Publications by authors named "Kyle J Gunnerson"

35 Publications

Effect of an emergency department intensive care unit on medical intensive unit admissions and care: A retrospective cohort study.

Am J Emerg Med 2021 Feb 24;46:27-33. Epub 2021 Feb 24.

Pulmonary and Critical Care Department, The University of Michigan Health System, MI, USA. Electronic address:

Objective: Evaluate the impact of an emergency critical care center (EC3) on the admissions of critically ill patients to a critical care medicine unit (CCMU) and their outcomes.

Methods: This was a retrospective before/after cohort study in a tertiary university teaching hospital. To improve the care of critically ill patients in the emergency department (ED), a 9-bed EC3 was opened in the ED in February 2015. All critically ill patients in the emergency department must receive intensive support in EC3 before being considered for admission to the CCMU for further treatment. Patients from the emergency department account for a significant proportion of the patients admitted to the CCMU. The proportions of patients admitted to the CCMU from the ED were analyzed 1 year before and 1 year after the opening of the EC3. We also compared the admission data, demographic data, APACHE III scores and patient outcomes among patients admitted from ED to the CCMU in the year before and the year after the opening of the EC3.

Result: The establishment of the EC3 was associated with a decreased proportion of patients admitted to the CCMU from the ED (OR 0.73 95% CI 0.63-0.84, p < 0.01), a decrease in the proportion of patients with sepsis admitted from the ED (OR 0.68, 95% CI, 0.54-0.87, p < 0.01) and a decrease in the proportion of patients with gastrointestinal bleeding admitted from the ED (OR 0.49, 95% CI 0.28-0.84, p < 0.05). Following the establishment of the EC3, patients admitted to the CCMU had a higher APACHE III score in 2015 (74.85 ± 30.42 vs 72.39 ± 29.64, p = 0.015). Fewer low-risk patients were admitted to the CCMU for monitoring following the opening of the EC3 (112 [6.8%] vs. 181 [9.3%], p < 0.01). Propensity score matching analysis showed that the opening of the EC3 was associated with improved 60-day survival (HR 0.84, 95% CI 0.70-0.99, p = 0.046).

Conclusion: Following the opening of the EC3, the proportion of CCMU admissions from the ED decreased. The EC3 may be most effective at reducing the admission of lower-acuity patients with GI bleeding and possibly sepsis. The EC3 may be associated with improved survival in ED patients.
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February 2021

Use of Biomarkers to Identify Acute Kidney Injury to Help Detect Sepsis in Patients With Infection.

Crit Care Med 2021 04;49(4):e360-e368

Department of Medicine, Veterans Affairs Medical Center, San Diego, CA.

Objectives: Although early recognition of sepsis is vital to improving outcomes, the diagnosis may be missed or delayed in many patients. Acute kidney injury is one of the most common organ failures in patients with sepsis but may not be apparent on presentation. Novel biomarkers for acute kidney injury might improve organ failure recognition and facilitate earlier sepsis care.

Design: Retrospective, international, Sapphire study.

Setting: Academic Medical Center.

Patients: Adults admitted to the ICU without evidence of acute kidney injury at time of enrollment.

Interventions: None.

Measurements And Main Results: We stratified patients enrolled in the Sapphire study into three groups-those with a clinical diagnosis of sepsis (n = 216), those with infection without sepsis (n = 120), and those without infection (n = 387) at enrollment. We then examined 30-day mortality stratified by acute kidney injury within each group. Finally, we determined the operating characteristics for kidney stress markers (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) for prediction of acute kidney injury as a sepsis-defining organ failure in patients with infection without a clinical diagnosis of sepsis at enrollment. Combining all groups, 30-day mortality was 23% for patients who developed stage 2-3 acute kidney injury within the first 3 days compared with 14% without stage 2-3 acute kidney injury. However, this difference was greatest in the infection without sepsis group (34% vs 11%; odds ratio, 4.09; 95% CI, 1.53-11.12; p = 0.005). Using a (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) cutoff of 2.0 units, 14 patients (11.7%), in the infection/no sepsis group, tested positive of which 10 (71.4%) developed stage 2-3 acute kidney injury. The positive test result occurred a median of 19 hours (interquartile range, 0.8-34.0 hr) before acute kidney injury manifested by serum creatinine or urine output. Similar results were obtained using a cutoff of 1.0 for any stage of acute kidney injury.

Conclusions: Use of the urinary (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) test could identify acute kidney injury in patients with infection, possibly helping to detect sepsis, nearly a day before acute kidney injury is apparent by clinical criteria.
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April 2021

Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport.

Ann Emerg Med 2021 Feb 1. Epub 2021 Feb 1.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI; Michigan Center for Integrative Research in Critical Care, University of Michigan Medical School, Ann Arbor, MI; Extracorporeal Life Support Laboratory, University of Michigan Medical School, Ann Arbor, MI.

Study Objective: Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients.

Methods: In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes.

Results: Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome.

Conclusion: The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.
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February 2021

Resonance Raman Spectroscopy Derived Tissue Hemoglobin Oxygen Saturation in Critically Ill and Injured Patients.

Shock 2020 Nov 17. Epub 2020 Nov 17.

Department of Emergency Medicine. University of Michigan, Ann Arbor, Michigan.

Background: In this study, we examined the ability of resonance Raman spectroscopy to measure tissue hemoglobin oxygenation (R-StO2) noninvasively in critically ill patients and compared its performance with conventional central venous hemoglobin oxygen saturation (ScvO2).

Methods: Critically ill patients (n = 138) with an indwelling central venous or pulmonary artery catheter in place were consented and recruited. R-StO2 measurements were obtained by placing a sensor inside the mouth on the buccal mucosa. R-StO2 was measured continuously for 5 minutes. Blood samples were drawn from the distal port of the indwelling central venous catheter or proximal port of the pulmonary artery catheter at the end of the test period to measure ScvO2 using standard co-oximetry analyzer. A regression algorithm was used to calculate the R-StO2 based on the observed spectra.

