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The Role of POCT in Emergency/

Intensive Care Patient

www.greatnetwork.org

Salvatore Di Somma, MD, PhD


Professor of Internal Medicine
Director Postgraduate School of Emergency
Medicine
Faculty od Medicine and Psicology,Sapienza
University of Rome Italy
Worldwide President GREAT -Network
Importance of early therapies in ER
as consequence of prompt diagnosis
• In 46,599 patients with ADHF (ADHERE)
• a delay in Treatment was associated with:

• 250% ↑ in acute mortality;


• 150% ↑ in Hospital length of stay

W.F. Peacock,S. Di Somma et al. Congest Heart Fail. 2008 14:17-20


Emergency Department Overcrowding

...“and hospitals have closed 198,000 beds .


With more patients needing care and fewer
resources to care for them, emergency
department crowding was inevitable.” .

Arthur L. Kellermann, M.D., M.P.H

Volume 355:1300-1303, 2006, Number 13


The “4 hours” decision time issue in ED
ED Overcrowding:Throughput related solutions
POINT OF CARE CONCEPT

BIOMARKERS
Imaging
Twanmoh J.R. et Al. . When overcrowding paralyzes an ED. Manag
Care 2006; 15 ( 6 ): 54-59
From “POC” to “Near to Patient” Blood gases

PRO

PRO
• Higher accuracy and precision
• Well-maintained instruments
• Highly trained laboratory professionals

CONTRA
• Transport delays
Reduce time to appropriate
• Sample queuing decisions making ,fabourably…
• Need to look up the results in the impacting patient outcome…
electronic medical
Global Trends in Point of Care Testing

Global Point-of-Care Testing (POCT) Market, M8FD-52Frost & Sullivan 2013


Differential diagnosis of Chest Pain in ED
Rule in or rule out?

Delayed ‘rule in’ Delayed ‘rule out

increases morbidity contributes to


and mortality, and overcrowding in the
may increase the risk ED, increasing
of complications patients’
associated with Acute uncertainty and
diseases, particularly anxiety, resulting in
in patients with pre a significant cost to
existing CAD the healthcare
system
ACS Diagnosis in ED

• ECG within 10 min.


after patients’s arrival

• TNs interpreted as a quantitative


variable :
the higher the level, the higher the likelihood
for the presence of MI

• NSTEMI is now a distinct entity from UA


• Rythm monitoring no more required for UA
. discharge allowed
0 -1 hour: Rapid ‘’Rule-out’’ and ‘’Rule-in’’

On market

Prototype

Cut-off levels and variations are assay specific


Use of absolute over relative changes
Use with clinical assessment and ECG
Obligation to retest 3-6 h in case of ongoing or recurrent Chest Pain
Diagnosis: caveats with hs -Tn

More accurate description of the ‘’false-positive’’ of hs - Tn


Diagnosis: caveats with hs -Tn
POCT Systems
Are POCT troponin’s dead?

• We now have hsTn


– “Lab tests are cheaper”
– “Lab test are more accurate”
– “The new hsTn central lab test is going to take
over!”

NOT SO FAST……………..
The BIG BOX in the basement

168 assays
vs 1 new
POC Cardio 3
vs Lab Singulex

Peacock WF.
Ann Lab Med 2016;36:405-412
HERE IT COMES: disposable troponin
assay
Differential Diagnosis of SOB
Symptoms of Congestion in AHF
BNP POCT – Studies at ED
• Milestone article on BNP as
biomarker

• Prospective multicenter, multi country,


study of 1586 patients presented to the ED
with acute dyspnea, in a 18-month period

• The present study addresses the diagnosis


of heart failure in a large, heterogeneous
population of patients in the acute care
setting.

• B-type natriuretic peptide


measured with a bedside
POCT immunoassay kit
NPs for Diagnosis of AHF
NPs +PCT for distinguishing S.O.B.

A. Maisel ,.Di Somma et al. Eur J Heart F 2012 mar;14(3)278-81


NPs Prognostıc value: discharge opportunity
after BNP decrease: The Italian RED study
1.0

0.8 -46.3%

-25.9%
0.6
Sensitivity

0.4

0.2
Probability of new cardiovascular
Percent change at 24h events or rehospitalitation
Percent change at discharge

0.0
0.0 0.2 0.4 0.6 0.8 1.0 Di Somma S. et al. Critical Care 2010
1 - Specificity
Cost-Effectiveness of BNP at ED:
The BASEL Study

$8000

$6000

$4000
€1,545 Savings/Patient
$2000
Fabourable effects
Biosite Triage BNP on approprıate rule out
(in pg/mL)
and hospıtal admıssıons and LOS
0
Muller C, et al. N Engl J Med. 2004;350:647-654.

