This presentation discusses the state of evidence for arteriovenous blood gas agreement for pH, pCO2, bicarbonate and base excess and how that fits into clinical decision-making. It also describes the resaerch journey of a smal clinical team to answer important clinical questions and address an issue of concern to patients.

1. Anne-Maree Kelly
Professor and Director
Joseph Epstein Centre for Emergency Medicine
Research @Western Health

2.  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.

3.  To share a research journey
 To describe how venous blood gas analysis might
fit into clinical care of selected patients

4.  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

5. How we work
 Clinical focus: ED,
prehospital care and
related
 Small team
◦ Myself
◦ Research nurse
◦ Registrars, students
 Collaborative
approach

6.  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

7.  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)

8. 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

9.  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

10.  Less pain for patients
 Fewer complications, especially vascular and
infection
 Fewer needle-stick injuries
 Easier blood draw
 Minimal training requirement

11. 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%

12.  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?

13.  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

14.  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

15.  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

16.  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

17. 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)

18.  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

19.  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

20.  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

21.  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

22. 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
52
9
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

23.  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.

25.  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)

26.  8 studies
 1211 patients
 Various conditions (COAD 2)
 Weighted mean difference = -1.3mmol/l
 95% limits of agreement : up to +/- 5mmol/l
(3 studies)

27.  Two studies only
 Data not suitable for pooling

28. 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*

29.  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

30.  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.

31.  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)

32.  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).

33.  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

34.  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

35.  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

36.  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’

37. Questions?
Questions?
Questions?
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