Results: Mean(SD) of pooled R-StO2 and ScvO2 were 64(7.6) % and 65(9.2) % respectively. A paired t-test showed no significant difference between R-StO2 and ScvO2 with a mean(SD) difference of -1(7.5) % (95% CI: -2.2, 0.3%) with a Clarke Error Grid demonstrating 84.8% of the data residing within the accurate and acceptable grids. Area under the receiver operator curve for R-StO2's was 0.8(0.029) (95% CI: 0.7, 0.9 p < 0.0001) at different thresholds of ScvO2 (≤60%, ≤65%, and ≤70%). Clinical adjudication by five clinicians to assess the utility of R-StO2 and ScvO2 yielded Fleiss' Kappa agreement of 0.45 (p < 0.00001).

Conclusions: R-StO2 has the potential to predict ScvO2 with high precision and might serve as a faster, safer, and non-invasive surrogate to these measures.
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November 2020

Angiotensin II Infusion for Shock: A Multicenter Study of Postmarketing Use.

Chest 2021 Feb 31;159(2):596-605. Epub 2020 Aug 31.

Department of Pharmacy, Mayo Clinic, Rochester, MN; Multidisciplinary Epidemiology and Translational Research in Intensive Care, Mayo Clinic, Rochester, MN; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN. Electronic address:

Background: Vasodilatory shock refractory to catecholamine vasopressors and arginine vasopressin is highly morbid and responsible for significant mortality. Synthetic angiotensin II is a potent vasoconstrictor that may be suitable for use in these patients.

Research Question: What is the safety and effectiveness of angiotensin II and what variables are associated with a favorable hemodynamic response?

Study Design And Methods: We performed a multicenter, retrospective study at five tertiary medical centers in the United States. The primary end point of hemodynamic responsiveness to angiotensin II was defined as attainment of mean arterial pressure (MAP) of ≥ 65 mm Hg with a stable or reduced total vasopressor dosage 3 h after drug initiation.

Results: Of 270 included patients, 181 (67%) demonstrated hemodynamic responsiveness to angiotensin II. Responders showed a greater increase in MAP (+10.3 mm Hg vs +1.6 mm Hg, P < .001) and reduction in vasopressor dosage (-0.20 μg/kg/min vs +0.04 μg/kg/min; P < .001) compared with nonresponders at 3 h. Variables associated with favorable hemodynamic response included lower lactate concentration (OR 1.11; 95% CI, 1.05-1.17, P < .001) and receipt of vasopressin (OR, 6.05; 95% CI, 1.98-18.6; P = .002). In severity-adjusted multivariate analysis, hemodynamic responsiveness to angiotensin II was associated with reduced likelihood of 30-day mortality (hazard ratio, 0.50; 95% CI, 0.35-0.71; P < .001). Arrhythmias occurred in 28 patients (10%) and VTE was identified in 4 patients.

Interpretation: In postmarketing use for vasopressor-refractory shock, 67% of angiotensin II recipients demonstrated a favorable hemodynamic response. Patients with lower lactate concentrations and those receiving vasopressin were more likely to respond to angiotensin II. Patients who responded to angiotensin II experienced reduced mortality.
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February 2021

Emergency Department-based Intensive Care Unit Use Peaks Near Emergency Department Shift Turnover.

West J Emerg Med 2020 Jul 6;21(4):866-870. Epub 2020 Jul 6.

Michigan Medicine, Department of Emergency Medicine, Ann Arbor, Michigan.

Introduction: The Emergency Critical Care Center (EC3) is an emergency department-based intensive care unit (ED-ICU) designed to improve timely access to critical care for ED patients. ED patients requiring intensive care are initially evaluated and managed in the main ED prior to transfer to a separate group of ED-ICU clinicians. The timing of patient transfers to the ED-ICU may decrease the number of handoffs between main ED teams and have an impact on both patient outcomes and optimal provider staffing models, but has not previously been studied. We aimed to analyze patterns of transfer to the ED-ICU and the relationship with shift turnover times in the main ED. We hypothesized that the number of transfers to the ED-ICU increases near main ED shift turnover times.

Methods: An electronic health record search identified all patients managed in the ED and ED-ICU in 2016 and 2017. We analyzed the number of ED arrivals per hour, the number of ED-ICU consults per hour, the time interval from ED arrival to ED-ICU consult, the distribution throughout the day, and the relationship with shift turnover times in the main ED.

Results: A total of 160,198 ED visits were queried, of which 5308 (3.3%) were managed in the ED-ICU. ED shift turnover times were 7 am, 3 pm, and 11 pm. The mean number of ED-ICU consults placed per hour was 221 (85 standard deviation), with relative maximums occurring near ED turnover times: 10:31 pm-11:30 pm (372) and 2:31 pm-3:30 pm (365). The minimum was placed between 7:31 am - 8:30 am (88), shortly after the morning ED turnover time. The median interval from ED arrival time to ED-ICU consult order was 161 minutes (range 6-1,434; interquartile range 144-174). Relative minimums were observed for patients arriving shortly prior to ED turnover times: 4:31 am - 5:30 am (120 minutes [min]), 12:31 pm - 1:30 pm (145 min), and 9:31 pm - 10:30 pm (135 min). Relative maximums were observed for patients arriving shortly after ED turnover times: 7:31 am - 8:30 am (177 min), 4:31 pm - 5:30 pm (218 min), and 11:31 pm - 12:30 am (179 min).

Conclusion: ED-ICU utilization was highest near ED shift turnover times, and utilization was dissimilar to overall ED arrival patterns. Patients arriving immediately prior to ED shift turnover received earlier consults to the ED-ICU, suggesting these patients may have been preferentially transferred to the ED-ICU rather than signed out to the next team of emergency clinicians. These findings may guide operational planning, staffing models, and timing of shift turnover for other institutions implementing ED-ICUs. Future studies could investigate whether an ED-ICU model improves critically ill patients' outcomes by minimizing ED provider handoffs.
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July 2020

Joint Society of Critical Care Medicine-Extracorporeal Life Support Organization Task Force Position Paper on the Role of the Intensivist in the Initiation and Management of Extracorporeal Membrane Oxygenation.

Crit Care Med 2020 06;48(6):838-846

Columbia University College of Physicians & Surgeons/New York-Presbyterian Hospital, New York, NY.

Objectives: To define the role of the intensivist in the initiation and management of patients on extracorporeal membrane oxygenation.

Design: Retrospective review of the literature and expert consensus.

Setting: Series of in-person meetings, conference calls, and emails from January 2018 to March 2019.

