Critical Care Testing - Quality Assurance

3
3
Quality Assurance
Critical Care Testing
Quality Assurance
This book describes the various quality assurance
procedures at all stages in the patient testing
cycle and how they contribute towards obtaining
the correct patient result.
www.roche.com/poc
Roche Diagnostics GmbH

Roche Near Patient Testing
D-68298 Mannheim
4.01-3190285
Germany
ISBN 3-88630-250-4
Quality Assurance
Andrew St John
Roche Diagnostics
1
Impressum
© by Roche Diagnostics, Mannheim, Germany
Cover: !Now Werbeagentur AG, CH-4051 Basel
Artwork & Layout: Eva Baumgartner, CH-8200 Schaffhausen
Printed by: stamm+co, CH-8226 Schleitheim
First Edition April 2001
Preface Quality Assurance & Critical Care Testing
Preface
This book provides an overview of quality assurance as applied

to the critical care testing process and it is intended for a broad
audience. First and foremost that audience includes those peo-
ple who have received no formal training in laboratory practices
such as clinicians, nurses and paramedical staff but who are
now using diagnostic devices.
While laboratory professionals almost live and breathe quality

assurance, the topics of pre-analytical and post analytical qua-
lity assurance have not perhaps received the attention they
deserve in the past but are especially important to the critical
care testing process. Therefore I would hope that my scientific
colleagues will also find new and relevant information in this
booklet. Last but by no means least I would encourage my com-
pany colleagues to use this book to help them provide some of
the answers to the growing number of questions that custo-
mers now direct to the suppliers of diagnostic devices, many of
which are related to issues of quality.
As with the previous books many people, both colleagues and

customers, have made contributions to this book. First and fore-
most, my appreciation goes to Dr Jean-Francois Mollard, for-
merly of AVL France and Dr Sharon Ehrmeyer of the University
of Wisconsin, USA whose previous publications in the area of
quality assurance I have drawn on extensively for this book.
My thanks also to Miles Sykes of the Bradford Royal Infirmary,

UK for his critical comments and to my usual prooof-readers,
Les Watkinson of Roche Australia and Regina Herz from Roche
Diagnostics, Graz. Finally of course, I must acknowledge Eva
Baumgartner who as with the previous books has converted my
writing into the professional publication that you have in front
of you today.
Dr. Phd. Andrew St John

Roche Diagnostics, Mannheim, Germany
3
Quality Assurance & Critical Care Testing Contents
Contents:
Chapter I
Introduction 1
Quality assurance & the critical care testing cycle
Chapter II
Pre-Analytical Quality Assurance 11
Steps in pre-analytical quality assurance
Collection device or container
Anticoagulants
Patient preparation
Sample site
Sample collection
Sample treatment and transport
Immediate pre-analysis
Summary of pre-analytical quality assurance procedures
Chapter III
Analytical Quality Assurance 41
Aspects of analytical quality assurance
Terminology, types & principles of quality control
Internal quality control using control materials
Internal quality control using patient data
Special aspects of internal quality control
on Roche instruments
External quality control using control materials
Factors affecting analytical quality
Contents Quality Assurance & Critical Care Testing
Chapter IV
Post-Analytical Quality Assurance 83
Stages in post-analytical quality assurance
Combining results with patient information
Critical or panic values
Interpretation of data
Reporting of data and information
Chapter V
Management of testing
outside the laboratory 97
Professional & local guidelines
References 102
List of figures & tables 106
Index 109
5
Quality Assurance & Critical Care Testing Chapter I
6
Chapter I Quality Assurance & Critical Care Testing
Chapter I
Introduction
1
Quality and Critical Care Testing
There are many definitions of quality but in relation to dia-

gnostic testing a quality service can be defined as one which
meets the needs and expectations of the users (doctors &
nurses) or customers (patients).
In plain terms this means providing the right result accom-

panied by the right interpretation for the right test at the
right time on the right specimen from the right patient.
As part of the evolution of quality systems in healthcare

many laboratories have adopted the principles of Total Qua-
lity Management (TQM) which is a structured approach to
meeting quality standards. TQM as shown in the diagram
opposite is a feedback cycle which comprises a number of
distinct processes called Quality Planning, Quality Labora-
tory Processes, Quality Control, Quality Assurance and
lastly Quality Improvement.
In order to provide a concise account of the quality proces-

ses and potential errors in critical care testing this book will
concentrate on the Quality Assurance and Quality Control
aspects. For more details of the principles of TQM, readers
should consult a laboratory textbook such as Tietz (1).
Quality Assurance (QA) can be defined as the management

process by which the quality of the complete testing pro-
cess is both maintained and improved.
Quality Control (QC) is just one part of QA and is concerned

with analytical quality ie obtaining the right result.
2
Quality in Critical Care Testing
Quality
Planning
Quality TQM Quality

Improvement Laboratory
processes Processes
in
Critical
Care Testing
Quality Quality
Assurance Control
3
Quality Assurance and Critical Care Testing
The critical care testing process or patient testing cycle

commences by the clinician asking a question about the
patient which is answered by performing a laboratory ana-
lysis and providing a diagnostic answer.
A simple approach to assessing and improving the quality of

critical care testing is to consider the testing cycle in three
phases as shown in the diagram opposite.
The first pre-analytical stage of the cycle involves collection

and transport of the patient specimen. Although the move-
ment of critical care testing closer to the patient has redu-
ced the potential length of the pre-analytical phase, the labi-
lity of many critical care parameters still means that pre-
analytical procedures are especially important to monitor
and control.
The second phase is the actual analysis of the specimen.

This analytical phase requires conventional quality control
procedures such as internal and external quality control
which are similar to those for any analytical device.
The third and final phase is called the post-analytical phase

and involves processes such as integration of patient infor-
mation with analytical results, comparison to reference and
critical values, interpretation and finally the reporting of
information – the diagnostic answer – to the clinician and
into the patient record.
4
Quality Assurance & Critical Care Testing

Diagnostic answer ! Clinical question ?
Reporting of Patient Specimen

Information Collection
Patient
Post-Analysis Testing Pre-Analysis
Cycle
Adding Value Specimen

to Data Analysis Transport
Quality Control
5
Potential Errors in Critical Care Testing
The consequences of not delivering a quality critical care

testing service are many but they include:
• Making the wrong diagnosis in a patient
• Patients receiving the wrong treatment
• Patients not receiving treatment or receiving it at the

wrong time
• Conducting the wrong investigations in a patient
Poor quality is often due to errors occurring in the critical

care testing process and the diagram opposite shows the
major errors associated with each of the 3 phases which
make up the patient testing cycle.
The fact that more errors are associated with the pre-analy-
tical phase is primarily a reflection of the fact that more
manual interventions are required compared to the other
two phases where a degree of automation exits.
Ideally each laboratory should conduct a systems analysis of

its testing process to document all the processes and iden-
tify all the potential errors which may occur. Quality assu-
rance procedures are then designed to prevent or minimise
these errors.
More details of the potential errors in each phase of the cri-

tical care testing cycle are described in the following sec-
tions of the booklet.
6
Major Potential Errors in Critical Care Testing
Patient
Patient
Post-Analysis Testing Cycle Pre-Analysis
• Result not reported

Analysis • Incorrect container
or report delayed • No or wrong
• Transcription error anticoagulant
in written report • Instrument not • Wrong patient or
• No clinical details calibrated correctly wrong identification
with result • Insufficient sample • Excessive delay
• Critical value not • Unstable precision before analysis
highlighted of instrument
• Interfering
substances present
7
Key Aspects of Quality Management
There are a number of important aspects of quality mana-

gement which apply universally to all parts of the critical
care testing cycle.
Documentation
The involvement of many different people in critical care
testing demands that all procedures are documented in step
by step, easy to understand fashion. Guidelines for what
should be contained in such documents are available from
accreditation bodies and the NCCLS. Some laboratories
have adopted the term Standard Operating Procedure (SOP)
for such documents. They should be reviewed regularly and
revised whenever changes are implemented.
Training and Education

Training and education assumes even greater importance
when testing involves personnel who are not trained labo-
ratory professionals. Training needs to be monitored so that
new staff are incorporated into the program and the pro-
gram should be revised as procedures change in response
to the need for quality improvement or the development of
new services.
Audit and Accreditation

Several countries now have fully accredited laboratory servi-
ces where all laboratories are regularly inspected by an exter-
nal agency and granted a license to carry out diagnostic tests.
Even in those countries where accreditation is not yet esta-

blished, audit procedures should exist which allow internal
and external staff to regularly review diagnostic services.
Such a review process should also occur when service pro-
blems are identified and need to be resolved as part of the
quality planning and improvement process.
8
Key Aspects of Quality Management
Docu- Training/ Audit/

mentation Education Accreditation
All processes All staff carrying All processes

associated with out critical care associated with
critical care testing should critical care
testing should receive regular testing should
be documented training and be reviewed by
education service users
or external
bodies
9
10
Chapter II Pre-Analytical Quality Assurance
Chapter I I
Pre-Analytical
Quality Assurance
11
Pre-Analytical Quality Assurance Chapter II
Steps in Pre-Analytical Quality Assurance
The pre-analytical phase of critical care testing starts with

the request to perform an analysis and finishes with the
introduction of the specimen into the analyser.
The diagram opposite shows that several distinct stages

exist in the pre-analytical process where errors can occur
that will affect the patient result and this may lead to misin-
terpretation and incorrect treatment.
While the development of testing nearer the patient has

reduced the time taken to transport specimens to the instru-
ment, there remain several manual steps where there is the
potential for significant errors to occur. Thus pre-analytical
variation in critical care parameters is often greater than ana-
lytical variation.
The aim of pre-analytical quality assurance is to remove or

minimise these sources of variation or error. A quality assu-
rance programme should involve the following processes:
i. Documentation of step by step procedures.

ii. Training and supervision of all people involved in
pre-analytical procedures.
iii. Monitoring important pre-analytical variables
such as turnaround times and the incidence
of problems such as specimen errors.
iv. Identify and implement solutions for problems
that occur.
The following pages will highlight the most important errors

which can occur in the pre-analytical phase. For a more
detailed discussion of pre-analytical quality assurance users
should consult textbooks on the subject (1, 2), documents
from professional bodies such as NCCLS (3-4) or IFCC (5) and
the various references cited in the following pages..
12
Steps in Pre-Analytical Quality Assurance

