Kollef - Moving the ICU to the ED€¦ · Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis -The HYPRESS Trial Venkatesh B, et al. N Engl J Med 2018;

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Moving the ICU to the ED to Improve Patient Outcomes: Focus on ARDS,

Sepsis and PEMarin H. Kollef, MD

Professor of Medicine

Virginia E. and Sam J. Golman Chair in

Respiratory Intensive Care Medicine

Washington University School of Medicine

St. Louis, Missouri

Conflicts of Interest

Academy of Infection ManagementAllerganAridisMerckShinogi

Timing is Crucial in the ED! - Do not Delay Fluids/Antibiotics/Pressors/Optimal Vent Settings

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Background: Mechanical Ventilation in the ED

Easter B, Fischer C, Fisher J. Amer J Em Med. 2012;30:1183-1188

Common: 300,000 annually

Deadly: 25% mortality

Pulmonary complications: high

incidenceFuller BM, et al. Acad Emerg Med 2013. Fuller BM, et al. Chest 2015.Dettmer MR, et al. J Crit Care 2015.Mikkelsen ME, et al. Shock 2013.

IMPROVE Study Group. N Engl J Med 2013; 369: 428-43 7.

Neto AS, Cardoso SO, et al. JAMA 2012;308(16):1651-1659

Lung-Protective Ventilation in At-Risk Patients

Preliminary Data- Lung Protection Uncommon

Fuller BM, Mohr NM , Dettmer M. Acad Emerg Med. 201 3 ; 20: 659-669.

Fuller BM, et al. CHEST 2015; 148(2): 365-374.

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Study Objectives

Evaluate the effectiveness of an ED-based lung-protective mechanical ventilation protocol on reducing the incidence of pulmonary complications including progression to ARDS

Design and SubjectsSingle-center, quasi-experimental before (2009-2013) - after (2015-2016) study

Population: mechanically ventilated adult ED patients

Primary Outcome: ARDS + VAC

Design

n=1,192 n=513

Fuller BM, et al. BMJ Open 2016; 6e010991.

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Fuller BM, et al. Ann Emerg Med. 2017;70:406-418.

Pre-intervention

Group (n= 1,192)

Intervention

Group (n= 513)

P value

Age (yr) 60.4 (21.1) 58.0 (24.0) <0.001

Male, n (%) 628 (52.7) 303 (59.0) 0.02

Caucasian

African-American

Other

478 (40.1)

698 (58.6)

16 (1.3)

232 (45.2)

280 (54.6)

1 (0.2)

0.05

0.13

0.03

Comorbidities, n (%)

Diabetes

Cirrhosis

CHF

Dialysis

COPD

Immunosuppression

Alcohol abuse

HIV/AIDS

427 (35.8)

84 (7.0)

289 (24.2)

95 (8.0)

304 (25.5)

95 (8.0)

177 (14.8)

29 (2.4)

166 (32.4)

41 (8.0)

115 (22.4)

43 (8.4)

122 (23.8)

66 (12.9)

76 (14.8)

6 (1.2)

0.17

0.49

0.31

0.77

0.45

0.01

0.99

0.09

Height (in) 67.1 (4.1) 67.9 (3.9) <0.001

Weight (kg) 84.7 (30.6) 83.9 (26.5) 0.68

BMI 29.3 (10.7) 28.2 (8.8) 0.07

Temperature (Celsius) 36.9 (1.1) 36.5 (1.2) <0.001

Mean arterial pressure 87.3 (22.5) 84.0 (41.6) 0.34

Lactate 2.2 (1.4-3.9) 3.0 (1.6-5.2) <0.001

APACHE II* 14.0 (8.0) 17.0 (13.0) <0.001


Results- Ventilator Settings


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Results- Tidal Volume


Results- Clinical Outcomes


Results- Clinical OutcomesPropensity-

matched


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Baseline characteristics Preintervention (n= 186) Intervention Group (n= 43) P value

Age (yr) 57.7 (50.9-71.9) 57.5 (43.5-66.3) 0.14

Male, n (%) 106 (57.0) 28 (65.1) 0.33

Race, n (%)

Caucasian

African-American

Other

97 (52.2)

86 (46.2)

3 (1.6)

22 (51.2)

22 (51.2)

0 (0.0)