Subjects: A multidisciplinary, expert Task Force was appointed and assembled by the Society of Critical Care Medicine and the Extracorporeal Life Support Organization. Experts were identified by their respective societies based on reputation, experience, and contribution to the field.

Interventions: A MEDLINE search was performed and all members of the Task Force reviewed relevant references, summarizing high-quality evidence when available. Consensus was obtained using a modified Delphi process, with agreement determined by voting using the RAND/UCLA scale, with score ranging from 1 to 9.

Measurements And Main Results: The Task Force developed 18 strong and five weak recommendations in five topic areas of extracorporeal membrane oxygenation initiation and management. These recommendations were organized into five areas related to the care of patients on extracorporeal membrane oxygenation: patient selection, management, mitigation of complications, coordination of multidisciplinary care, and communication with surrogate decision-makers. A common theme of the recommendations is extracorporeal membrane oxygenation is best performed by a multidisciplinary team, which intensivists are positioned to engage and lead.

Conclusions: The role of the intensivist in the care of patients on extracorporeal membrane oxygenation continues to evolve and grow, especially when knowledge and familiarity of the issues surrounding extracorporeal membrane oxygenation selection, cannulation, and management are applied.
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June 2020

An Emergency Department-Based Intensive Care Unit is Associated with Decreased Hospital and Intensive Care Unit Utilization for Diabetic Ketoacidosis.

J Emerg Med 2020 Apr 13;58(4):620-626. Epub 2019 Dec 13.

University of Michigan, Ann Arbor, Michigan.

Background: Many emergency department (ED) patients in diabetic ketoacidosis (DKA) are admitted to an inpatient intensive care unit (ICU), while ICU capacity is under increasing strain. The Emergency Critical Care Center (EC3), a hybrid ED-ICU setting, opened with the goal of providing rapid initiation of ICU care in the ED.

Objective: We sought to evaluate the impact of an ED-ICU on disposition and safety outcomes for adult ED patients in DKA.

Methods: This was a retrospective pre-post cohort of ED visits from 2012-2018 at a single academic medical center. Adult ED patients in DKA (pH < 7.30, HCO < 18 mEq/L, anion gap > 14, and glucose > 250 mg/dL) immediately before (pre-EC3) and after (post-EC3) opening of an ED-ICU were identified. ED disposition and safety data were collected and analyzed.

Results: We identified 631 patient encounters: 217 pre-EC3 and 414 post-EC3. Baseline demographics were similar between cohorts. Fewer patients in the post-EC3 cohort were admitted to an ICU (11.6% vs. 23.5%, p < 0.001, number needed to treat [NNT] = 8) or general floor bed (58.0% vs. 73.3%, p < 0.001, NNT = 6), and more were discharged from the ED (27.1% vs. 1.4%, p < 0.001, NNT = 4). Rates of hypokalemia (10.1% vs. 6.0%, p = 0.08) and admission to non-ICU with transfer to ICU within 24 h (0.5% vs. 0%, p = 0.30) did not differ.

Conclusion: Management of patients with DKA in an ED-ICU was associated with decreased ICU and hospital utilization with similar safety outcomes. Managing rapidly reversible critical illnesses in an ED-ICU may help obviate increasing strain facing many health care systems.
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April 2020

Association of an Emergency Department-Based Intensive Care Unit With Survival and Inpatient Intensive Care Unit Admissions.

JAMA Netw Open 2019 07 3;2(7):e197584. Epub 2019 Jul 3.

Department of Emergency Medicine, Michigan Medicine, University of Michigan, Ann Arbor.

Importance: Increased patient acuity, decreased intensive care unit (ICU) bed availability, and a shortage of intensivist physicians have led to strained ICU capacity. The resulting increase in emergency department (ED) boarding time for patients requiring ICU-level care has been associated with worse outcomes.

Objective: To determine the association of a novel ED-based ICU, the Emergency Critical Care Center (EC3), with 30-day mortality and inpatient ICU admission.

Design, Setting, And Participants: This retrospective cohort study used electronic health records of all ED visits between September 1, 2012, and July 31, 2017, with a documented clinician encounter at a large academic medical center in the United States with approximately 75 000 adult ED visits per year. The pre-EC3 cohort included ED patients from September 2, 2012, to February 15, 2015, when the EC3 opened, and the post-EC3 cohort included ED patients from February 16, 2015, to July 31, 2017. Data analyses were conducted from March 2, 2018, to May 28, 2019.

Exposures: Implementation of EC3, an ED-based ICU designed to provide rapid initiation of ICU-level care in the ED setting and seamless transition to inpatient ICUs.

Main Outcomes And Measures: The main outcomes were 30-day mortality among ED patients and rate of ED to ICU admission.

Results: A total of 349 310 visits from a consecutive sample of ED patients (mean [SD] age, 48.5 [19.7] years; 189 709 [54.3%] women) were examined; the pre-EC3 cohort included 168 877 visits and the post-EC3 cohort included 180 433 visits. Implementation of EC3 was associated with a statistically significant reduction in risk-adjusted 30-day mortality among all ED patients (pre-EC3, 2.13%; post-EC3, 1.83%; adjusted odds ratio, 0.85; 95% CI, 0.80-0.90; number needed to treat, 333 patient encounters; 95% CI, 256-476). The risk-adjusted rate of ED admission to ICU decreased with implementation of EC3 (pre-EC3, 3.2%; post-EC3, 2.7%; adjusted odds ratio, 0.80; 95% CI, 0.76-0.83; number needed to treat, 179 patient encounters; 95% CI, 149-217).

Conclusions And Relevance: Implementation of a novel ED-based ICU was associated with improved 30-day survival and reduced inpatient ICU admission. Additional research is warranted to further explore the value of this novel care delivery model in various health care systems.
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July 2019

Simulation training enables emergency medicine providers to rapidly and safely initiate extracorporeal cardiopulmonary resuscitation (ECPR) in a simulated cardiac arrest scenario.

Resuscitation 2019 05 9;138:68-73. Epub 2019 Mar 9.

Department of Emergency Medicine, University of Michigan Medical School, Michigan Medicine, Ann Arbor, Michigan, USA; The Michigan Center for Integrative Research in Critical Care (MCIRCC), University of Michigan Medical School, Michigan Medicine, Ann Arbor, Michigan, USA. Electronic address:

Background: Extracorporeal cardiopulmonaryresuscitation (ECPR) is emerging as a viable rescue strategy for refractory out-of-hospital cardiac arrest. In the U.S., limited training of emergency medicine providers is a barrier to widespread implementation.