Performance of Analysis Request for Analysis
Pre-Analysis Collection Device
Seven steps
Sample Transport to Anticoagulants
Pre-Analytical
Quality
Sample Collection Patient Preparation
Sample Site
13
Collection Device or Container

The ideal collection device for blood gas analysis would be
gas tight, minimise bubble formation during sampling, have
a high ratio of volume to surface area and have a plunger
that requires a minimum of injection pressure.
All-glass syringes are impermeable to gases so iced sam-

ples will show minimal changes after 1 - 2 hours as shown
in Figure 1 opposite. In addition they require less heparin
and have a low resistance plunger. The disadvantage is that
they are expensive and inconvenient.
Plastic syringes are inexpensive and disposable. Their dis-

advantage is that they are permeable to gases allowing gas
tensions in the sample to move towards atmospheric pres-
sure in the time between sampling and analysis. This is a
significant problem for samples with P O2 values > 150
mmHg (Figure 1).
Capillaries are available from Roche in glass or plastic and

are useful for neonatal samples from the heal or from the
ear in the case of adults. However to obtain a clean sample,
free of bubbles, requires considerable skill.
The Roche Microsampler is a disposable glass capillary

device in a plastic container which has the advantages of
glass and plastic devices. From the data shown in Figure 1
it can also be seen that the P O2 in an iced microsampler is
stable for up to one hour. Data in Figure 1 is from d’Ortho et
al (6).
14
Collection Device/Container
Glass Plastic Glass or Micro-

Syringe Syringe Plastic sampler
Capillary
Advantage: Advantage: Advantage: Advantage:

No leakage Convenience Ideal for Convenience
of gases Cost neonates No leakage
Low resistance of gases
plunger
Disadvantages: Disadvantages: Disadvantages: Disadvantages:
Inconvenience Leakage of More deman- None
Cost gases ding technique
(P O2 > 150)
400
390
▲ ▲
▲
▲
380
P O2 (mmHg)
370 Glass Syringes

Plastic Syringes
360
▲ Microsampler
350
340
0 10 20 30 40 50 60 70
Time (mins)
Figure 1. Change in PO2 levels with time in Microsamplers,
glass & plastic syringes kept at 4° C. Data from d`Ortho et al (6).
15
Anticoagulant - which one?
Almost all critical care tests require the sample to be anti-

coagulated.
The exception is Coagulation tests which are measured on

whole blood without any anticoagulant or additive. In some
cases, coagulation tests may be measured on citrated
(sodium citrate) blood but this will interfere with electrolyte
measurements such as sodium and calcium.
The best universal anticoagulant is heparin, usually the lit-

hium salt. If this is standard, unbalanced lithium heparin
then the only parameters that cannot be measured on such
a sample are Coagulation tests and Lithium. Alternatives to
lithium heparin include the sodium salt but the use of stan-
dard, unbalanced sodium heparin means that such samples
cannot be used for sodium measurement. Note that Roche
make devices containing specially formulated lithium and
sodium heparins which can be used for both lithium and
sodium estimations (see page 20).
A number of other common anticoagulants and preservatives

are used in the laboratory including flouride oxalate and
EDTA, sometimes in combination. Fluoride directly interfe-
res with glucose, lactate and urea sensors and is not suita-
ble for critical care testing samples.
Potassium EDTA binds or chelates ions, particularly calcium

so that an EDTA sample will show a characteristic set of
results with an undetectable or low ionised calcium and a
grossly elevated potassium level.
16
Anticoagulants – Which one?
Standard Other
NO Heparin Anticoagulants
Anticoagulant Anticoagulant eg EDTA,
Oxalate
Only for For all Should not

Coagulation parameters use for
& except any
Lithium Coagulation parameters
&
Lithium
17
Anticoagulant - which Heparin ?
Liquid heparin is usually supplied as the lithium salt at a con-

centration of 1000 IU/l. Only 50µl of this solution is required
to anticoagulate a 1ml blood sample and this volume is
easily mixed with the sample.
The main disadvantage of liquid heparin is that it dilutes all

the parameters – 50µl in 1ml corresponds to a 5% dilution.
Unfortunately more than this volume is often drawn up into
the syringe and the excess is not evacuated after coating
the walls of the syringe. In such cases significant dilution of
parameters can occur as shown in Figure 2 opposite.
The data in Figure 2 indicates that if heparin makes up 10%

or more of the total blood gas sample, there will be signifi-
cant decreases in the measurement of P CO2 and also bicar-
bonate and base excess. The data shown is from Hutchison
et al who also showed that significant errors in diagnosis
and treatment could occur from the results obtained on
samples containing excessive heparin (7).
To overcome this problem for those who wish to continue

using liquid heparin, Roche supply a syringe with a limited
volume of liquid heparin which avoids dilution problems.
18
Anticoagulants – Which Lithium Heparin?
Dry,
Liquid Dry Balanced
Heparin Heparin Heparin
Advantage: Advantage: Advantage:

Easy to dissolve Avoids dilution No dilution effects
problems No chelation of
ions
Disadvantages: Disadvantages: Disadvantages:

Dilution effects Chelation of ions None
Chelation of ions
60
50
% Change in P CO2
40
30
20
10
0
0 10 20 30 40 50 60
% Heparin in Sample
Figure 2. Effects of excess heparin on PCO2 levels.
Data from Hutchison et al (7).
19
Anticoagulant - which Heparin ?
Another solution to overcome the problem with dilution due

to excessive liquid heparin, has been for manufacturers of
collection devices including Roche, to also supply syringes,
capillaries or microsamplers with dry, lyophilised heparin
included in the device. Dry heparin avoids dilution problems,
but needs more mixing to ensure that it is dissolved.
However an additional problem with standard heparin,

whether liquid or dry, is that it binds electrolytes, particularly
calcium. Figure 3 opposite shows the decrease in ionised
calcium levels due to standard dry heparin, which causes a
significant decrease of 0.08 mmol/l in Ca++, even with the
minimum anticoagulant requirement of 50µl of standard
heparin per ml of sample. Larger amounts of heparin cause
a corresponding greater decrease in Ca++. Data from Müller-
Plathe et al (8).
The problem associated with binding of electrolytes by

heparin can be overcome by using a specially formulated
electrolyte-balanced heparin. Figure 4 opposite shows the
ionised calcium results from capillaries containing balanced
heparin compared to reference levels of ionised calcium.
While there is a difference between the two sets of results,
the differences are clinically insignificant. Data from Sachs
et al (9).
All Roche syringes, capillaries and Microsamplers contain

electrolyte-balanced heparin which avoids the problems of
excessive dilution of all parameters and binding of certain
electrolyte parameters.
20
0.00
Decrease in Ion Ca++ (mmol/l)
0.05
0.08
0.10
0.15
0.20
0.25
0.30
50
0 20 40 60 80 100 120 140 160 180 200
Heparin (lU/ml)
Figure 3. Effects of unbalanced dry heparin on ionised Ca++ levels.

Data from Müller-Plathe et al (8).
Roche capillary Ion Ca++ (mmol/l)
3
% deviation - 2.3 %
2.5
2
% deviation 0 %
1.5
% deviation + 0.9 %
1
% deviation + 6.4 %
0.5
0
0 0.5 1 1.5 2 2.5 3
Reference Ion Ca++ (mmol/l)
Figure 4. Ionised Ca++ levels in balanced heparin capillaries

compared to reference levels. Data from Sachs et al (9).
21
Patient Preparation
Before taking the blood sample consideration should be

given to the clinical condition of the patient.
Relatively steady states in blood gases occur quicker in

healthy individuals than in patients with disease. Thus even
spontaneously breathing patients should rest for 5 mins
before the blood sample is collected.
Many critical care testing samples are taken from patients

who are receiving treatment. Depending upon the urgency
to make measurements, appropriate times should be allo-
wed for a steady state to be achieved after a treatment
change and before sampling. For example:
• After intubating a patient, allow 20 min before

sampling.
• When weaning a patient from a ventilator, allow

10 min before sampling.
Taking an arterial blood sample can be a painful and stres-

sful procedure resulting in undue patient anxiety. This
anxiety can cause hyperventilation and affect the blood gas
and pH results. Typical results in such a situation will be a
lower than expected P CO2 and increased pH. Such results,
which are not due to any pathological process, may cause
misdiagnosis and the wrong treatment.
Good blood collection techniques by highly trained and skil-

led staff can avoid this problem and are discussed in more
detail on Page 26.
22
Patient Preparation
Treatment
Rest Equilibrium Anxiety
Spontaneously Allow Avoid pain

breathing appropriate and anxiety
patients time after to prevent
should rest treatment effects on
5 min before changes steady state
sampling before of respiration
sampling
23
Sample Site
Arterial samples are by far the most common sample for cri-
tical care testing because only arterial blood gives a true indi-
cation of oxygenation and acid-base status. Arterial blood
also has the advantage that its composition does not
change from the aorta to the peripheral circulation. Thus a
variety of sites can be used for sampling (see Figure 5) but
the commonest sampling sites are the radial or femoral arte-
ries.
In some cases arterialised capillary blood can be used as a

substitute for arterial blood. This is most often used in the
case of premature babies and neonates when the sample is
usually taken from the heel. Capillary samples can provide
similar values to arterial blood for all parameters except oxy-
genation, where significant differences may exist between
arterial and capillary P O2. This difference can be reduced by
arterialisation or warming the vasculature prior to sampling
(see Page 26).
Peripheral venous samples may be used for certain critical

care parameters such as electrolytes, coagulation tests, glu-
cose and cardiac markers.
Peripheral venous blood is not suitable for special oxygena-

tion parameters such as mixed venous P O2 which are used
to calculate additional parameters such as arterio-venous
oxygen difference. Mixed venous P O2 requires sampling
from a catheter in the pulmonary artery.
Repeated sampling from an artery or vein is best provided

via an in-dwelling catheter.
24
Sample Site
Artery Capillary Vein Catheter/

Cannula
Most common Often used in Used to Cannula

sampling site neonates assess shunts convenient
for multiple
Can be used Requires Peripheral samples
for all critical arterialisation blood not
care para- to give correct suitable for Catheters
meters P O2 results oxygenation used for mixed
parameters venous
samples
Sample Site
Axilary artery
Brachial artery
Ulnar artery
Radial artery
Femoral artery
Figure 5. Preferred sites

of the radial, brachial
Dorsalis pedis artery and femoral arteries for
arterial blood sampling
25
Sample Collection
Collection of blood is a specialised technique which requi-

res considerable training and skill. Only the most important
requirements will be mentioned here and users must con-
sult the documented collection procedures in their own
institution for more details.
The most important requirement is that all samples must be

collected in a way that minimises discomfort and trauma to
the patient. This is particularly important in the case of arte-
rial samples where access to arterial blood can sometimes
be difficult. Other important requirements for arterial sam-
pling are avoiding contamination with air and venous blood.
If capillary sampling is required, the heel or ear must be war-

med prior to collection in order to dilate the arterioles and
achieve a degree of arterialisation. The higher the degree of
arterialisation, the closer should be the agreement between
capillary and arterial P O2 but there is controversy in the lite-
rature about whether arterialised capillary blood is a satis-
factory substitute for arterial blood (2).
Figure 6 illustrates the techniques for collecting blood from

the heel in the case of the neonate or the ear for adults. For
capillary samples avoiding contamination of the sample with
ambient air can be difficult but can be facilitated by keeping
the capillary close to the puncture site. When the capillary is
full and depending upon its size, the use of a metal flea may
be required to ensure mixing of the sample with the heparin.
Sampling from peripheral veins should avoid venous occlu-

sion for longer than 2 mins.
26
Sample Collection
Avoid pain, trauma
and contamination with air
Artery Capillary Vein Catheter/

