolamide twice daily as the recommended prophylactic dose to prevent acute mountain sickness (AMS). To our knowledge, a dose lower than 125 mg twice daily has not been studied.

Methods: We conducted a prospective, double-blind, randomized, noninferiority trial of trekkers to Everest Base Camp in Nepal. Participants received the reduced dose of 62.5 mg twice daily or the standard dose of 125 mg twice daily. Primary outcome was incidence of AMS, and secondary outcomes were severity of AMS and side effects in each group.

Results: Seventy-three participants had sufficient data to be included in the analysis. Overall incidence of AMS was 21 of 38 (55.3%) in reduced-dose and 21 of 35 (60.0%) in standard-dose recipients. The daily incidence rate of AMS was 6.7% (95% CI 2.5-10.9) for each individual in the reduced-dose group and 8.9% (95% CI 4.5-13.3) in the standard-dose group. Overall severity of participants' Lake Louise Score was 1.014 in the reduced-dose group and 0.966 in the standard-dose group (95% CI 0.885-1.144). Side effects were similar between the groups.

Conclusions: The reduced dose of acetazolamide at 62.5 mg twice daily was noninferior to the currently recommended dose of 125 mg twice daily for the prevention of AMS. Low incidence of AMS in the study population may have limited the ability to differentiate the treatment effects. Further research with more participants with greater rates of AMS would further elucidate this reduced dosage for preventing altitude illness.
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http://dx.doi.org/10.1016/j.wem.2018.09.002DOI Listing
March 2019

Prospective Assessment of the Feasibility of a Trial of Low-Tidal Volume Ventilation for Patients with Acute Respiratory Failure.

Ann Am Thorac Soc 2019 03;16(3):356-362

18 Baystate Medical Center, Springfield, Massachusetts.

Rationale: Low-tidal volume ventilation (LTVV; 6 ml/kg) benefits patients with acute respiratory distress syndrome and may aid those with other causes of respiratory failure. Current early ventilation practices are poorly defined.

Objectives: We observed patients with acute respiratory failure to assess the feasibility of a pragmatic trial of LTVV and to guide experimental design.

Methods: We prospectively enrolled consecutive patients with acute respiratory failure admitted to intensive care units expected to participate in the proposed trial. We collected clinical data as well as information on initial and daily ventilator settings and inpatient mortality. We estimated the benefit of LTVV using predictive linear and nonlinear models. We simulated models to estimate power and feasibility of a cluster-randomized trial of LTVV versus usual care in acute respiratory failure.

Results: We included 2,484 newly mechanically ventilated patients (31% with acute respiratory distress syndrome) from 49 hospitals. Hospital mortality was 28%. Mean initial tidal volume was 7.1 ml/kg predicted body weight (95% confidence interval, 7.1-7.2), with 78% of patients receiving tidal volumes less than or equal to 8 ml/kg. Our models estimated a mortality benefit of 0-2% from LTVV compared with usual care. Simulation of a stepped-wedged cluster-randomized trial suggested that enrollment of 106,361 patients would be necessary to achieve greater than 90% power.

Conclusions: Use of initial tidal volumes less than 8 ml/kg predicted body weight was common at hospitals participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. After considering the size and budgetary requirement for a cluster-randomized trial of LTVV versus usual care in acute respiratory failure, the PETAL Network deemed the proposed trial infeasible. A rapid observational study and simulations to model anticipated power may help better design trials.
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http://dx.doi.org/10.1513/AnnalsATS.201807-459OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394119PMC
March 2019

Randomized Feasibility Trial of a Low Tidal Volume-Airway Pressure Release Ventilation Protocol Compared With Traditional Airway Pressure Release Ventilation and Volume Control Ventilation Protocols.

Crit Care Med 2018 12;46(12):1943-1952

Division of Pulmonary and Critical Care, Department of Medicine, University of Utah, Salt Lake City, UT.

Objectives: Low tidal volume (= tidal volume ≤ 6 mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable and can exceed tidal volume breaths of low tidal volume-volume control. We evaluate the application of a low tidal volume-compatible airway pressure release ventilation protocol that manages release volumes on both clinical and feasibility endpoints.

Design: We designed a prospective randomized trial in patients with acute hypoxemic respiratory failure. We randomized patients to low tidal volume-volume control, low tidal volume-airway pressure release ventilation, and traditional airway pressure release ventilation with a planned enrollment of 246 patients. The study was stopped early because of low enrollment and inability to consistently achieve tidal volumes less than 6.5 mL/kg in the low tidal volume-airway pressure release ventilation arm. Although the primary clinical study endpoint was PaO2/FIO2 on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms.

Setting: Four Intermountain Healthcare tertiary ICUs.

Patients: Adult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation.

Interventions: Low tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation.