Aims: Test the hypothesis that emergency medicine physicians and nurses can acquire and retain the skills to rapidly and safely initiate ECPR using high-fidelity simulation.

Study Design: Prospective interventional study.

Setting: U.S. tertiary academic medical center.

Subjects: Emergency medicine physicians and nurses with no prior ECPR/ECMO experience.

Methods: Teams of three physicians and three nurses underwent a two-day ECPR training course including didactics, hands-on training, and simulation. Teams were videotaped initiating ECPR in a high-fidelity simulation scenario before and after simulation training. The primary outcome was the proportion of simulations in which full ECPR support was achieved within 30 min of patient arrival.

Results: Five teams completed the entire study. Full ECPR support was achieved within 30 min of patient arrival in 11/15, 15/15, and 15/15 attempts at baseline (B), post-testing (PT) and 3-month post-testing (3-PT), respectively (p = 0.06). Intervals (mean ± sd) required to achieve full ECPR support at B, PT, and 3-PT were 25.8±5.3, 17.2±4.6, and 19.2±1.9 min respectively (p < 0.05 for B vs. PT and 3-PT).

Conclusion: High fidelity simulation training is effective in preparing emergency medicine physicians and nurses to rapidly and safely initiate ECPR in a simulated cardiac arrest scenario, and should be considered when implementing an ED-based ECPR program.
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May 2019

The Two-Bag Method for Treatment of Diabetic Ketoacidosis in Adults.

J Emerg Med 2018 05 5;54(5):593-599. Epub 2018 Apr 5.

Department of Emergency Medicine, Michigan Medicine, Ann Arbor, Michigan; Division of Emergency Critical Care, Michigan Medicine, Ann Arbor, Michigan; Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Michigan Medicine, Ann Arbor, Michigan.

Background: The "two-bag method" of management of diabetic ketoacidosis (DKA) allows for titration of dextrose delivery by adjusting the infusions of two i.v. fluid bags of varying dextrose concentrations while keeping fluid, electrolyte, and insulin infusion rates constant.

Objective: We aimed to evaluate the feasibility and potential benefits of this strategy in adult emergency department (ED) patients with DKA.

Methods: This is a before-and-after comparison of a protocol using the two-bag method operationalized in our adult ED in 2015. A retrospective electronic medical record search identified adult ED patients presenting with DKA from January 1, 2013 to June 30, 2016. Clinical and laboratory data, timing of medical therapies, and safety outcomes were collected and analyzed.

Results: Sixty-eight patients managed with the two-bag method (2B) and 107 patients managed with the one-bag method (1B) were identified. The 2B and 1B groups were similar in demographics and baseline metabolic derangements, though significantly more patients in the 2B group received care in a hybrid ED and intensive care unit setting (94.1% vs. 51.4%; p < 0.01). 2B patients experienced a shorter interval to first serum bicarbonate ≥ 18 mEq/L (13.4 vs. 20.0 h; p < 0.05), shorter duration of insulin infusion (14.1 vs. 21.8 h; p < 0.05), and fewer fluid bags were charged to the patient (5.2 vs. 29.7; p < 0.01). Frequency of any measured hypoglycemia or hypokalemia trended in favor of the 2B group (2.9% vs. 10.3%; p = 0.07; 16.2% vs. 27.1%; p = 0.09; respectively), though did not reach significance.

Conclusions: The 2B method appears feasible for management of adult ED patients with DKA, and use was associated with earlier correction of acidosis, earlier discontinuation of insulin infusion, and fewer i.v. fluid bags charged than traditional 1B methods, while no safety concerns were observed.
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May 2018

Physician training in critical care in the United States: Update 2018.

J Trauma Acute Care Surg 2018 06;84(6):963-971

From the Joyce and Don Massey Family Foundation Professor, Department of Surgery (L.M.N.), Departments of Neurosurgery and Neurology (V.R.), Departments of Emergency Medicine, Anesthesiology, and Internal Medicine (K.L.G.), Division of Critical Care Medicine, Department of Anesthesiology (M.D.M.), Frederick G L Huetwell Professor for the Cure and Prevention of Birth Defects and Professor of Pediatrics and Communicable Diseases, Pediatrics-Intensive Care (M.Q.), and Critical Care Medicine Unit (R.C.H.), Department of Medicine, University of Michigan Health System, Ann Arbor, Michigan.

Critical care fellowship training in the United States differs based on specific specialty and includes medicine, surgery, anesthesiology, pediatrics, emergency medicine, and neurocritical care training pathways. We provide an update regarding the number and growth of US critical care fellowship training programs, on-duty residents and certified diplomates, and review the different critical care physician training pathways available to residents interested in pursuing a fellowship in critical care. Data were obtained from the Accreditation Council for Graduate Medical Education and specialty boards (American Board of Internal Medicine, American Board of Surgery, American Board of Anesthesiology, American Board of Pediatrics American Board of Emergency Medicine) and the United Council for Neurologic Subspecialties for the last 16 years (2001-2017). The number of critical care fellowship training programs has increased 22.6%, with a 49.4% increase in the number of on-duty residents annually, over the last 16 years. This is in contrast to the period of 1995 to 2000 when the number of physicians enrolled in critical care fellowship programs had decreased or remained unchanged. Although more than 80% of intensivists in the US train in internal medicine critical care Accreditation Council for Graduate Medical Education-approved fellowships, there has been a significant increase in the number of residents from surgery, anesthesiology, pediatrics, emergency medicine, and other specialties who complete specialty fellowship training and certification in critical care. Matriculation in neurocritical care fellowships is rapidly rising with 60 programs and over 1,200 neurocritical care diplomates. Critical care is now an increasingly popular fellowship in all specialties. This rapid growth of all critical care specialties highlights the magnitude of the heterogeneity that will exist between intensivists in the future.
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June 2018

The Emergency Department's Impact on Inpatient Critical Care Resources.

Kyle J Gunnerson

Acad Emerg Med 2017 10 27;24(10):1283-1285. Epub 2017 Sep 27.

Michigan Medicine, Ann Arbor, MI.

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October 2017

Practice characteristics of Emergency Department extracorporeal cardiopulmonary resuscitation (eCPR) programs in the United States: The current state of the art of Emergency Department extracorporeal membrane oxygenation (ED ECMO).

