Anne-Maree KellyProfessor and DirectorJoseph Epstein Centre for Emergency Medicine Research @Western Health

I received financial support for travel and accommodation from Radiometer Pty Ltd to present a similar presentation at 4th International Symposium on Blood Gas and Critical Care in France in 2008.

I am undertaking some research with A/Prof Rees into calculated values which may be commercialised. I have no pecuniary interest in this program.

I have not received industry funding for any of my blood gas research projects.

To share a research journey

To describe how venous blood gas analysis might fit into clinical care of selected patients

An emergency physician, an educator and a clinical researcher

My research journey started when a ‘rep’ came to the ED with a transcutaneous CO2 monitor and I wanted to know if it worked in an ED population.

My questions come from my clinical practice – with a focus on working smarter for better patient outcomes

Venous blood gases is one of my research streams

How we work

Clinical focus: ED, prehospital care and related

Small team◦ Myself◦ Research nurse◦ Registrars, students

Collaborative approach

Pain management in ED Acute respiratory disease: asthma, COPD and

pneumothorax Estimating children’s weight in emergencies Intranasal naloxone for heroin overdose Acute cardiology and resuscitation, especially

chest pain in ED Clinical decision rules Implementation science and EBM

2001: Accuracy of pulse oximeters in resp. disease 2001: Arteriovenous pH agreement 2002: Venous pH and pCO2 as screening tests for

hypercarbia (derivation) 2004: Agreement for K+, bicarbonate 2005: Validation screening VBG for hypercarbia 2006: ICU studies 2011-13: Meta-analyses and systematic reviews 2012-13: Arteriovenous agreement and clinical utility in

patients undergoing NIV 2013: External validation of mathematical prediction

model (in collaboration with Aalborg University, Denmark)

Year Patient population

Paper

2001 General ED population Kelly AM, McAlpine R, Kyle E. Venous pH can safely replace arterial pH in the initial evaluation of patients in the emergency department. Emerg Med J 2001; 18:340-2

2002 Acute respiratory disease Kelly AM, Kyle E, McAlpine R. Venous pH and pCO2 can be used to screen for significant hypercarbia in emergency patients with acute respiratory disease. J Emerg Med 2002; 15-19.

2004 General ED population Fu P, Douros G, Kelly AM. Does potassium concentration measured on blood gas analysis agree with serum potassium in patients with diabetic ketoacidosis? Emerg Med Austral 2004; 16:280-3.

2004 General ED population Kelly AM, McAlpine R, Kyle E. Agreement between bicarbonate measured on arterial and venous blood gases. Emerg Med Australas 2004; 16:407-9.

2005 COAD Kelly AM, Kerr D, Middleton P. Validation of venous pCO2 to screen for arterial hypercarbia in patients with chronic obstructive airways disease. J Emerg Med 2005; 28;4:377-9.

2006 ICU Middleton P, Kelly AM, Brown J, Robertson M. Agreement Between Arterial And Venous Values For pH, Bicarbonate, Base Excess and Lactate Emerg Med J 2006; 23:622-4.

2010 COAD Lim BL, Kelly AM. A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department. Eur J Emerg Med 2010; 17:246-8.

2010 General ED population Lim BL, Kelly AM. How useful is transcutaneous carbon dioxide monitoring in the adult emergency department? Hong Kong J Emerg Med 2010; 17:82-4

2011 NIV Kelly AM, Klim S. Agreement between arterial and transcutaneous pCO2 in patients undergoing non-invasive ventilation Respir Med 2011;105:226-9.

2013 NIV Kelly A, Klim S. Agreement between arterial and venous pH and pCO2 in patients undergoing non-invasive ventilation in the emergency department Emerg Med Australas [at press]

2013 NIV Agreement Between Mathematically Arterialized Venous vs. Arterial Blood Gas Values in Patients Undergoing Non-invasive Ventilation [submitted]

2013 NIV Can trend of pH and pCO2 be used to monitor progress in patient undergoing non-invasive ventilation? A prospective cohort study

Establishing acid-base status◦ Mainly pH; but also bicarbonate

Measuring respiratory function/ ventilation Mainly pCO2; but also pH

‘Quick check’ potassium, haematocrit, some electrolytes◦ Not addressed in this presentation

Less pain for patients Fewer complications, especially vascular and

infection Fewer needle-stick injuries Easier blood draw Minimal training requirement

JANE TRAN

◦ 26 year old, insulin dependent diabetic

◦ 2 days of vomiting and diarrhoea.

◦ Pulse 120 bpm, BP 100/60, bedside glucose ‘hi’

◦ 74 year old COAD◦ Acute respiratory

distress. ◦ Pulse 110, BP 140/-,

oxygen saturation (on air) 88%

Can we ◦ Exclude / diagnose◦ Monitor progress of◦ Base therapeutic decisions for

Metabolic acidosis or acute respiratory failure using venous blood gas analysis rather than arterial?