Measurements And Main Results: We observed wide variability and higher tidal (release for airway pressure release ventilation) volumes in both airway pressure release ventilation (8.6 mL/kg; 95% CI, 7.8-9.6) and low tidal volume-airway pressure release ventilation (8.0; 95% CI, 7.3-8.9) than volume control (6.8; 95% CI, 6.2-7.5; p = 0.005) with no difference between airway pressure release ventilation and low tidal volume-airway pressure release ventilation (p = 0.58). Recognizing the limitations of small sample size, we observed no difference in 52 patients in day 3 PaO2/ FIO2 (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax.

Conclusions: Airway pressure release ventilation resulted in release volumes often exceeding 12 mL/kg despite a protocol designed to target low tidal volume ventilation. Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway pressure release ventilation is not feasible at this time in the absence of an explicit, generalizable, and reproducible low tidal volume-airway pressure release ventilation protocol.
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http://dx.doi.org/10.1097/CCM.0000000000003437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250244PMC
December 2018

The authors reply.

Crit Care Med 2018 10;46(10):e1013-e1014

Division of Pulmonary, Department of Medicine, Intermountain Medical Center, Murray, UT, and Division of Pulmonary and Critical Care, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA Department of Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA Department of Anesthesia, Stanford University, Stanford, CA Division of Pulmonary, Department of Medicine, Intermountain Medical Center, Murray, UT, and Division of Pulmonary and Critical Care, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT Division of Pulmonary, Department of Medicine, Intermountain Medical Center, Murray, UT Department of Anesthesia, University of Chicago, Chicago, IL Division of Pulmonary, Department of Medicine, Intermountain Medical Center, Murray, UT, and Division of Pulmonary and Critical Care, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.

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http://dx.doi.org/10.1097/CCM.0000000000003331DOI Listing
October 2018

Rebuttal From Drs Grissom and Brown.

Chest 2018 09;154(3):484-485

Pulmonary and Critical Care, Intermountain Medical Center; and Pulmonary and Critical Care, University of Utah, Salt Lake City, UT.

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http://dx.doi.org/10.1016/j.chest.2018.06.013DOI Listing
September 2018

POINT: Should Computerized Protocols Replace Physicians for Managing Mechanical Ventilation? Yes.

Chest 2018 09;154(3):479-481

Pulmonary and Critical Care, Intermountain Medical Center; and Pulmonary and Critical Care, University of Utah, Salt Lake City, UT.

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http://dx.doi.org/10.1016/j.chest.2018.06.009DOI Listing
September 2018

Esmolol infusion in patients with septic shock and tachycardia: a prospective, single-arm, feasibility study.

Pilot Feasibility Stud 2018 3;4:132. Epub 2018 Aug 3.

6Department of Anesthesia, University of Chicago, Chicago, IL USA.

Background: High adrenergic tone appears to be associated with mortality in septic shock, while adrenergic antagonism may improve survival. In preparation for a randomized trial, we conducted a prospective, single-arm pilot study of esmolol infusion for patients with septic shock and tachycardia that persists after adequate volume expansion.

Methods: From April 2016 to March 2017, we enrolled patients admitted to an intensive care unit with sepsis who were receiving vasopressor infusion and were tachycardic despite adequate volume expansion. All patients received a continuous intravenous infusion of esmolol, targeted to heart rate 80-90/min, while receiving vasopressors. The feasibility outcomes were proportion of eligible patients consented, compliance with pre-infusion safety check, and compliance with the titration protocol. The primary clinical outcome was organ-failure-free days (OFFD) at 28 days.

Results: We enrolled 7 of 10 eligible patients. Mean age was 46 (± 19) years, and mean admission APACHE II was 28 (± 8). Median norepinephrine infusion rate at the initiation of esmolol infusion was 0.20 (0.14-0.23) μg/kg/min. Compliance with the safety check was 100%; compliance with components of the titration protocol was 98-100%. OFFD were 26 (24.5-26); all patients survived to day 90. Median peak esmolol infusion was 50 (25-50) μg/kg/min. Median peak norepinephrine infusion rate during esmolol infusion was 0.46 (0.13-0.50) μg/kg/min. Four patients achieved target heart rate. Protocol-defined stop events, suggesting possible intolerance to a given infusion rate, occurred in three patients, all of whom were receiving at least 50 μg/kg/min of esmolol.

Conclusions: In a pilot, single-arm study, we report the first published experience with esmolol infusion in tachycardic patients with septic shock in the United States. These findings support a phase 2 trial of esmolol infusion for septic shock. Lower infusion rates of esmolol infusion may be better tolerated and more feasible than higher infusion rates for such a trial.

Trial Registration: This study was retrospectively registered at ClinicalTrials.gov (NCT02841241) on 19 July 2016.
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http://dx.doi.org/10.1186/s40814-018-0321-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091011PMC
August 2018