Mueller C. NEJM 2007


Troponin related in-hospital mortality

,
67,924 ADHF patients

4240 (6.2%) positive for troponin


on admission

Mortality rate
Troponin positive cohort:
8.0%
Troponin negative cohort:
2.7%
CONFIDENTIAL
29

Adrenomedullin (ADM)
Key Regulator of the vascular system & Biomarker
of acute vascular dysfunction

1 Increase in plasma ADM =


Response of the body to
support vascular integrity
2 Interstitial ADM acts on
vascular smooth muscle
cells (VSMC) and
regulates vasodilation

1. Temmesfeld-Wollbrück et al. (2007) Thromb Haemost. 98(5):944-51.


2. Hirata et al. (1996) J Clin Endocrinol Metab. 81(4):1449-53.
3. Ishizaka et al. (1994) Biochem Biophys Res Commun. 200(1):642-6.
log(y) = 0.6344 + 0.4852 log(x)
R = 0.3764
Bio-Adrenomedullin in Acute Heart failure
Increased Mortality with Increasing Delays in
starting treatment in septic patients

hours

Kumar Crit .Care Med 2006


35

Acute vascular dysfunction in Sepsis


Sepsis:
 Overwhelming & life-threatening immune response to an infection
 Systemic inflammation leads to:
 loss of vascular integrity & vascular leakage
 systemic vasodilation
Consequences:
 Collapse of blood pressure (Septic shock)
 Reduced tissue perfusion & oxygenation
First-line Therapy:
 Vasopressors – to counteract vasodilation
 Fluids – to counteract vascular leakage

Unmet medical need: Prediction of shock


for early vasopressor therapy & close
monitoring of therapy success
CONFIDENTIAL
36

bio-ADM: Biomarker of Shock


validated in > 4,000 “real life” sepsis patients
FROG-ICU (ICU Sepsis+)1 Mebazaa (FR) multicentric (28) n = 2,078
ALBIOS (Sepsis & Septic Shock)1 Gattinoni (IT) multicentric (35) n = 956
AdrenOSS (Sepsis & Septic Shock)1 Mebazaa (FR) multicentric (24) n = 600
Sepsis in ED1 Melander (SWE) monocentric n = 300
Sepsis in ED2 Di Somma (IT) monocentric n = 101
Sepsis in ICU (Post-Surgical)3 Marx (GER) monocentric n = 56

Summary of results:
Diagnosis & Prediction of Shock
 bio-ADM is an early predictor of shock and vasopressor demand –
supporting early therapy
Monitoring of shock therapy & risk of mortality
 The dynamic nature of bio-ADM enables close monitoring of shock patients
1 manuscript in preparation or submitted 2 Caironi et al. CHEST [manuscript accepted]
3 Marino et al. Critical Care 2014, 18:R34.
4 Simon et al. Journal of Critical Care 2016, 38:68-72.
EPOC Application in Septic Patients
Accuracy of POCT for Urinary Infections
Creatinine caveats
Importance of Time in Acute Kidney Injury:
we need AKI biomarkers !

In ACS Time is Myocardium !!


And we have troponin…
IN AKI Time is important to stop the
progression of nephrons loss ? ?
We need AKI biomarker like
troponin….
log(y) = 2.6319 + -0.008305 x
R = 0.7339
Diagnostic and short-term prognostic utility of plasma Pro-Enkephalin (pro-ENK) for Acute Kidney Injury
in patients admitted with sepsis in the Emergency Department

pro-ENK: normals < 80 pmol/L NGAL: normals < 0.1 µg/mL

 pro-ENK: Majority of patients without kidney failure are within normal range, despite inflammation.

 NGAL: elevated above normal range for almost all patients.


Marino R. Di Somma S. et al JNEP 2014
TIMP2 IGFBP7
Functional and Damage Kidney Biomarkers

Penkid
What about TBI

• Biomarker physiology
– Is the brain different?
– Can the marker get out?
– Is the timing like the heart?

• Is CT YES/NO the right endpoint?

• Is functional testing a better biomarker?


C Statistic
Is blood the only answer?

• What about saliva?

• Saliva
– Similar to blood
– Lots of WBC
– Lots of bacteria
Spit for TBI

• N=106 saliva samples from mTBI patients


• N=48 healthy controls.
• Explored 100 biomarkers by quantitative immunoassays
– ROC curve analysis determined TBI diagnostic accuracy
– 10 biomarkers selected as ≥80% TBI diagnostic accuracy
Stroke Challenges
• Dx required for treatment
– ~750k CVA per year in US
– ~250k NEVER have a cause determined
– No dx = No tx (guidelines say ASA and good luck)

• Dx by assumption…… does this even make sense?


– All AF must have embolic strokes?
• 75 year old male with large left CVA, known to have PAF… is it
AF?
– In the absence of AF or a lacune, is it always atherogenic?
Microarray

• 500k
proteins on
1 chip
Microarray technology

• Used to measure genome wide expression of genes


• Typically a glass slide to which DNA molecules are
fixed in an orderly manner at specific locations
– called spots or features

• May contain thousands of spots and each spot may


contain a few million copies of identical DNA
molecules that uniquely correspond to a gene
Sant’Andrea Emergency –Medicine:
Research Group