Resuscitation 2016 10 11;107:38-46. Epub 2016 Aug 11.

Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, 30 North 1900 East, 3C127, Salt Lake City, UT 84132, United States. Electronic address:

Purpose: To characterize the current scope and practices of centers performing extracorporeal cardiopulmonary resuscitation (eCPR) on the undifferentiated patient with cardiac arrest in the emergency department.

Methods: We contacted all US centers in January 2016 that had submitted adult eCPR cases to the Extracorporeal Life Support Organization (ELSO) registry and surveyed them, querying for programs that had performed eCPR in the Emergency Department (ED ECMO). Our objective was to characterize the following domains of ED ECMO practice: program characteristics, patient selection, devices and techniques, and personnel.

Results: Among 99 centers queried, 70 responded. Among these, 36 centers performed ED ECMO. Nearly 93% of programs are based at academic/teaching hospitals. 65% of programs are less than 5 years old, and 60% of programs perform ≤3 cases per year. Most programs (90%) had inpatient eCPR or salvage ECMO programs prior to starting ED ECMO programs. The majority of programs do not have formal inclusion and exclusion criteria. Most programs preferentially obtain vascular access via the percutaneous route (70%) and many (40%) use mechanical CPR during cannulation. The most commonly used console is the Maquet Rotaflow(®). Cannulation is most often performed by cardiothoracic (CT) surgery, and nearly all programs (>85%) involve CT surgeons, perfusionists, and pharmacists.

Conclusions: Over a third of centers that submitted adult eCPR cases to ELSO have performed ED ECMO. These programs are largely based at academic hospitals, new, and have low volumes. They do not have many formal inclusion or exclusion criteria, and devices and techniques are variable.
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October 2016

TIMP2•IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients.

J Trauma Acute Care Surg 2016 Feb;80(2):243-9

From the Departments of Emergency Medicine, Anesthesiology, and Internal Medicine (K.J.G.), Michigan Center for Integrative Research in Critical Care, University of Michigan, Ann Arbor, Michigan; Department of Anesthesia (A.D.S.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Medicine (L.S.C.), Division of Intensive Care Medicine and Division of Nephrology, Veterans Affairs Medical Center, Washington, District of Columbia; Department of Anesthesiology (A.B), University of Florida, Gainesville, Florida; Center for Critical Care Nephrology (A.A.-K., J.A.K.), Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Pulmonary and Critical Care Medicine (K.K.), Mayo Clinic, Rochester, Minnesota; Department of Surgery (M.L.), University of Maryland School of Maryland, Baltimore, Maryland; and Statistical Consultant (J.S., M.G.W.), Carlsbad, California.

Background: Acute kidney injury (AKI) is an important complication in surgical patients. Existing biomarkers and clinical prediction models underestimate the risk for developing AKI. We recently reported data from two trials of 728 and 408 critically ill adult patients in whom urinary TIMP2•IGFBP7 (NephroCheck, Astute Medical) was used to identify patients at risk of developing AKI. Here we report a preplanned analysis of surgical patients from both trials to assess whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) accurately identify surgical patients at risk of developing AKI.

Study Design: We enrolled adult surgical patients at risk for AKI who were admitted to one of 39 intensive care units across Europe and North America. The primary end point was moderate-severe AKI (equivalent to KDIGO [Kidney Disease Improving Global Outcomes] stages 2-3) within 12 hours of enrollment. Biomarker performance was assessed using the area under the receiver operating characteristic curve, integrated discrimination improvement, and category-free net reclassification improvement.

Results: A total of 375 patients were included in the final analysis of whom 35 (9%) developed moderate-severe AKI within 12 hours. The area under the receiver operating characteristic curve for [TIMP-2]•[IGFBP7] alone was 0.84 (95% confidence interval, 0.76-0.90; p < 0.0001). Biomarker performance was robust in sensitivity analysis across predefined subgroups (urgency and type of surgery).

Conclusion: For postoperative surgical intensive care unit patients, a single urinary TIMP2•IGFBP7 test accurately identified patients at risk for developing AKI within the ensuing 12 hours and its inclusion in clinical risk prediction models significantly enhances their performance.

Level Of Evidence: Prognostic study, level I.
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February 2016

Extracorporeal membrane oxygenation (ECMO) for critically ill adults in the emergency department: history, current applications, and future directions.

Crit Care 2015 Dec 17;19:431. Epub 2015 Dec 17.

Arizona Emergency Medicine Research Center, University of Arizona, 1609 N. Warren Ave, Tucson, AZ, 85724, USA.

Extracorporeal membrane oxygenation (ECMO) is a mode of extracorporeal life support that augments oxygenation, ventilation and/or cardiac output via cannulae connected to a circuit that pumps blood through an oxygenator and back into the patient. ECMO has been used for decades to support cardiopulmonary disease refractory to conventional therapy. While not robust, there are promising data for the use of ECMO in acute hypoxemic respiratory failure, cardiac arrest, and cardiogenic shock and the potential indications for ECMO continue to increase. This review discusses the existing literature on the potential use of ECMO in critically ill patients within the emergency department.
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December 2015

Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

Shock 2014 Aug;42(2):99-107

*Department of Emergency Medicine, University of Colorado School of Medicine; and †Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado; ‡Department of Emergency Medicine, Cooper University Hospital and Cooper Medical School of Rowan University, Camden, New Jersey; §Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; ∥New York Methodist Hospital, Brooklyn; and Weill Cornell Medical Center, New York, New York; ¶Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan; **Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; ††Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; ‡‡Departments of Emergency Medicine and Medicine, Loma Linda University Medical Center, Loma Linda, California; §§Departments of Anesthesiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan; ∥∥Departments of Emergency Medicine, and ¶¶Internal Medicine, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, District of Columbia; ***Department of Emergency Medicine, University of North Carolina, Chapel Hill, North Carolina; †††Department of Emergency Medicine, Wayne State University, Detroit, Michigan; and ‡‡‡Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.
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August 2014

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.

Crit Care 2013 Feb 6;17(1):R25. Epub 2013 Feb 6.

Introduction: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.

Methods: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.

Results: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.

Conclusions: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.

Trial Registration: number NCT01209169.
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February 2013

Antecedent bradycardia: an opportunity for pre-arrest intervention?