Cannula
Avoid conta- Requires war- Avoid venous Avoid conta-

mination with ming to achieve occlusion mination with
venous blood arterialisation flush fluid
Expel air, Mix, Label
Sample Collection
(a) (b)
Figure 6. Sites of arterialised capillary sampling

from the ear lobe (a) and the heel (b)
27
Sample Collection
When sampling from an in-dwelling cannula or catheter,

care must be taken to ensure that this is purged of flush
solution before sampling blood. Figure 7 shows the effect
on haematocrit and pH results when insufficient volume is
flushed or discarded before taking a sample for analysis. The
effect in both cases is significantly lower results due to dilu-
tion of the blood with flush solution. The volume that needs
to be discarded should be determined for individual cannu-
las and catheters. Data from Dennis et al (10).
When a conventional syringe is used, once collection is

complete, it is vital to dispose of the needle safely according
to documented procedures.
Air bubbles must be removed from the collection device

prior to transport. Such bubbles will affect both the P O2 and
P CO2 but the effects on P O2 are greater and an example of
these is shown in Figure 8 opposite. Generally the effects
are proportional to the size of the air bubble and increase in
proportion to the length of time that the air bubble is in
place. Data from Biswas et al (11).
The placement of analysers nearer to the patient with con-

sequent reductions in the time between collection and ana-
lysis has reduced this problem but good collection techni-
que should still include removal of all significant air bubbles
immediately after collection.
Finally it is important to mix the sample to ensure that it is

anticoagulated and it must be labelled clearly by hand or
with a barcode containing the patient details.
28
True result
40 7.60
Haematocrit
35 7.40
pH
30 7.20
Haematocrit
25 7.00
pH
20 6.80
15 6.60
10 6.40
5 6.20
0 6.00
0-2 2-4 4-6 6-8 8-10 10-12
Aliquot Volume
Page 1
Figure 7. Effects on pH & Hct of contamination with flush solution
Data from Dennis et al (10 ).
18
16 10 % air bubble
14 20 % air bubble
% Increase in PO2
12
10
8
6
4
2
0
0 1 2 3 4 5
Time (mins)
Figure 8. Effects on P O2 levels of contamination with air.

Data from Biswas et al (11).
29
Sample Treatment and Transport –

Effect on PO2
Many critical care parameters are labile and analysis should

be completed as soon as possible after sample collection.
If there is a significant delay in analysis, the major changes

which can occur in a whole blood sample left at room tem-
perature are as follows:
• The presence of air bubbles and permeability of pla-

stic to gases leads to gas changes (see Figure 1).
• Metabolism of blood cells leads to changes in pH,

gases and metabolites.
• Leakage of electrolytes, particularly potassium, from

cells into plasma, leads to spuriously increased potas-
sium levels.
Figure 9 opposite shows the effects of metabolism on P O2

levels in samples collected in glass Microsamplers, one group
kept at ambient temperature and the other group kept at 4°
C; the original P O2 level was 390 mmHg (50 kPa). The use
of glass collection devices minimises any changes in P O2
level due to the diffusion effects which take place in plastic
devices (see Figure 1).
The changes after 15 mins in both samples are not signifi-

cant but after 30 mins, the fall in the P O2 levels of uncooled
samples are significant and reflect the metabolism of blood
cells. However these changes can be prevented if the
syringe is cooled with ice.
These metabolic effects are insignificant at P O2 levels below

150 mmHg and such samples do not need to be cooled for
up to one hour after collection. Data from d’Ortho et al (6).
30
Sample Treatment & Transport
Analysis Analysis Analysis

<15 min 15 - 60 min Pneumatic
15 - 60 min Tube
Room Temp 4o C Room Temp
Ideal situation for Also satisfactory Unsatisfactory for Rapid transport

all parameters for all parameters many parameters but may cause:
Insignificant Cooling prevents May decrease: Leakage of ions

metabolism and metabolism and pH PO2, Ca, Glu, trough vibration.
leakage of gases leakage of ions. May increase: Worsen effect
& ions in 15 min. PCO2, K, Lac. of air bubbles
105
100
95
% Change in PO2
90 Samples at ambient
temperature
85 Samples cooled with ice
80
75
70
0 10 20 30 40 50 60 70
Time (mins)
Figure 9. Effects of metabolism on P O2 levels. Data from d´Ortho et al (6).
31

Effects on Metabolites
The continuing metabolism of blood cells after the sample

has been collected will also affect the levels of metabolites
such as glucose and lactate.
Figure 10 opposite compares the changes in whole blood

glucose over time in specimens kept at room temperature
and those kept at 4°C. The reductions in glucose levels due
to metabolism are similar at both temperatures and even at
60 mins are probably not clinically significant.
In contrast Figure 11 shows the changes in whole blood lac-

tate, again in samples kept at room temperature and those
kept on ice. Here the changes in the room temperature sam-
ples are significant after 30 mins but the resulting increase
in blood lactate can be minimised by cooling the samples.
Data is courtesy of the Dept. of Clinical Biochemistry,
Addenbrookes Hospital, Cambridge, UK.
It should be noted that using preservatives such as Fluoride

Oxalate or Perchlorate to prevent these metabolic changes
is not possible because such agents are not compatible with
the sensors used in critical care testing analysers.
In summary the effects of sample treatment and transport

upon critical care testing parameters can be minimised by
using the following protocol:
1. Samples analysed within 15 mins can be kept at

room temperature.
2. If analysis cannot be carried out within 15 mins.
store the sample in iced water and analyse preferably
within 30 mins but no longer than 60 mins.
3. Samples with P O2 levels greater than 200 mmHg
(26 kPa) should be collected in glass containers if ana-
lysis cannot be completed within 15 mins.
32
OMNI Whole Blood Glucose (mmol/l)
6.5
6.3
WB Glucose at RT
6.1 WB Glucose at 4°C
5.9
5.7
5.5
10 20 30 40 50
Time (mins)
Figure 10. Effects of metabolism on whole blood glucose levels.
OMNI Whole Blood Lactate (mmol/l)
2.6
2.2
1.8 WB Lactate at RT
WB Lactate at 4°C
1.4
1
0 10 20 30 40 50 60
Time (mins)
Figure 11. Effects of metabolism on whole blood lactate levels.
33

Effects of Pneumatic Tube Systems
Transport of laboratory specimens including critical care

testing samples by pneumatic tube systems (PTS) is now
commonplace. The rapid change in speed of such devices
means that they have the potential to affect labile parame-
ters such as P O2, particularly if any air bubbles are present.
In addition they may cause leakage of ions such as potas-
sium due to excessive vibration.
Figure 12 opposite shows the effects of PTS on specimens

with a P O2 of approximately 60 mmHg (8 kPa) with different
bubble sizes present in the sample compared to Control
specimens which were walked to the laboratory. The
increase in P O2 as a result of transport by PTS was only
partly reduced by the incorporation of a liner or cushion
during transport by the PTS.
Figure 13 shows similar effects but because the specimens

had a higher P O2 (340 mmHg, 44 kaPa) the effect of the
bubbles present in the sample and transport by PTS was to
reduce the P O2. Once again the liner had no significant
effect but the effects were lessened, by reducing the speed
of the PTS by 50%.
The above interferences can largely be eliminated by remo-

ving air bubbles from the sample before transport. However
users of PTS need to determine the possible effects on
blood specimens before introducing them routinely. Data
from Astles et al (12).
34
140
120
Control PTS no liner PTS with liner
100
P O2 (mmHg)
80
60
40
20
0
0 0.2 0.5
Bubble Size (ml)
Figure 12. Effects of pneumatic tube transport (PTS)
on P O2 values <100 mmHg. Data from Astles et al (12).
400
Control PTS no liner PTS with liner
350
300
250
P O2 (mmHg)
200
150
100
50
0
0 0.2 0.5
Bubble Size (ml)
Figure 13. Effects of pneumatic tube transport (PTS)
on P O2 values >300 mmHg. Data from Astles et al (13).
35
Immediate Pre-Analysis
At the time of analysis, sample, patient and ideally, treat-

ment (eg F iO2), details must be entered into the instrument
so that a permanent record of identifiable results can be pro-
duced, both on the instrument and for transmission to the
patient’s record. This is most easily done via a barcoded
label on the syringe.
Any air in the sample must be expelled together with any

blood in the luer of the syringe where small clots can often
develop.
The sample must be mixed, particularly if the sample has

been allowed to stand for any length of time and the blood
cells have started to sediment. Mixing is particularly impor-
tant for Hb, Hct and Na parameters. Mixing should be done
by rolling between the hands for at least 15 - 30 sec before
analysis in order to ensure homogeneity.
For injection instruments, samples should be injected slo-

wly and with minimum pressure. The data in Table 1 oppo-
site shows that Syringe 1 – which required excessive injec-
tion pressure and allowed the entry of small air bubbles, had
significantly higher P O2 values over time compared to
Syringe 2, which required less force on the plunger. Data
from Gosling et al (13).
Finally when the sample results are obtained from the

instrument, the collection device should be disposed of
according to documented health and safety procedures.
36
Immediate Pre-Analysis
Enter Expel Mix Inject

Pat & Sample Air & Clots Sample Slowly
ID
Enter patient Expel air Mix sample Avoid

and sample bubbles to ensure excessive
details into Check for homogeneity injection
instrument/ clots in for Hb, Hct pressure or
LIS syringe luer and Na errors for
PO2 and K
Syringe 1 Syringe 2
After 6 min After 6 min
PCO2 53.1 (6.93) P CO2 53.5 (6.98)

P O2 100.5 (13.12) P O2 97.2 (12.69)
After 15 min After 15 min
PCO2 52.8 (6.90) P CO2 53.6 (7.00)

P O2 108.0 (14.09) P O2 100.8 (13.16)
Table 1. Effects of excessive injection pressure on P O2 levels mmHg (kPa).