0.91

0.56

0.40

BMI 29.9 (11.0) 30.5 (13.4) 0.30

MAP 79.3 (20.9) 75.0 (36.0) 0.30

Lactate 3.0 (1.9-6.0) 4.7 (2.3-7.9) 0.06

APACHE II 17.1 (5.5) 23.7 (7.8) <0.01

SOFA 6.0 (4-8) 8.0 (4-9) 0.02

Reason for mechanical ventilation, n (%)

Medical

Trauma

Other

129 (69.4)

20 (10.8)

37 (19.9)

33 (83.7)

5 (11.6)

5 (11.6)

0.34

0.87

0.21

Sepsis, n (%) 101 (54.3) 30 (69.7) 0.17

Intravenous fluids in ED (liters) 2.5 (2.0) 1.7 (1.6) 0.15

Blood products, n (%) 33 (17.7) 10 (23.3) 0.40

Central venous catheter, n (%) 89 (47.8) 22 (51.2) 0.70

Antibiotics, n (%) 96 (51.6) 29 (67.4) 0.11

Vasopressor infusion, n (%) 69 (37.1) 24 (55.8) 0.02

Fuller BM, et al. Crit Care Med 2017;45:645-652.

Fuller BM, et al. Crit Care Med 2017;45:645-652.

Pre-Intervention

group (n= 186)

Intervention group (n= 43)

Adjusted Odds Ratio or Between-Group Difference

(95% CI)

P value

Mortality, n(%) 102 (54.8)

17 (39.5)

0.38 (0.17 - 0.83)

0.02

Secondary outcomes (days)Ventilator-freeICU-freeHospital-free

7.7 (9.9)7.2 (9.4)4.0 (6.3)

11.6 (10.8)9.1 (9.2)5.7 (7.7)

0.010.180.13

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Septic shock: persisting hypotension; requiring vasopressors to maintain MAP ≥65 mm Hg; lactate level >2 mmol/L despite adequate volumes

Singer M, et a. JAMA 2016;315:801-810.

Shankar-Hari M, et al. JAMA 2016;315:775-87.

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Increased Mortality With Inadequate Antibiotic Therapy in Infections Requiring ICU Admission

ICU=intensive care unit.

Site of infection includes bloodstream, lung, wound, gastrointestinal tract, urinary tract, and miscellaneous (includes peritoneal infection, meningitis, endocarditis, and infections of the skin and fascia).

Kollef MH. Chest 1999;115:462-474.

Hosp

ital M

ort

ality

(%

)

0

10

20

30

40

60

All Cause

P<.001

Infection Related

P<.001

Mortality Type

Inadequate antimicrobial treatment

Adequate antimicrobial treatment

5052%

24%

42%

18%

655 (32.8%) infected169 (25.8%) inappropriate treatmentN = 2000

Park SY, et al. Int J Antimicrob Agents 2018; doi:10. 1016/j.ijantimicag.2017.10.018

• 146 patients with CRABC bacteraemic pneumonia

• 128 (87.7%) patients were treated in the ICU

• 110 (75.3%) had VAP

• 42 (28.8%) received appropriate empirical therapy

Liu VX, et al. AJRCCM 2017;196:856-863.35,000 randomly selected sepsis inpatients 21 emergency depart ments 2010-2013 Northern CA.

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In multivariable model, each hour of time to complete 3-hour bundle a/w

higher mortality

(OR, 1.04; 95%CI, 1.02 to 1.05; P<0.001)

Seymour CW, et al. NEJM 2017; 376:2235-2244.

Alam N, et al. Lancet Respir Med 2018;6:40-50.

• Ceftriaxone 2 g vs. Placebo in ambulance• Netherlands• 75% of bacteria staph, strep, E. coli

JAMA. 2014;311(13):1308-1316.

Mortality Severe Sepsis and Septic Shock in Australia and New Zealand, 2000-2012

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Rivers E et al. N Engl J Med 2001;345:1368-1377.

Rivers E et al. N Engl J Med 2001;345:1368-1377.

Standard Therapy EGDTMortality: 46.5% 30.5%

P = 0.009

The PRISM Investigators. N Engl J Med 2017;376:2223-2234.

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The PRISM Investigators. N Engl J Med 2017;376:2223-2234.

EGDT Cont EGDT Cont EGDT Cont EGDT ContLactate 7.7 6.9 4.8 5.0 6.7 6.6 7.0 6.8ScvO2 48.6% 49.2% - - 76% - 74% -

Death 30.5% 45.5% 21% 18.9% 18.6% 18.8% 29.5% 29.2%

Rivers PROCESS ARISE ProMISe

Are The Patients the Same?

NO!