Kyle J Gunnerson

Resuscitation 2012 Sep 23;83(9):1053-4. Epub 2012 Jun 23.

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September 2012

Relationship between B-type natriuretic peptide and adverse outcome in patients with clinical evidence of sepsis presenting to the emergency department.

Acad Emerg Med 2011 Feb 28;18(2):219-22. Epub 2011 Jan 28.

Beth Israel Deaconess Medical Center, Boston, MA, USA.

Objectives: Myocardial dysfunction is an important aspect of sepsis pathophysiology. B-type natriuretic peptide (BNP) is a neurohormone released from the ventricles in response to myocardial stretch and volume overload. The authors hypothesized that an elevated BNP in patients presenting to the emergency department (ED) with suspected sepsis are at increased risk for development of adverse events.

Methods: This was a prospective, observational, multicenter cohort study in 10 EDs. Patients were eligible if they were older than 18 years, had two or more systemic inflammatory response syndrome (SIRS) criteria, and had suspected infection or a serum lactate level > 2.5 mmol/L. Patients were excluded if they were pregnant, had do-not-attempt-resuscitation status, sustained a cardiac arrest prior to hospital arrival, had known chronic renal insufficiency, or were on dialysis. BNP levels were obtained at arrival. The primary outcome was a composite of severe sepsis, septic shock within 72 hours, or in-hospital mortality.

Results: There were 825 patients enrolled (mean ± standard deviation [SD] age = 53.5 ± 19.6 years; 51% were female and 37% were African American). The area under the curve (AUC) for BNP to predict the triple composite outcome was 0.69, and the optimal cut-point of BNP was 49 pg/mL. Patients with a BNP > 49 pg/mL had a greater mortality rate (11.6% vs. 2.1%; p = 0.0001), a greater risk of development of severe sepsis (67.7% vs. 36.8%; p = 0.0001) and septic shock (51.7% vs. 26.4%; p = 0.0001), and a higher rate of the triple composite outcome (69% vs. 37%; unadjusted odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.6 to 2.1; p < 0.001). The sensitivity was 63% (95% CI = 58% to 67%), specificity was 69% (95% CI = 65% to 73%), negative predictive value (NPV) was 63% (95% CI = 58% to 67%), and positive predictive value (PPV) was 69% (95% CI = 65% to 74%). In multivariate modeling, after adjusting for age, sex, heart rate, white blood cell count, and creatinine, an elevated BNP was associated with increased odds of having the composite outcome. The outcome was similar in the subset of patients who did not have severe sepsis or septic shock upon arrival.

Conclusions: In patients who present to the ED with SIRS criteria and suspected infection, an elevated BNP is associated with a worse prognosis but has limited diagnostic utility.
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February 2011

Antithrombotic therapy for the CardioWest temporary total artificial heart.

Tex Heart Inst J 2010 ;37(2):149-58

Department of Pharmacy, Comprehensive Transplant Center, The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.

The CardioWest temporary total artificial heart serves as a viable bridge to orthotopic heart transplantation in patients who are experiencing end-stage refractory biventricular heart failure. This device is associated with a low, albeit still substantial, risk of thrombosis. Platelet interactions with artificial surfaces are complex and result in continuous activation of contact proteins despite therapeutic anticoagulation. We searched the medical literature (publication dates, January 1962-October 2009) in order to evaluate means of mitigating adverse events that have occurred after implantation of the CardioWest temporary total artificial heart.We conclude that the use of a multitargeted antithrombotic approach, involving anticoagulation (bivalirudin and warfarin) and antiplatelet therapy (dipyridamole and aspirin), can mitigate the procoagulative effects of mechanical circulatory assist devices, particularly those that are associated with the CardioWest temporary total artificial heart. Careful monitoring with use of a variant multisystem approach, involving efficacy tests (thrombelastography and light transmittance aggregometry), safety tests (laboratory analyses), and warfarin genomics, may maximize the therapeutic actions and minimize the bleeding risks that are associated with the multitargeted antithrombotic approach. The development and monitoring of individualized antithrombotic regimens require that informed health professionals appreciate the complexities and grasp the hazards that are associated with these therapies.
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July 2010

Current practice, demographics, and trends of critical care trained emergency physicians in the United States.

Acad Emerg Med 2010 Mar;17(3):325-9

Department of Emergency Medicine, Virginia Commonwealth University Reanimation, Engineering and Shock Center, Virginia Commonwealth University, Richmond, VA, USA.

Objectives: Critical care medicine (CCM) is of growing interest among emergency physicians (EPs), but the number of CCM-trained EPs and their postfellowship practice is unknown. This study's purpose was to conduct a descriptive census survey of EPs who have completed or are currently in a CCM fellowship.

Methods: The authors created a Web-based survey, and requests to participate were sent to EPs who have completed or are currently in a CCM fellowship. Responses were collected over a 12-month period. Physicians were located via multiple whom electronic mailing lists, including the Emergency Medicine Section of the Society of Critical Care Medicine, Critical Care Section of the American College of Emergency Physicians, and the Emergency Medicine Residents' Association. The authors also contacted CCM fellowship coordinators and used informal networking. Data were collected on emergency medicine (EM) and other residency training; discipline, duration, and year of CCM fellowship; current practice setting; and board certification status, including the European Diploma in Intensive Care (EDIC).

Results: A total of 104 physicians completed the survey (97% response rate), of whom 73 had completed fellowship at the time of participation, and 31 of whom were in fellowship training. Of those who completed fellowship, 36/73 (49%) practice both EM and CCM, and 45/73 (62%) practice in academic institutions. Multiple disciplines of fellowship were represented: multidisciplinary (39), surgical (28), internal medicine (16), anesthesia (14), and other (4). Together, the CCM fellowships at the University of Maryland R Adams Cowley Shock Trauma Center and the University of Pittsburgh have trained 42% of all EM-CCM physicians, with 38 other institutions training from one to four fellows each. The number of EPs completing CCM fellowships has risen: from 1974 to 1989, 12 EPs; from 1990 to 1999, 15 EPs; and from 2000 to 2007, 43 EPs.

Conclusions: Emergency physicians are entering CCM fellowships in increasing numbers. Almost half of these EPs practice both EM and CCM.
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March 2010

Is there a difference between strong ion gap in healthy volunteers and intensive care unit patients?