Data from Gosling et al (13).
37
Summary of Pre-Analytical Quality

Assurance Procedures
In summary the key steps to avoiding errors in the pre-ana-

lytical phase of critical care testing are as follows:
• Use Roche sampling products which are supplied

with balanced heparin, preferably in lyophilised form,
and therefore avoid the potential anticoagulant pro-
blems of excessive dilution and binding of parame-
ters.
• The Roche Microsampler has the additional advan-

tage of minimising pain by its small needle and the
inner part being manufactured from glass, it is parti-
cularly suitable for samples with high P O2 levels.
• Following collection, the specimen must be labelled,

mixed and analysed within 15 minutes.
38
Summary of Pre-Analytical Quality Assurance
Performance of Analysis Request for Analysis
Mix sample and Use Roche Syringe/

enter patient details Capillary/Microsampler
Seven steps
Analyse sample to Use balanced heparin
within 15 min Pre-Analytical
Quality
Avoid air contamination Sample 5-15 min
label and mix sample after treatment
Collect from Radial

or Femoral Artery
39
40
Chapter III Analytical Quality Assurance
Chapter I I I
Analytical
Quality Assurance
41
Analytical Quality Assurance Chapter III
Aspects of Analytical Quality Assurance
The procedures necessary to achieve analytical quality can

be divided into two groups. The first is Monitoring of Analy-
tical Quality often called Quality Control. The majority of this
chapter will be about the processes of quality control inclu-
ding the analysis of control materials followed by simple sta-
tistics and the application of control charts.
Quality Control can either be Internal (IQC) which is a day to

day process organised by the laboratory or External (EQC).
This is more often referred to as External Quality Assurance
(EQA) or Proficiency Testing (PT). These are less frequent
processes, usually organised by an external agency.
The second group of procedures contributing to analytical

quality are termed Control of Analytical Variables and they
include
• Selection of the best or most suitable method or

measurement device.
• Knowledge of the materials used for calibration and

their relationship to secondary and primary standards.
• Instrument maintenance procedures.
• Supply and storage of consumables.
• Good manufacturing practices.
While these aspects may be less familiar to those who are

using instrumentation on a day to day basis, they are no less
important, particularly to those people who are responsible
for the quality of results produced by the instrument. They
will be explained in more detail on Page 80.
42
Aspects of Analytical Quality Assurance
Monitoring of Control of
Analytical Quality Analytical Variables
• Selection of
Quality Control analytical method
• Internal Quality • Calibration materials
Control (IQC)
• Instrument
• External Quality maintenance
Control (EQC) • Inventory control
OR of consumables
Proficiency Testing • Good manufacturing
practice
43
Quality Control Terminology –

Precision & Accuracy
The aim of all quality control procedures is to reduce the

error associated with any analytical process ie high quality is
related to low error. Various terms are associated with
describing the quality of analyses but the two most com-
monly used are Precision and Accuracy.
One approach to understanding the difference in these two

terms is to use the Target analogy (Diagram opposite). If the
arrows or darts are scattered all over the target we can
describe the shooting as neither precise (none hit the same
place) nor accurate (none hits the centre). If the arrows are
all closely grouped but away from the centre we can say that
the shooting is precise but not accurate. If all the arrows are
together in the centre then the shooting is both PRECISE
and ACCURATE.
In the laboratory we usually consider the quality of an ana-

lytical method in terms of how it compares to a previously
established method or reference method which is usually of
high quality or associated with low error. The results of pati-
ent samples analysed by the established method and by the
new method can be graphically presented as in the Diagram
Comparing Data.
When the points are scattered either side of the diagonal

line the results are not precise and not accurate. When the
points all lie close to a diagonal line but which is not at a 45°
angle then the results are precise but not accurate. If the
points all lie close to a diagonal line and it lies at a 45° angle,
then the results are both precise and accurate.
44
Quality Control Terminology -The Target Analogy
• Scattered • Close hits • Close hits all

hits away but away on target
from target from target
• Not precise • Precise • PRECISE
• Not accurate • Not accurate • ACCURATE
Quality Control Terminology - Comparing Data

New Method
New Method
New Method
Reference Method Reference Method Reference Method
• Scattered • Close points • Close points

points on both but to one around line
side of line side of line of identity
of identity of identity
• Not precise • Precise • PRECISE

• Not accurate • Not accurate • ACCURATE
45
Types of Error
Errors associated with analytical methods can be classified

according to two types. Figure 14 shows a similar graphical
plot to that shown on the previous page where two
methods are compared. If there was complete agreement
between the methods, all the points would lie on the solid
diagonal line or the line of identity.
In reality, complete agreement rarely exists because of

errors in both of the methods. The scatter of points or
results on either side of the line (negative and positive)
represents Random Error and the greater the scatter, the
higher the random error or the poorer the precision or repro-
ducibility of the result.
Random error is often due to factors such as instability in

the instrument, variations in temperature, reagents, techni-
ques or operator. Other words which are used in the litera-
ture to describe this random error include imprecision, and
repeatability.
Systematic error in a new method produces results which

are either high or low compared to the reference method.
From Figure 15 opposite we can see that Systematic Error
can either be Constant in that it is high or low by the same
amount or it can be Proportional which means that it varies
according to the concentration of the analyte being mea-
sured.
Constant Systematic Error can be due to an interfering sub-

stance which reacts with the reagent to give a false signal.
Proportional Error can be caused by incorrect standardisa-
tion or calibration. Systematic error is often described by
terms such as Accuracy or Bias.
46
25
20
New Glucose Method
15
10
0
0 5 10 15 20 25
Glucose Reference Method

Figure 14. Random error between two glucose methods.
25
Constant Error
20
New Glucose Method
Proportional Error
15
No Error
10
0
0 5 10 15 20 25
Glucose Reference Method
Figure 15. Different types of systematic error between two glucose methods.
47
Concept of Total Error
While it is useful to know the various types of error which

can affect analytical results, it is most important to know the
Total Error of any particular method. The Total Error repre-
sents the sum of all the different errors combined and the
final analytical quality is dependent upon the Total Error (14).
How Total Error relates to the individual error components

is illustrated in Figure 16 opposite. The Random Error can be
represented as the distribution of results around a central
mean value. Such a distribution of results would be obtained
if multiple analyses were performed on the same patient
sample. The shape of this distribution is a characteristic bell-
shaped curve called the Normal Distribution. The larger the
Random Error or the lower the precision, the wider will be
the distribution of results.
The Systematic Error in Figure 16 is represented by the shift

of the central value of the distribution from the True Value.
In this example where the errors occur in the same direction
it can be seen that the Total Error is larger than either the
Random or the Systematic Errors alone and therefore Total
Error gives a more realistic estimate of the analytical quality.
48
Observed True
values value
—
X µ
Random Error
— –
X µ
Systematic Error
Total Error
Figure 16. The total error concept of accuracy (14).
49
Principles of Control Charts
Quality Control is based on the principles of Control Charts

which are graphical displays of results for control materials
obtained over time. The values obtained are compared to
the known values for the control materials which are repre-
sented by a range of acceptable values called the control
limits.
Calculation of Control limits is described in more detail on

Page 58. It is assumed that repeated measurements of the
same sample, or the error distribution of the analytical
method, will conform to a Normal or Gaussian Distribution
and therefore we can calculate the Control Limits using the
Mean ± 2 or 3 Standard Deviations (SD). If we use 2 x SD
this will include 95% of all results while 3 x SD will include
97.5% of control results.
How different error distributions translate into control charts

is shown in Figures 17 and 18 opposite (15). Figure 17 (a)
represents the normal distribution of results when the ana-
lytical method is working optimally and this corresponds on
the Control Chart below in Figure 18, with all results being
distributed around the mean value but within the control
limits.
In (b) the distribution shows a shift of values away from the

mean, indicating a systematic error or accuracy problem
with the method, and this is reflected in control values being
on one side of the mean and in some cases outside the con-
trol limit.
In (c) there is a problem with the precision of the method

which produces a wider distribution of results and on the
control chart this is shown as a wider scattering of results
on both sides of the mean value, with some results outside
the limits.
50
a) Stable b) Accuracy c) Precision

performance problem, problem,
shift in mean increase in
standard
Observed Control Concentration
deviation
control limit
control limit
Figure 17. Frequency distribution of different error conditions.
Frequency of Observation
Observed Control Concentration
control limit
control limit
Figure 18. Representation of above error conditions as a control chart.
51
Types of Quality Control
Quality Control procedures can be classified as Internal Qua-

lity Control (IQC) or External Quality Control. The latter is
often called External Quality Assessment (EQA) and in the
United States, EQA is better known as Proficiency Testing
(PT).
IQC is performed continuously by all laboratories and deter-

mines whether patient results are reported. In that sense
IQC is a real-time process. IQC is primarily about the preci-
sion or reproducibility of analytical methods and ensures
that sequential results on the same patient are comparable
and of similar quality. This is of obvious importance in the
critically ill patient who may have multiple analyses perfor-
med over extended periods of time.
Usually IQC is performed through the analysis of stable con-

trol materials but in some situations it can be assessed via
patient data.
EQA or PT primarily compares the analytical quality of diffe-

rent instruments and/or different testing sites. It is not per-
formed by all laboratories and where it does take place, it
usually occurs at intervals varying from once per fortnight to
once per year.
The EQA or PT process involves samples of a stable control

material being distributed by an external agency. Following
analysis by the laboratory the returned results are proces-
sed to allow the retrospective comparison of results from
different laboratories and comparison of all the results to the
so-called "True” value.
52
Types of Quality Control
Internal Quality External Quality

Control Control
• Real time process • Proficiency testing

in USA
• Used on a day to day
basis to determine • Retrospective process
acceptability of results
• Used to compare
• Can use stable control performance of testing
material or patient data with other laboratories
• Organised by the • Uses stable controls
laboratory
• Organised by external
agencies
53
Types of Quality Control Material

and Handling Requirements
Aqueous Controls
These are the most widely used and consist of aqueous
organic and carbonate buffers in equilibrium with predeter-
mined levels of oxygen, carbon dioxide, nitrogen, electro-
lytes and metabolites in solution. Examples are Roche
COMBI-trol or AUTO-trol.
Fluorocarbon based materials.