Outcome of interest is how closely venous and arterial values agree, not how well they correlate

Weighted mean difference gives an estimate of the accuracy between the methods

95% limits of agreement give information about precision

Arterial value

Venous value

95% LoA

There is limited data about the tolerance clinicians have with respect to agreement between arterial and venous values of blood gas parameters

Depending on this tolerance, the degree of agreement may be acceptable or unacceptable

This is included in a University of Melbourne Scholarly Selective project late 2013

Patient cohorts in the published literature are highly varied

Patient groups of interest are those at high risk of acidosis or hypercarbia◦ Reporting does not always report this detail◦ Data may to be dominated by patients with normal pH,

pCO2 and blood pressure

◦ Need for research focussed on high risk patient groups

13 studies◦ Range from 44 to 346 patients; Several JECEMR

Various conditions◦ DKA (3), COAD (4), trauma (1)

2009 patients

Weighted mean difference of 0.033 pH units

95% limits of agreement (7 studies) generally within +/- 0.1 pH units

DKA COAD

◦ 3 studies (265 patients)

◦ Weighted mean difference = 0.02 pH units

◦ 95% limits of agreement = -0.009 to 0.02 pH units (1 study)

◦ 5 studies (643 patients)

◦ Weighted mean difference= 0.034 pH units

◦ 95% limits of agreement generally +/- 0.1 pH units (3 studies)

One ICU-based study suggests that as hypotension increases, AV pH agreement deteriorates◦ Very small patient numbers◦ Finding not yet validated

University of Melbourne scholarly selective 2013◦ Arteriovenous blood gas agreement in varying

levels of shock and cardiac output

We know:◦ Generally close AV agreement in both respiratory and

metabolic disease

Evidence gaps:◦ AV agreement in various levels and types of shock◦ AV difference in toxicology scenarios (1 small study in

TCA OD only)◦ AV difference in mixed acid-base disease

8 studies

965 patients

Various conditions (COAD 4)

Weighted mean difference = 6.2 mmHg

95% limits of agreement: up to -17.4 to +23.9 mmHg◦ 5/7 studies reporting LoA report LoA band >20mmHg

4 studies

452 patients

Weighted man difference = 7.26 mmHg

95% limits of agreement: up to -14 to +26 mmHg◦ All 3 studies that reported LoA report LoA band

>20mmHg

Author, year No. Screening cut-off

Sens. Spec. NPV %ABG avoided

Kelly, 2002 196 45 100 57 100 43

Kelly, 2005 107 45 100 47 100 29

Ak, 2006 132 45 100 * 100 33

McCanny, 2011

94 45 100 34 100 23

POOLED DATA

529

45 100 (95% CI 97-100)

53(95% CI 57-58)

100(95% CI 97-100)

35%(95% CI 32-41)

Data limited to studies in cohorts with respiratory disease

Data recently submitted for publication

47 comparisons in 34 patients

Average arteriovenous difference for change in pH (v-a) was 0.001pH units (LoA -0.7 to +0.7).

Average arteriovenous difference between change in pCO2 (v-a) was 0.04mmHg (LoA -17.3 to +18.2).

For both pH and pCO2, in the majority of cases the direction of change was the same although the magnitude was variable.

We know: AV agreement is NOT good enough for clinical inter-

changeability Wide limits of agreement

Venous pCO2 has utility as a screening test for hypercarbia Excellent NPV

Evidence gaps: Whether trend in venous pCO2 and pH can safely drive a care pathway

for COAD Subject of current international research project (JECEMR is a partner)

8 studies

1211 patients

Various conditions (COAD 2)

Weighted mean difference = -1.3mmol/l

95% limits of agreement : up to +/- 5mmol/l (3 studies)

Two studies only

Data not suitable for pooling

JANE TRAN

◦DKA

◦ AV agreement is acceptable; at least in non-shocked patients

◦ Can use venous pH to diagnose/ monitor

◦ Acute respiratory distress

◦ pH agreement good but pCO2 has considerable imprecision

◦ Can use venous pCO2 as a screening test for hypercarbia

◦ ? Can monitor trend*

Team from Center for Model Based Medical Decision Support Systems, Dept of Health Science and Technology, Aalborg University, Denmark (A/Prof Steven Rees)

Developed venous to arterial conversion method using venous blood gas variables and pulse oximetry

Designed to be incorporated into blood gas analysers

The method calculates arterial values using mathematical models

Assumes:◦ Constant value of the

respiratory quotient of 0.82◦ Change in base excess

from arterial to venous blood is 0 mmol/l

Rees SE, Toftegaard M, Andreassen S. A method for calculation of arterial acid–base and blood gas status from measurements in the peripheral venous blood. Comp Methods Programs Biomed. 2006, Vol 81, 18-25.

Respiratory patients◦ Arterial-calculated pH difference = -0.001pH units (95% LoA -

0.026 to +0.026)◦ Arterial-calculated pCO2 difference = -0.68mmHg (95% LoA -

4.81 to +3.45 mmHg)

ICU◦ Arterial-calculated pH difference = -0.002pH units (95% LoA -

0.029 to +0.025)◦ Arterial-calculated pCO2 difference = 0.3mmHg (95% LoA -3.58

to +4.18 mmHg)

ED◦ pH can be calculated to within 0.02 pH units (95% LoA)◦ pCO2 can be calculated to within 4mmHg (0.5kPa)

82 sample-pairs (60 patients)

Mean difference for arterial pH (actual-calculated) was 0.01 pH units (95% limits of agreement: -0.04, 0.06).

Mean difference for pCO2 (actual-calculated) was -0.45mmHg (95% limits of agreement: -10, +9).

pH and bicarbonate◦ Probably close enough agreement for clinical purposes

in DKA, acute respiratory failure, isolated metabolic acidosis

◦ More work needed in toxicology, shock, mixed disease

◦ Scholarly selective addressing agreement in shock and with varying levels of cardiac output

pCO2◦ NOT enough agreement for clinical purposes, either as one-off

or to monitor change

◦ Data suggests venous pCO2 is useful as a screening test

Base excess◦ Probably not enough agreement for clinical purposes

Mathematical modelling approaches might be more accurate especially for pCO2

For broad applicability an app/ similar would be more feasible than integration into blood gas machines

More work needed to prove accuracy and precision in high risk groups

JECEMR has led research into arteriovenous blood gas agreement

Our >10 year journey has steadily added pieces to build understanding of agreement in different disease states

The accumulated data has changed practice both ‘home’ and ‘away’

Questions?

Questions?

Questions?

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@kellyam_jec

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