J Crit Care 2010 Sep 25;25(3):520-4. Epub 2009 Nov 25.

The CRISMA Laboratory, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Purpose: Abnormalities of strong ion gap (SIG) are common in critically ill intensive care unit (ICU) patients in conjunction with a high incidence of acid-base abnormalities. However, it is unknown whether abnormalities in SIG are also seen in ICU patients without active acid-base abnormalities. Thus, we conducted this pilot study to examine differences in quantitative acid-base variables between healthy adult volunteers and stable ICU patients with no suspected acid-base abnormalities.

Methods: The study used a prospective observational study of 2 cohorts, 15 healthy adult volunteers and 15 stable adult patients just before ICU discharge who were not receiving renal replacement therapy and had no known active acid-base derangements. We analyzed venous blood for acid-base variables (potential hydrogen in central venous blood [pH(CV)], partial tension of carbon dioxide in central venous blood [p(CV)co(2)], standard base excess [SBE], lactate, Na(+), K(+), Cl(-), Mg(2+), Ca(2+), phosphate, and albumin). From these, we calculated strong ion difference (SID) and SIG for both cohorts.

Results: Although mean values for pH(CV), p(CV)CO(2), and SBE were within the normal range in both cohorts, 10 (66.7%) of 15 of ICU patients were found to have occult acid-base disorders. The ICU patients also had reduced albumin and SID measurements and significantly greater mean SIG (5.1 ± 2.9 mEq/L) compared to healthy controls (1.4 ± 1.8 mEq/L) (P = .0002). None of the healthy controls had a SIG higher than 5.0 mEq/L, whereas 7 (46.7%) of 15 of ICU patients had a SIG higher than 5.0 mEq/L. Even among ICU patients with no abnormalities of pH(CV), p(CV)CO(2), and SBE, mean SIG was 6.4 (± 3.3 mEq/L).

Conclusions: Stable ICU patients have much higher levels of unexplained anions when comparing with healthy controls. Whether this finding represents occult acid-base disorders or simply metabolic differences among the critically ill is uncertain. Further study in larger populations is warranted to establish the significance of high SIG in otherwise stable ICU patients.
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September 2010

A novel noninvasive impedance-based technique for central venous pressure measurement.

Shock 2010 Mar;33(3):269-73

Virginia Commonwealth University, Department of Emergency Medicine, 1201 East Marshall St., P.O. Box 980401, Richmond, VA 23298, USA.

Knowledge of central venous pressure (CVP) is considered valuable in the assessment and treatment of various states of critical illness and injury. We tested a noninvasive means of determining CVP (NICVP) by monitoring upper arm blood flow changes in response to externally applied circumferential pressure to the upper arm veins. Thirty-six patients who were undergoing CVP monitoring as part of their care had NICVP determined and compared with CVP. Volume changes were measured in the upper arm using tetra-polar impedance plethysmography underneath a blood pressure cuff. The cuff was inflated over 5 s to a pressure greater than CVP but less than diastolic arterial pressure. After 45 to 60 s, the cuff was rapidly deflated. Noninvasive CVP was determined as the cuff pressure noted at the maximum derivative of the volume increase under the cuff during deflation. Noninvasive CVP was then compared with invasively measured CVP taken during the same period by Bland-Altman analysis. A total of 108 trials (three per subject) were performed on 36 patients. Mean bias was -0.26 mmHg (95% confidence interval [CI]: -0.67, 0.15). Limits of agreement were -2.7 and 2.2 mmHg with the 95% CI for the lower limit of agreement (-3.4, -2.0 mmHg) and for the upper limit of agreement (1.5, 2.9 mmHg). Correlation between CVP and NICVP was 0.95 (95% CI: 0.93 to 0.97; P < 0.0001). Noninvasive CVP as determined in this study may be a clinically useful substitute for traditional CVP measurement and may offer a tool for early diagnosis and treatment of acute states in which knowledge of CVP would be helpful.
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March 2010

A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis.

Crit Care Med 2009 Jan;37(1):96-104

Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Objective: To define a biomarker panel to predict organ dysfunction, shock, and in-hospital mortality in emergency department (ED) patients with suspected sepsis.

Design: Prospective observational study.

Setting: EDs of ten academic medical centers.

Patients: There were 971 patients enrolled.

Inclusion Criteria: 1) ED patients age > 18; 2) suspected infection or a serum lactate level > 2.5 mmol/L; and 3) two or more systemic inflammatory response syndrome criteria.

Exclusion Criteria: pregnancy, do-not-resuscitate status, or cardiac arrest.

Measurements And Main Results: Nine biomarkers were assayed from blood draws obtained on ED presentation. Multivariable logistic regression was used to identify an optimal combination of biomarkers to create a panel. The derived formula for weighting biomarker values was used to calculate a "sepsis score," which was the predicted probability of the primary outcome of severe sepsis (sepsis plus organ dysfunction) within 72 hrs. We also assessed the ability of the sepsis score to predict secondary outcome measures of septic shock within 72 hrs and in-hospital mortality. The overall rates of each outcome were severe sepsis, 52%; septic shock, 39%; and in-hospital mortality 7%. Among the nine biomarkers tested, the optimal 3-marker panel was neutrophil gelatinase-associated lipocalin, protein C, and interleukin-1 receptor antagonist. The area under the curve for the accuracy of the sepsis score derived from these three biomarkers was 0.80 for severe sepsis, 0.77 for septic shock, and 0.79 for death. When included in multivariate models with clinical variables, the sepsis score remained highly significant (p < 0.001) for all the three outcomes.

Conclusions: A biomarker panel of neutrophil gelatinase-associated lipocalin, interleukin-1ra, and Protein C was predictive of severe sepsis, septic shock, and death in ED patients with suspected sepsis. Further study is warranted to prospectively validate the clinical utility of these biomarkers and the sepsis score in risk-stratifying patients with suspected sepsis.
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January 2009

Successful use and dosing of bivalirudin after temporary total artificial heart implantation: a case series.

Pharmacotherapy 2008 Nov;28(11):1413-20

South University School of Pharmacy, Department of Pharmacy Practice, 709 Mall Boulevard, Savannah, GA 31406-4805, USA.