These more closely resemble blood in terms of oxygen-
carrying capacity but their major disadvantage is that the flu-
orocarbons can poison ion-selective electrodes and so this
type of control material cannot be used in combination ana-
lysers which measure blood gases and electrolytes.
Tonometered blood materials.

These are human or bovine blood, either fresh or in com-
mercial lyophilised controls. It is the ideal material for blood
gases because it most closely resembles a patient sample
but its major disadvantage is that it requires a specialised
tonometer and carefully calibrated gas mixtures together
with a skilled operator.
Handling of QC material
This must be according to the manufacturers’ instructions.
• Samples must be stored at the right temperature
and usually brought to room temperature before analysis
• Samples must be mixed correctly and excessive agi-
tation avoided
• Samples should not be excessively warmed before
analysis
• Samples should be analysed without delay after ope-
ning the ampoule.
54
Types of Stable Quality Control Material
Aqueous Fluorocarbon Tonometered

Controls Emulsions Blood
• Buffers equilibrated • Fluoridised organic • Human or bovine

with gases and compounds blood tonometered
containing other with defined gas
analytes • P O2 carrying mixtures
proprieties more
• Most widely used closely resemble • The best material
material blood for blood gases
• Disadvantage is • Disadvantage is • Disadvantage is
sensitivity to P O2 fluorocarbons the need for special
contamination poison ISEs equipment & skills
Handling conditions for QC materials
Read manufacturer´s instructions
Storage Mixing Temperature Timing
Bring material Avoid excessive Avoid excessive Analyse immed-

to RT before agitation before warming before iately after vial
analysis if analysis analysis is open
stored at 4°C
Develop a written protocol for QC handling
55
Oxygen buffering capacity

of different QC materials
One of the major differences between the various QC mate-

rials described previously is in relation to their oxygen solu-
bility or oxygen-buffering capacity and this is compared in
Figure 19 opposite (16).
The presence of haemoglobin in blood and the shape of the

oxygen-dissociation curve means that blood has high oxy-
gen buffering or resistance to changes in P O2 at low to
moderate levels of P O2. This makes tonometered blood the
ideal QC material for P O2 measurement but for reasons dis-
cussed previously, it is not a practical material on a routine
basis.
In contrast to blood the most widely used aqueous materi-

als have very low oxygen solubility in water and therefore
they have no buffering capacity and are very sensitive to
changes in P O2 which can occur if the sample is contami-
nated with atmospheric air. The implications of this for P O2
measurement will be further discussed on page 76.
Fluorocarbons have an intermediate status in terms of oxy-

gen solubility, better than water but not as good as blood,
especially at low P O2 levels.
56
Blood
Buffer capacity
Fluorocarbon
Water
PO 2
Figure 19. Oxygen buffering ability of different

control materials at varying P O 2 levles.
57
How to establish an Internal

Quality Control Programme
The first step in establishing a QC program is to select a sui-

table control material, usually from a commercial source.
Such materials may come with unassayed values but Roche
quality control materials such as COMBI-trol and AUTO-trol
are supplied with stated means and ranges of values for par-
ticular instruments. These values can immediately be used
to establish a Control Chart for each analyte.
However it is recommended that individual laboratories

check that the stated values and ranges are correct by mea-
suring the material on their instrument(s) over a minimum
period of 20 days, followed by calculation of the Mean, Stan-
dard Deviation (SD) and Ranges. These values may show
slight differences to the stated values but they will more clo-
sely reflect the performance of their instrument(s) and they
should then be used to construct the control chart.
The typical control chart, often called a Levy-Jennings chart

is shown in Figure 20 opposite. The concentration of ana-
lyte, eg Glucose is on the vertical axis and the Run Number
on the horizontal axis. Additional dotted and hyphenated
lines indicate the allowable limits within which the QC
values should fall. The dotted lines correspond to the Mean
Value ± 2 Standard Deviations (SD) while the hyphenated
line corresponds to the Mean ± 3 Standard Deviations (SD).
It is obviously important to ensure that QC samples are sto-

red, handled and analysed according to the manufacturers’
instructions. This is particularly important for blood gases
where incorrect procedures such as excessive shaking and
warming or delays in analysis after the QC ampoule is ope-
ned, can lead to incorrect results. All QC samples should be
aspirated into the instrument with an ampoule adapter.
58
How to establish a QC programme

Select suitable
QC material
Use manufacturer’s Determine own

stated mean & range mean & range
Construct control
chart with mean
and allowable limits
Analyse and
record QCs at
specified times
7
3 x SD
6.5
Glucose (mmol/l)
2 x SD
6
5.5
4.5
4
0 4 8 12 16 20
Run Number
Figure 20. Internal QC or Levy-Jennings Control Chart.
59
How to use a QC Programme

on a daily basis
A protocol for describing how QC is to be performed on a

daily basis must specify how often QC samples are to be
analysed. In some countries such as the United States the
frequency of QC analysis is determined by legislation (17).
The most common practice is to analyse QC samples 3

times per day, with a different level of QC on each occasion.
In addition QC samples should be analysed after any routine
maintenance procedure and after any problems have been
resolved with the instrument.
Following analysis of the QC sample the results are plotted

onto the chart and checked to see that they are within the
chosen limits, either within 2 SDs or 3 SDs of the mean. If
the results are within the chosen limits patient samples can
be analysed.
If the QC result is outside the limits then an Out-of-Control

procedure must be followed as shown in the diagram oppo-
site. This will initially require repeat analysis of a QC sample,
partly to check that the out-of-control result was not due to
incorrect sample handling. If the result obtained is still out-
side the limits then the instrument should be recalibrated,
followed by a repeat QC analysis. If the QC remains out-of-
control then an instrument troubleshooting procedure
should be followed until the fault is found and corrected.
All out-of-control results should be plotted on the chart

together with a comment as to the possible cause and how
it was corrected.
60
How to use a QC Programme on a daily basis

Analyse QCs at
specified
time intervals
After any 3 times After any

maintenance per instrument
procedure 24 hours problems
Record QC
values on
QC Chart
QC OK QC NOT OK
Analyse Follow
patient out-of-control
samples procedure
Responses to Out-of-Control Situations
QC is outside limits
Note QC value QC OK Analyse patient samples

Analyse new QC
QC not OK
Note QC value
Recalibrate QC OK Analyse patient samples
Analyse new QC
QC not OK
Note QC value
Troubleshoot
Instrument
61
Simple QC limits, Westgard Rules

& Roche MultiRules
The most common control rules that are used for internal
QC are the 2 SD and 3 SD rules. The 2 SD rule is often regar-
ded as a "WARNING” limit because there is a statistical
chance that even when the analytical procedure or instru-
ment is working optimally and in control, 1 of 20 results will
fall either below or above this limit. Thus, results outside of
this limit may not necessarily indicate a problem (Figure 21).
The 3 SD rule is regarded as an "ACTION” because the sta-

tistical chance of result being outside this limit is much
smaller (1 in 100) and therefore there is a strong possibility
that this represents a genuine problem which must be inve-
stigated.
However these simple rules have limitations in detecting a

genuine analytical error ie the 2 SD rule may be too sensi-
tive and result in too many repeat QC analyses while the 3
SD rule may be insensitive in that it allows problems to
develop before taking action.
As a result of these limitations more sophisticated QC rules

have been developed by Westgard et al (18) which reduce the
number of falsely rejected runs and increase the sensitivity
of error detection. These rules have been modified for criti-
cal care testing analyses according to Elsa et al (19) and have
been incorporated in the Roche OMNI QC software as
Roche Multirules. Users of the OMNI instrument can use
the simple 2 SD Range rule described earlier, either alone or
in combination with one or more of the Multirules as shown
in Table 2 opposite.
62
7
Action Limit 3 x SD
6.5 Warning Limit 2 x SD
Glucose (mmol/l)
5.5
4.5 Warning Limit 2 x SD

Action Limit 3 x SD
4
0 4 8 12 16 20
Run Number
Rules based on analysis of 3 QC samples of randomly

selected levels per day
Rule Description Message
12σ • QC measurement is outside Mean ± 2 σ • Warning
13σ • QC measurement is outside Mean ± 3 σ • Action
(2of 3)2σ • Two of three QC measurements • Action

are outside Mean ± 2 σ
22σ • 2 QC measurements of the same • Action

level are outside Mean ± 2 σ
61σ • 6 QC measurements of the same • Action

level are outside Mean ± 1 σ
9Mean • 9 QC measurements are all on • Action
the same side of Mean
Table 2. Roche Multirules based on Westgard Quality Control Rules
63
Long-term Quality Control Performance –

Shift in values
As well as demonstrating QC performance on a day-to-day

basis, the additional value of QC charts is to demonstrate
more subtle changes in QC values which may occur over a
longer period of time.
Figure 22 opposite shows the printed format of the Levy-

Jennings control chart from the Roche OMNI instrument
which automatically plots the analysed QC values on the
chart against the 1, 2 and SD limits shown as 1s, 2s and 3s.
This particular chart shows the daily QC values of Combitrol
Level 2 for glucose between July 24 and August 7, 1999,
and the plotted values indicate that the method is in control
according to the 2 SD rule discussed earlier.
Figure 23 shows a later situation for the same instrument

and method. In the latter half of September 1999, there was
a relatively sudden shift in values downward so that alt-
hough the method appeared precise and the majority of
values are within the 2 SD limit, the QC values were consi-
stently lower than those previously obtained.
Such a shift may have been due to a change in electrode,

calibrator or reagent and this will be more readily detected
when such changes are recorded, as they should be, in the
instrument log.
64
Combitrol 2 Glucose Lot 312 24.07.99 - 07.08.99

3s
2s
1s
1s
2s
3s
Figure 22. Format of Levy-Jennings Control Chart on Roche OMNI Instrument.