Holst LB et al. N Engl J Med 2014;371:1381-1391.

Blood Hemoglobin Levels in Patients in the ICU at Baseline and after Randomization

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Time to Death and Relative Risk of Death at 90 Days

Holst LB et al. N Engl J Med 2014;371:1381-1391.

Caironi P et al. N Engl J Med 2014;370:1412-1421.

Albumin through D 28 and Net Fluid through D 7

Caironi P et al. N Engl J Med 2014;370:1412-1421.

Probability Survival from Randomization through Day 90

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Asfar P et al. N Engl J Med 2014;370:1583-1593.

MAP during the 5-Day Study Period

De Backer D et al. N Engl J Med 2010;362:779-789.

Norepinephrine Shortage US Hospitals 2011

Vail E, et al. JAMA 2017 Apr 11;317(14):1433-1442.

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Early Vasopressin v Norepinephrine: Kidney Failure in Septic Shock

Gordon AC, et al. JAMA. 2016;316:509-518.

Khanna A et al. N Engl J Med 2017. DOI: 10.1056/NEJMoa1704154

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Khanna A et al. N Engl J Med 2017. DOI: 10.1056/NEJMoa1704154

Volbeda M et al. Intensive Care Med 2015;41:1220-123 4.

CortocosteroidsIn Septic Shock

CHEST 2016 149, 209-219DOI: (10.1378/chest.15-1733)

Corticosteroids Severe CAP

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JAMA. 2016;316(17):1775-1785. doi:10.1001/jama.2016.14799

JAMA 2016;316(17):1775-1785

Continuous infusion 200 mg HCT 5 d followed by dose tapering until d 11

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis -The HYPRESS Trial

Venkatesh B, et al. N Engl J Med 2018; 378:797-808. Annane D, et al. N Engl J Med 2018; 378:809-81 8.

Hydrocortisone 50-mg IV q 6 hours/fludrocortisone 5 0-µg poContinuous infusion hydrocortisone 200 mg per day

Adjunctive Corticosteroids for Septic Shock

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Mean Daily Fluid Balance

Mil

lili

ters

Day

†

†

†

†

†

*†

*†

*†* *

Survivors

Nonsurvivors

Murphy CV et al. Chest 2009;136:102-109.

Cumulative Daily Fluid Balance

Mil

lili

ters

Day

††

†

†

*† * **

*

Nonsurvivors

Survivors


Optimizing the Ebb and Flow Phases

Adequate Fluid Resuscitation

Conservative Fluid Management

+

+

-

+

+

-

-

-

n=93 n=31 n=53 n=35

P < 0.001


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Zambia: 6-hour sepsis protocol emphasizing IVFs, va sopressors, and RBCs in the ED for patients with septic shock

Andrews B, et al. JAMA 2017;318:1233-1240.

Shackelford SA, et al. JAMA 2017 Oct 24;318:1581-15 91.

Hoste EA, et al. British Journal of Anaesthesia 201 4;113: 740–747.

Four Phases of Intravenous Fluid Therapy

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Traditional Methods for Detection of BSI

Gram Stain

18 – 24 h

Hours to Days

Subculture

Organism identification

and susceptibility

testing

Traditional Methods for Detection of BSI

Accurate but slow!

Ideal Diagnostic Tool for Sepsis

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Vazquez C, Kollef MH. Clin Infect Dis 2018.

Acinetobacter spp.

EET = effective empiric therapyIET = ineffective empiric therapyRDDT = rapid diagnostic directed treatment

Douglas I. Curr Opin Infect Dis 2016;29:197-204.

Timing of Microbiologic Diagnostics

BiofireCuretis

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PERTPE Response Team

Rodriguez-Lopez J, et al. Semin Respir Crit Care Med 2017;38:51-55.

Rodriguez-Lopez J, et al. Semin Respir Crit Care Med 2017;38:51-55.

Mean 9.22 6.31 6.86 4.4 12,219 16,843 13.38 15.07

SD 16.09 7.44 9.35 5.05 20,957 25,242

Pvalue

.004 .006 .12 .72

Control PERT Control PERT Control PERT Control PERT

Hospital LOS ICU LOS Direct Cost Mort ality

Xenos ES, et al. J Vasc Surg 2018;67:e13-e14.

U Kentucky Lexington PERT Experience

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Thank you!

Documents

Kollef - Moving the ICU to the ED€¦ · Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis -The HYPRESS Trial Venkatesh B, et al. N Engl J Med 2018;