The temporary total artificial heart (TAH-t) has emerged as an effective bridge to transplantation for individuals with biventricular failure. Implantation of a TAH-t creates a hypercoagulable state requiring a multidrug approach that includes low-dose unfractionated heparin (UFH) in order to minimize thromboembolism. A concern with UFH is the development of heparin-dependent antibodies, which develop in up to 50% of patients receiving the drug as part of cardiopulmonary bypass. If UFH therapy continues postoperatively, the risk of heparin-induced thrombocytopenia approaches 3%. Small investigations have demonstrated that bivalirudin, given as a bolus of 0.75-1 mg/kg followed by an infusion at 1.75-2.5 mg/kg/hour, is an effective alternative to UFH for therapeutic anticoagulation during coronary artery bypass surgery, valve replacement, or both. We describe a series of five adults (age range 24-58 yrs) who received bivalirudin as an alternative to low-dose UFH after TAH-t implantation. None of the patients had documented heparin-induced thrombocytopenia. Treatment was started at the discretion of the treating physician, and adjustments were based principally on the results of thromboelastography. Additional general monitoring included activated partial thromboplastin time, prothrombin time, international normalized ratio, fibrinogen, D-dimer, platelet count, hemoglobin, hematocrit, and platelet aggregation studies. Bivalirudin therapy was continued until successful warfarin implementation. All five patients received bivalirudin in addition to standard antithrombotic therapy. Bivalirudin treatment started at a dosage of 0.005 or 0.01 mg/kg/hour with titration to maintain normocoagulability, which occurred (without concomitant warfarin therapy) within the dosage range of 0.01-0.02 mg/kg/hour. Duration of TAH-t implantation was a mean of 38.8 days (range 25-60 days), and bivalirudin was continued for a mean of 15.2 days (range 7-24 days). No major hemorrhagic events occurred during treatment, and all patients successfully transitioned to warfarin therapy. Low-dose bivalirudin, as an alternative to UFH, maintained normocoagulability after TAH-t implantation. Further investigation is warranted to define the role and dosing of bivalirudin in this situation.
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November 2008

Effects of hypercapnia on BP in hypoalbuminemic and Nagase analbuminemic rats.

Chest 2007 May;131(5):1295-300

MANTRA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.

Study Objective: To determine if animals with abnormally low albumin levels are more susceptible to the effects of hypercapnia on BP compared to normal animals.

Design: Prospective, controlled laboratory experiment.

Setting: University research laboratory.

Animals: Eighteen male Sprague-Dawley rats: 6 rats 10 to 12 weeks old (young Sprague-Dawley [YSD]), 6 rats 6 to 9 months old (old Sprague-Dawley [OSD]), and 6 rats 10 to 12 weeks old (Nagase analbuminemic mutant Sprague-Dawley [NAR]).

Methods: Under general anesthesia and paralysis, we varied the Paco(2) by changing the respiratory rate on mechanical ventilation. Mean arterial pressure (MAP) was monitored in a continuous fashion. We obtained arterial blood for blood gas and electrolyte analysis, and nitric oxide (NO) production.

Results: OSD rats had reduced serum albumin, while NAR rats were analbuminemic. Although NAR animals had a decreased buffer capacity compared to age-matched control animals (0.010 vs 0.013, p < 0.05), the MAP decreased in an identical fashion in all three groups. NO production increased with hypercapnia but was similar in all three groups. However, NAR rats had consistently higher plasma strong ion gap (2.8 to 4.1 mEq/L greater) compared to either YSD or OSD rats (p < 0.01), and baseline strong ion difference (mean +/- SD) was significantly lower in NAR rats (28.7 +/- 2.1 mEq/L) compared to either YSD rats (33.0 +/- 5.1 mEq/L) or OSD rats (31.2 +/- 5.1 mEq/L) [p < 0.05].

Conclusions: These findings suggest that analbuminemic or hypoalbuminemic rats are not more susceptible to hypercapnia-induced hemodynamic instability. Baseline values for apparent strong ion difference are lower in NA rats consistent with a reduced buffer base resulting from analbuminemia.
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May 2007

Early goal-directed therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings.

Chest 2006 Nov;130(5):1579-95

Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.

Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing early goal-directed therapy (EGDT) vs standard care was performed using specific criteria for the early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.
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November 2006

Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients.

Crit Care 2006 Feb;10(1):R22

Virginia Commonwealth University Reanimation Engineering Shock Center Laboratory, Department of Anesthesiology/Critical Care, Medical College of Virginia/Virginia Commonwealth University, 1200 East Broad Street, Richmond, VA 23298, USA.

Introduction: Acid-base abnormalities are common in the intensive care unit (ICU). Differences in outcome exist between respiratory and metabolic acidosis in similar pH ranges. Some forms of metabolic acidosis (for example, lactate) seem to have worse outcomes than others (for example, chloride). The relative incidence of each type of disorder is unknown. We therefore designed this study to determine the nature and clinical significance of metabolic acidosis in critically ill patients.

Methods: An observational, cohort study of critically ill patients was performed in a tertiary care hospital. Critically ill patients were selected on the clinical suspicion of the presence of lactic acidosis. The inpatient mortality of the entire group was 14%, with a length of stay in hospital of 12 days and a length of stay in the ICU of 5.8 days.

Results: We reviewed records of 9,799 patients admitted to the ICUs at our institution between 1 January 2001 and 30 June 2002. We selected a cohort in which clinicians caring for patients ordered a measurement of arterial lactate level. We excluded patients in which any necessary variable required to characterize an acid-base disorder was absent. A total of 851 patients (9% of ICU admissions) met our criteria. Of these, 548 patients (64%) had a metabolic acidosis (standard base excess < -2 mEq/l) and these patients had a 45% mortality, compared with 25% for those with no metabolic acidosis (p < 0.001). We then subclassified metabolic acidosis cases on the basis of the predominant anion present (lactate, chloride, or all other anions). The mortality rate was highest for lactic acidosis (56%); for strong ion gap (SIG) acidosis it was 39% and for hyperchloremic acidosis 29% (p < 0.001). A stepwise logistic regression model identified serum lactate, SIG, phosphate, and age as independent predictors of mortality.

Conclusion: In critically ill patients in which a measurement of lactate level was ordered, lactate and SIG were strong independent predictors of mortality when they were the major source of metabolic acidosis. Overall, patients with metabolic acidosis were nearly twice as likely to die as patients without metabolic acidosis.
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February 2006