3s
2s
1s
1s
2s
3s
Figure 23. Levy-Jennings Chart showing shift in QC values.
65
Long-term Quality Control Performance –

Imprecision and Drift
Figure 24 opposite gives a clear demonstration of method

imprecision with wide variations in QC values on a day-to-
day basis. Again, values are almost all within the 3s limit but
several early and consecutive values are outside the 2s limit
which indicates that there may be a problem. By the end of
October it is clear that the method is not working optimally.
Possible causes for this type of performance are many and

they include inappropriate handling of QC material particu-
larly if this type of performance is seen with blood gas mea-
surements.
A different long-term QC performance is shown in Figure 25

where QC values are normally distributed around and close
to the mean value and then start to drift upwards, but gene-
rally remaining within the 2s limit. Such a trend may be the
first sign of an electrode which is coming to the end of its
lifetime or deteriorating reagents. By monitoring QC values
in this way, it is possible to implement a solution to the pro-
blem before it starts to adversely affect patient results.
66

3s
2s
1s
1s
2s
3s
Figure 24. Levy-Jennings Chart showing imprecision of QC values.

3s
2s
1s
1s
2s
3s
Figure 25. Levy-Jennings Chart showing development of drift in QC values.
67
Internal Quality Control

using Patient Samples
Although using stable commercial quality control materials

is the mainstay of internal quality control it is also possible
to use the results obtained from patient samples as a means
of monitoring analytical performance.
The most useful application for critical care testing is dupli-

cate analysis of a patient sample on different instruments,
provided that the second analysis is performed as soon as
possible after the first in order to minimise any potential pre-
analytical changes. This procedure is particularly useful for
blood gases because of the limitations of commercial QC
material to assess analytical performance, as discussed ear-
lier on Page 56. Such a procedure can be formalised with
the plotting of the difference between the two results on a
QC chart with limits for allowable performance based on the
standard deviation of the differences (20).
Another application of patient data to monitor analytical per-

formance is to check the results of parameters which are
derived from a combination of tests. Examples are Anion
Gap, Osmolar Gap or HCO3. Anion Gap is calculated from a
number of electrolyte measurements and an incorrect result
for one of these may produce values for Anion Gap which
can be seen to be erroneous (21).
Patient means or the mean value of a test derived from large

numbers of patient samples can also be used to monitor
quality because for many parameters this value is remarkably
stable; significantly different values from previous means
can indicate that the method is out of control. However
while there is increasing interest in this form of internal
quality control, it is not suitable for many critical care testing
parameters (22).
68
Internal Quality Control using Patient Samples
Duplicate Relationship Patient

Analyses with other Means
tests
• Same sample • Based on detec- • Based on premise

analysed on two ting errors when that mean of
different instru- results used to patient result is
ments calculate other relatively constant
parameters
• Rapid analysis • Not suitable
required to mini- • Examples: for critical care
mise pre-ana- Anion Gap testing
lytical errors Osmolar Gap
pH and H+
• Simple QC check
69
External Quality Assessment

or Proficiency Testing
External quality assessment (EQA) or Proficiency Testing

(PT) was briefly introduced on Page 52. The aim of EQA is
to compare and assess the performance of individual labo-
ratories and it is usually conducted by an external agency
on a retrospective basis. The agency is responsible for
assigning target values for the material to be analysed, dis-
tributing the control material, processing the results and
returning reports to laboratories on their performance.
The design of EQA schemes varies between countries but

desirable features include frequent distributions of samples,
rapid feedback of results, informative reports and valid tar-
get values (23).
Table 3 opposite shows an example of data from a Profi-

ciency Testing survey for P CO2. Individual laboratories are
compared according to the particular instrument they are
using, usually called a Peer Group. Each Peer Group has a
Target Value which is usually the mean of the group and an
acceptable range within which individual laboratory results
must fall. For P CO2 the means of different groups of instru-
ments or peer groups is similar but for other parameters the
means may be significantly different.
Figure 26 shows a graphical presentation of EQA data. Indi-

vidual laboratory results for P CO2 are plotted against the
median P CO2 value of all instruments. In this case the ideal
performance for an individual laboratory would be to have all
their results on the central line of identity or within the lines
on either side of the central line which indicate the limits of
acceptable performance.
EQA or PT is compulsory in those countries which have

adopted laboratory accreditation or a similar process of
external review.
70
Instrument No of Mean SD CV Median Low High

Group Labs
1 178 32.6 1.3 3.9 33 29 36
2 239 32.4 1.4 4.2 32 27 37
3 88 29.8 1.6 5.4 30 26 35
4 58 32.2 1.1 3.4 32 30 35
5 127 31.0 1.6 5.2 31 27 35
6 219 32.2 1.1 3.4 32 29 35
Total instruments 3410 31.6 1.9 6.0 32 25 39
Table 3. Comparison of PCO2 results obtained as part of Proficiency Testing survey

Laboratory PCO2 Value (mmHg)
70
▲
60 ▲
▲
50 ▲
▲
40
▲
▲
30 ▲
20 ▲
10
10 20 30 40 50 60 70
Median PCO2 Values (mmHg)
Figure 26. Graphical comparison of PCO2 results

obtained as part of External Quality Assurance survey
71
Special features of Quality Control

on Roche instruments
AUTO QC and QC Consequences

When instruments are located away from direct laboratory
supervision there is the potential for two serious problems
to occur. The first is for QC samples not to be analysed at
appropriate times or in some cases not at all. The second
problem is that QC samples may be analysed, but the
results are ignored and despite indications of an Out-of-Con-
trol situation, patient samples are analysed and possibly
incorrect results are reported.
The first problem has been overcome by the AUTO QC

module which is attached to the OMNI analyser and con-
tains QC ampoules of different levels. The AUTO QC can be
programmed to sample QC samples at specified time inter-
vals. Samples are aspirated into the OMNI, analysed and the
results displayed in an identical way to manual QC samples.
The status of the AUTO QC is indicated on the OMNI screen
as shown in Figure 27 opposite.
As well as ensuring that QC samples are analysed, the other

major advantage is that the AUTO QC eliminates the varia-
bility in QC values which can result from operator handling.
To ensure that there is an appropriate response to QC results,

the Roche OMNI includes QC Consequences software which
can automatically deactivate parameters when QC results
violate either the 2 SD rule or any of the Roche Multirules
discussed earlier. Activated or deactivated parameters are
clearly shown on the OMNI screen as shown in Figure 27.
It is important to note that while AUTO QC and QC Conse-

quences software does lend a degree of automation to the
QA process it is still essential that the person ultimately res-
ponsible for the patient results produced by the instrument,
regularly reviews all the QC data.
72
Parameter is Grey.
out of QC and auto-
matically deactivated
All other parameters

are in Green, in QC
and automatically
activated
Indicates AUTO QC
is connected
Figure 27. OMNI screen showing status of AUTO QC

device and activated or deactivated parameters.
73
Remote Quality Management via OMNILink & AUTO QC

The location of diagnostic devices outside of the central
laboratory and closer to the patient has been termed the
Boundaryless Laboratory (24). While this development has
enabled laboratories to provide a much more responsive
service, many remotely located devices still require regular
visits from laboratory staff for quality assurance purposes
and these are time consuming especially when instruments
are long distances from the laboratory.
To overcome these problems, Roche OMNILink software in

conjunction with the AUTO QC module can provide remote
quality management of multiple analysers located any-
where from meters to kilometers from the central labora-
tory (Figure 28). Instruments are linked via modem or via the
hospital network to the OMNLink server in the central labo-
ratory.
Via a PC running the OMNILink software, central laboratory

staff can readily see the status of all connected analysers
including any malfunctions of electrodes, reagent fill levels
and any other errors. The OMNILink Database screen pro-
vides a history of all calibration, QC and patient data while
via the Remote Control screen the operator can take control
of the analyser and initiate various troubleshooting func-
tions.
These capabilities are further extended when remote instru-

ments include the AUTO QC module since analysis of QC
samples can be remotely initiated. This unique combination
of software and hardware has been extensively evaluated (25)
and the benefits of OMNILink are documented opposite.
74
Figure 28. Management of remote critical care instruments from

Central Laboratory using OMNILink software.
Benefits of OMNILink & AUTO QC
Analytical Labour Service

Quality Savings Quality
• QC samples are • Daily visits to • Problems fixed

always analysed analyser no before users are
longer required aware of problem
• QC analysis
without operator • 90% of problems • Out-of-hours
variability can be fixed problems more
remotely easily fixed
• QC results always
interpreted accor- • Visits to analysers • Selective deactiva-
ding to set rules & can be planned tion of parameters
warning indicated leaves remaining
ones available
75
Quality control of P O2 measurements

The poor oxygen buffering capabilities of aqueous based
controls means that aqueous PO2 measurements are subject
to considerable error (26). This error arises because during the
transport of an aqueous sample from the ampoule to the
measuring chamber, the sample becomes contaminated with
room air, which usually has a much higher P O2 value and
thus the sample value will move towards that of room air.
This error becomes greater as the sample volume decrea-

ses and since the Roche OMNI instrument has one of the
smallest sample volumes, it suffers most from the problem
of air contamination of aqueous control samples.
To compensate for this problem on the OMNI instrument, a

special aqueous mode is available which corrects for conta-
mination and gives the most accurate estimate of P O2 in
aqueous samples. This is shown in Figure 29 opposite
which compares the results obtained for an aqueous sam-
ple in the Blood and Aqueous modes.
Figure 30 opposite compares the performance of Roche

OMNI and OPTI instruments to other unspecified manufac-
turers in an EQA or PT Survey using bovine whole blood and
aqueous samples. OMNI measurements were in the blood
mode for both materials. Thus the OMNI has a major bias
for aqueous material as discussed above but gives accurate
results for the bovine whole blood material.
Despite the biases that are demonstrated when aqueous

materials from EQA or PT surveys are measured in the
OMNI Blood mode, we continue to recommend that custo-
mers use the Blood rather than the Aqueous mode. This is
primarily because the intention of EQA or PT is that QC sam-
ples should be treated in the same way as patient samples.
In addition, in the Blood mode, electrolytes are reported as
Flame Equivalent values, similar to the reference standard.
76
200
Aqueous Mode
Measured PO 2 (mmHg)
160 Blood Mode
120
80
40
0
0 40 80 140 160 200
Target PO 2 (mmHg)
Figure 29. Comparison of OMNI Blood and Aqueous modes
for measurement of P O2 in aqueous control solution
30
25
Aqueous Bias
20
Tonometrol Bias
15
Bias (%)
10
0
-5
-10
-15
Instrument
OMNI OPTI A B C D E F G H
Figure 30. Comparison of OMNI and OPTI measurements with other unspecified
instruments of P O2 bias in Aqueous and Bovine Whole Blood QC Materials.
77
Single-use device & Electronic Quality Control

The conventional QC procedures that we have discussed so
far, such as analysis of 3 QC samples per day, of random
levels, were developed for devices performing multiple ana-
lyses. Now, many so-called unit or single-use devices such
as Roche glucose meters, the OPTI and Cardiac Reader ana-
lysers are all being used in and outside the conventional
laboratory. Using conventional QC procedures on such devi-
ces only tests that particular strip, cassette or cartridge but
obviously it is not possible to do this on every occasion.
The whole area of QC for single-use devices is an evolving

one with a NCCLS Guideline on this topic currently being
developed (27). In the meantime however manufacturers
have developed a number of strategies to ensure adequate
quality control of single-use devices.
One such strategy is for internal procedural controls to be

built into the analytical process. Figure 31 opposite shows
the control lines which appear for negative and positive mea-
surements on the Roche TROPT device for measurement of
Troponin T. Such control lines will only appear if the sample
is properly applied and the reagents have worked correctly.
The OPTI CCA analyser uses a number of electronic checks

– so called Electronic QC – to check various functions of the
instrument. These include a Sample Reference Cassette
(SRC) as shown in Figure 32 compared to a normal patient
sample cassette. Three levels of SRC are available and they
are designed with a stable flourescent material which when
inserted into the instrument, checks for noise and drift in the
optics, electronics and temperature of the instrument. In
addition to the SRCs, the software of the OPTI instrument
includes many other fail-safe electronic checks, which are
performed with every sample measurement.
A formal evaluation of the electronic QC strategy of the

OPTI analyser found that it conformed with the require-
ments of the US CLIA’88 regulations (28).
78
In-built negative and positive

controls for TROPT
After the sample is applied to the test strip, a single line (left)
indicates a negative test result, while two lines (right)
indicate a positive test result.
Figure 31. In-built negative and positive controls for Roche TROPT device
SRC cassette
Figure 32. SRC or Standard reference cassette at front

compared to a normal patient cassette behind.
79
Control of Analytical Variables
Achieving analytical quality is dependent upon controlling a

number of other analytical variables other than those which
are monitored through quality control procedures.
They start with selection of the best or most suitable method

or measurement device. Evaluation is a critical part of this pro-
cess but it is important that the assessment of any device is
performed under conditions which reflect the routine situation
and involve those people who will be using the instrument.
The quality of any analytical procedure is highly dependent

upon the materials used to calibrate or standardise the
method or device. Wherever possible all Roche critical care
testing parameters are calibrated on solutions which are tra-
ceable to standards from the National Institute of Standards
in the United States (NIST).
While some critical care testing devices are simple and vir-
tually disposable, others are relatively large and complex.
Accordingly they require maintenance which must be per-
formed on a regular and documented basis.
Maintaining quality over long periods is dependent upon a

continuous supply of reagents and other consumables, with
minimal changes in batch numbers and stored under the
recommended conditions.
Finally analytical quality is dependent upon the manufactu-

rer supplying devices and consumables which have met all
the requirements of Good Manufacturing Practices such as
traceability of components and constituents, quality control
of components and manufacturing processes, documenta-
tion, conformity to safety requirements, proper labeling and
packing, and adequate product information.
More details about control of analytical variables can be

found in a laboratory textbook such as Tietz (1).
80
Control of Analytical Variables
Method Good
Selection/ Instrument Manufacturing
Evaluation Maintenance Practice
• Evaluate method • Carry out on a • Maintaining

under routine regular & docu- quality of device
conditions mented basis & consumables
Calibrator Inventory
Materials Control of
Consumables
• Major • Maintain supply

determinant of and storage
method reliability conditions
81
82
Chapter IV Post-Analytical Quality Assurance
Chapter IV
Post-Analytical
Quality Assurance
83
Post-Analytical Quality Assurance Chapter IV
Stages in Post-Analytical Quality Assurance
The post-analytical phase of critical care testing starts with

the data or patient results produced by the analytical device
and is completed when the analytical results, together with
other relevant and useful information, is reported to the per-
son responsible for looking after the patient and into the
patient’s medical record. Producing useful clinical informa-
tion in a timely fashion is essentially the science of infor-
matics and it is being assisted by the advances in commu-
nications and information technologies.
The post-analytical phase can be broken down into four com-

ponents. The first stage can be considered as one of inte-
grating the analytical results with other information about the
patient such as demographics, clinical history and treatment.
The second stage is comparing the analytical results with

appropriate reference values. For some parameters there is
also a need to indicate or "flag” when the patient values
reach critical levels, sometimes called "panic” values.
As part of the process of adding additional value to the data,

comments can be added to the patient results which can
assist the clinician or nurse with the interpretation of the
results.
The final stage of the post-analytical phase is reporting of

the data and accompanying information. First this has to be
in an appropriate time frame or turnaround time, which for
some critical parameters, may be in a matter of minutes.
Second the data and information has to be reported into the
patient’s record or at least to a location where a permanent
record will exist.
The post-analytical phase of critical care testing is becoming

more important as laboratories and manufacturers now rea-
lise that their responsibilities lie beyond providing accurate
and precise analytical data.
84
Stages in Post-Analytical Quality Assurance
Patient Record Analytical Data
Reporting/Trans- Integration of data

mission of information with patient/treatment
to medical record information
Steps to
Post-Analytical
Quality
Interpretation Comparison of data
of data with critical values
85
Combining patient information with data
It is obviously essential that any analytical data or patient

result produced by critical care instruments can be used in
a clinically meaningful way so that it contributes to patient
care. This is rarely possible and indeed potentially dange-
rous if only the numerical result is reported.
The upper diagram opposite contains a suggested list of

information which should accompany a patient result. It is
based largely on the information that is supplied with data
produced in the central laboratory and a similar dataset
should ideally accompany critical care testing data produced
at the point of care (29).
Perhaps the most important piece of information that

should accompany the result is the Patient ID or Identifica-
tion. This should really be part of the Pre-Analytical Phase of
testing (see pages 28 and 36) but it is mentioned here again
if only to stress its importance to the testing process.
Clearly such identification is obligatory in the case of patient
data which is sent electronically to another information
system for reporting of the results and for billing purposes.
However patient identification is also advisable even when
data is only stored in the database of the analytical instrument.
In relation to the other ideal requirements shown in the

upper diagram, several Roche Critical Care Testing Analy-
sers have the facility to allow the user to input various addi-
tional parameters in relation to patient demographics, sam-
ple type, treatment and operator identification and these are
shown in the lower diagram.
The OMNI instrument has the largest and most compre-

hensive range of input parameters some of which can also
be entered via a barcode wand. For the Compact and OPTI
instruments, the parameters must be entered via the key-
board.
86
Ideal Minimum Dataset
Patient Sample Test
• Patient ID • Sample ID • Analytical test

• Patient • Date & time • Numerical
demographics of collection or qualitative
• Clinical • Type of result
diagnosis specimen • Reference
• Clinical reason • Date & time range
for testing of analysis • Derived
values
Input Parameters
Compact OMNI OPTI
Patient ID Patient ID Patient ID

Patient Sex Patient Name Patient Sex & Age
Patient Temp Patient Sex & Age Patient Temp
Total Hb Patient Temp Sample Type
Hb Type Sample Number Total Hb
P50 Sample Time/Date Hb Type
Resp. Quotient Sample Type P50
FiO2 Reporting Time/Date Resp. Quotient
Dept. & Location FiO2
Total Hb & Hb Type Ventilator Settings
P50
Resp. Quotient
FiO2
Ventilator Settings
87
Reference and Critical or Panic Values
The need to accompany a patient result with the appropriate

reference range is obvious and should not need empha-
sising. The difficulties of deriving reference ranges for many
critical care parameters means that most laboratories use
ranges derived from the literature.
The original definition of a critical value is a result that sug-

gests that the patient is in imminent danger unless appro-
priate therapy is initiated promptly (30). With most instru-
ments being used directly in critical care units, critical
results can immediately be brought to the attention of
whoever is looking after the patient.
In those situations where the instrument is in the laboratory,

the person responsible for the analysis should alert the
doctor or nurse by telephone or possibly by e-mail. Direct
electronic communication makes the task of reporting
urgent results much easier.
Reference to the literature shows that the list of critical

values goes beyond those available on the OMNI instru-
ment, the most critical of which are shown in the diagram
opposite. Although the reference source for the above
values has been identified, the primary source for these
values is not always clear. Laboratories are recommended
to discuss these values with the physicians in their institu-
tion before routine application.
As well as highlighting critical values on the report produced

by the instrument, laboratories should also consider similar
"flagging” on the information system to which the instru-
ment may be connected.
88
Analyte SI Units Conventional Units
pH or H+ <24 or >62 nmol/l <7.20 or >7.60

PCO2 <2.7 or >9.3 kPa <20 or >70 mmHg
PO2 <5.3 kPa <40 mmHg
+
Na <120 or >160 mmol/l <120 or >160 mmol/l
+
K <2.8 or >6.2 mmol/l <2.8 or >6.2 mmol/l
++
Ca <0.82 or >1.55 mmol/l <3.28 or >6.20 mg/dl
Glu <2.2 or >25 mmol/l <40 or >450 mg/dl

tHb <70 or >200 mmol/l <7.0 or >20 mg/dl
Table 4. Critical or “Panic” values for certain critical care parameters.
89
Interpretation of data
Interpretation of data falls into two categories. The first

involves deciding whether a clinically significant change has
taken place in a parameter since it was last measured. Such
situations are common in the critically ill where parameters
are repeatedly measured in order to monitor treatment.
Whether a significant change has occurred depends upon

the analytical precision of the measurement. For example
the precision (SD) of ionised calcium measurements is 0.05
mmol/l at 1.2 mmol/l. So a result must lie outside of the
range 1.10 to 1.20 (1.2 ± 2.0 SD or ± 0.10) for there to be a
95% chance that it is significantly different.
The second interpretative situation is the process of making

a clinical diagnosis from one or several values. Correct inter-
pretation is often dependent on knowing the clinical history
of the patient and in particular any treatment that they might
be receiving.
Interpretation of acid-base results can be difficult but the

algorithms shown in the Figures 33 and 34 opposite are rela-
tively simple since they use only 3 parameters, pH, P CO2
and HCO3- (31). Other charts and algorithms for acid-base
balance exist in the literature (32).
Expert systems are also available for more automated inter-

pretation of data but have not yet gained widespread accep-
tance. This may change with advances in computing tech-
nology and the realisation that physicians need assistance
to deal with the growing amount of data and information
that they have to process on a daily basis.
90
pH < 7.35 (acidaemia)

low Metabolic acidosis
PCO2
normal/high Incompatible
low HCO3-
normal/high Incompatible
normal HCO3 -
1. Metabolic acidosis
low 2. Mixed metabolic &
high HCO3- respiratory acidosis
normal Acute respiratory acidosis
high Chronic respiratory acidosis
low
Mixed metabolic &
respiratory acidosis
Figure 33. Diagnostic algorithm for interpretation of a low pH value.
pH > 7.45 (alkalaemia)

high Metabolic alkalosis
PCO2
normal/low Incompatible
low HCO3-
normal/low Incompatible
normal HCO3 -
1. Metabolic alkalosis
high 2. Mixed metabolic &
high HCO3- respiratory alkalosis.
normal Acute respiratory alkalosis
low Chronic respiratory alkalosis

high
Mixed metabolic & respiratory alkalosis

cardiopulmonary arrest
respiratory failure with anoxia
Figure 34. Diagnostic algorithm for interpretation of a high pH value.
91
Turnaround Times
An important aspect of post-analytical quality assurance is

to provide patient results and related information within an
appropriate time interval after collection of the specimen,
the so-called Turnaround Time. There are various definitions
of Turnaround Time (see Figure 35 opposite) but one defini-
tion is the time between collection of the sample and the
delivery of the information to the clinician (33); this is someti-
mes referred to as the "vein to brain” time.
For many routine laboratory tests this time interval can be

up to several hours. However for critically ill patients, the
results for some parameters are needed within minutes of
the sample being collected. The need for Turnaround Times
in minutes is one of the driving forces behind Point-of-Care
Testing (POCT). Placement of devices directly in Critical
Care Units and other clinical areas greatly reduces the time
taken to transport specimens to laboratories and avoids the
delays than can happen within the laboratory itself.
An alternative to the placement of instruments in clinical

areas is the use of Pneumatic Transport Systems to rapidly
transport specimens from critical areas to the laboratory.
Users of such systems should be aware of the possible
effects on the specimen (see page 34).
No matter where the actual testing is located it remains

important for laboratories to monitor periodically the tur-
naround time for key parameters. If such times do not meet
the needs of users then steps have to be taken to improve
the situation through an appropriate quality planning and
implementation strategy.
92
Laboratory Turnaround Time
Laboratory Clinician
Test Specimen receives Patient
Request Collected Testing Inform- Treated
ation
Clinician
Test Specimen receives Patient
Request Collected POCT Inform- Treated
ation
POCT reduces
Turnaround Time
Figure 35. Turnaround times associated with laboratory testing
and potential reductions achieved with Point of Care Testing.
93
Reporting of data and information
It is clear that rapid analysis of a patient sample is pointless

if the result does not reach the person who needs that infor-
mation to manage and treat the patient. Furthermore the
analytical result together with other relevant information
should be carried forward into the patient record.
However at the present time it is likely that many patient

results from both small and large measurement devices are
not recorded permanently or in hard-copy form. Of those
results that are recorded, this is only achieved by manual
transcription of results which is subject to error. Thus the
general situation of reporting critical care testing data is
represented by the upper part of Figure 36 opposite.
The importance of reporting patient data and information,

both promptly and in a permanent form, is now being appre-
ciated by laboratory professionals and manufacturers. The
task of reporting data promptly and accurately can be greatly
facilitated by linking devices to various types of information
systems. Up to now this has not been an easy task due to
the wide variety of communication interfaces.
In 2000 the Connectivity Industry Consortium, CIC, was for-

med to develop a so-called Connectivity Standard or a com-
mon interfacing standard (34). This will be finalised in 2001
and already, Roche data management systems are CIC
compatible.
With easy connectivity, it is possible to achieve the situation

shown in the lower half of Figure 36, whereby data can be
reliably transmitted and reported to a variety of different
locations so that those responsible for the care of the pati-
ent can access the data. In addition connectivity will facili-
tate the development of the Electronic Medical Record
(EMR) which will contain, in permanent and accessible
form, all patient data.
94
Manual and often unreliable reporting

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95
96
Chapter V Management of testing outside the laboratory
Chapter V
Management
of testing outside
the laboratory
97
Management of testing outside the laboratory Chapter V
Management of testing
outside the laboratory
Two major factors are responsible for the trend towards

Point-of-Care, Near Patient or Decentralised Testing. The
first is changing clinical practice which includes both the
need for more rapid testing and the move towards ambulant
care or medical care outside of the hospital. The second dri-
ving force has been technological advances which have ena-
bled the development of whole blood measurement devices.
Yet, as many laboratory professionals have made clear in the

literature, other factors apart from these driving forces, are
required for testing outside of the laboratory to be a success
and deliver the intended improvements in patient care (35).
To help address the challenges associated with this type of
diagnostic testing various professional bodies from different
countries have produced guidelines which document requi-
rements and provide useful advice for all those embarking
on, or extending their diagnostic services outside of the
laboratory (36 - 38).
These broad guidelines can be modified to take account of

local knowledge and requirements, gained through consul-
tation with all the parties involved, including clinicians, para-
medical staff and laboratory professionals. The end-result
should be a well-defined policy or local guideline which
determines all the necessary practices to achieve effective
diagnostic testing outside of the laboratory.
At the present time only a few countries have fully accredi-

ted diagnostic laboratories and in most of these, such accre-
ditation does not usually include testing outside of the labo-
ratory. Yet there are powerful arguments to include such
testing within the accreditation system (39) and it is likely that
many laboratories will move to voluntary and then manda-
tory accreditation of their complete diagnostic service, no
matter where it is located.
98
Management of testing outside the laboratory
Professional Local
Guidelines Requirements
Local
Guidelines
Voluntary Accreditation
Mandatory Accreditation
99
Management of testing outside the laboratory Chapter V
Local guidelines for testing

outside the laboratory
The practices which should be addressed in a local guide-

line for testing outside of the laboratory, are essentially no
different from those that take place in the central laboratory.
Wherever testing takes place the overall goal must be to
deliver a quality service.
However the emphasis of a management policy for Point-

of-care or Near Patient Testing has to reflect two important
factors. The first is that testing is often being carried out by
non-laboratory personnel and second, such personnel can-
not be supervised on a 24 hours basis.
Some of the important issues to be addressed in a local gui-

deline for POCT are shown in the diagram opposite. Orga-
nisation and Management may be based around a POCT
Committee which includes all the interested parties and
ensures a cooperative approach.
Documentation of staffing and direction should clearly state

who is the director and who is accountable for the various
aspects of the service.
Devices and equipment must be appropriate to the task, in

a safe and workable environment, and maintained according
to the manufacturer’s instructions.
The involvement of non-laboratory staff means that staff

development and education takes on an extra importance as
was emphasised on Page 8. Local policy must include regu-
lar training with assessment of the operator’s competence.
Apart from the obvious need to document all practices con-

sideration has to be given to making instructions as simple
and concise so that users readily adopt the necessary skills
and techniques.
100
Local guidelines for testing outside the laboratory
Staff
Organisation & Facilities & Development
Management Equipment & Education
• Strategy, scope • Appropriate equip- • Documented

& management ment in sufficient training program
of provider unit space & a safe for all staff
environment
Staffing & Policies &

Direction Procedures
• Designated director • Written procedures

with lines of for sample handling
accountability for device operation &
all staff result handling
101
Quality Assurance & Critical Care Testing References
References
1. Tietz Textbook of Clinical Chemistry. Eds Burtis C &

Ashwood ER. Saunders 3rd ed. Philadelphia, USA 1999.
2. Principles and Practice of Intensive Care Monitoring. Ed

Tobin MJ. pp 107 - 122. McGraw Hill, USA1998.
3. NCCLS. Blood gas pre-analytical considerations: Specimen

collection, calibration and controls. Document C27 - A.
ISBN 1-56238-190-3. Wayne, PA, USA: NCCLS 1993.
4. NCCLS. Percutaneous collection of arterial blood for labo-

ratory analysis. Document H11-A2. ISBN 1-56238-130-X.
Wayne, PA, USA: NCCLS 1992.
5. Burnett RW, Covington AK, Fogh-Anderson N et al. Recom-

mendations on whole blood sampling, transport and stor-
age for simultaneous determination of pH, blood gases and
electrolytes. JIFCC 1994; 6: 115 - 120.
6. d’Ortho MP, Delclaux C, Zerah F, Herigault R, Adnot S, Harf A.

Use of glass capillaries avoids time changes in high blood
oxygen tension observed with plastic syringes. Submitted
for publication 2000.
7. Hutchison AS, Ralston SH, Dryburgh FJ et al. Too much

heparin: possible source of error in blood gas analysis. BMJ
1983; 287: 1131 - 2.
8. Müller-Plathe O, Schreiber R. Electrolyte adapted heparin

solution for the determination of gases, electrolytes and
substrates in whole blood. Metholodologies and clinical
applications of ion-selective electodes. 1989; 10: 89 - 94.
9. Sachs C, Rabouine P, Kindermans C et al. Evaluation of

capillaries for ionized calcium measurements. Ann Clin
Biochem. 1992; 28: 96 - 301.
102
References Quality Assurance & Critical Care Testing
10. Dennis RC, Ng R, Yeston NS et al. Effect of sample dilutions

on arterial blood gas determinations. Crit Care Med 1985;
13: 1067 - 8.
11. Biswas CK, Ramos JM, Agroyannis B et al. Blood gas

analysis: effects of air bubbles in syringe and delay in
estimation. BMJ 1982; 284: 923 - 7.
12. Astles RJ, Lubarsky D, Loun B et al. Pneumatic transport

exacerbates interference of room air contamination in
blood gas samples. Arch Pathol Lab Med 1996; 120: 642 - 7.
13. Gosling P, Dickson G. Syringe injection pressure: a neglec-

ted factor in blood P O2 determination. Ann Clin Biochem.
1990; 27:147 - 51.
14. Westgard JO, de Vos DJ, Hunt MR et al. Method evalua-

tion. Houston, USA, American Society of Medical Techno-
logy, 1978.
15. Westgard JO & Klee GG. Quality Management: Tietz Text-

book of Clinical Chemistry. Eds Burtis C & Ashwood ER. pp
384 - 418. Saunders 3rd ed. Philadelphia, USA 1999.
16. Burnett RW. Current issues in quality control and proficiency

testing for blood gases and electrolytes. Quality control in
the clinical laboratory ’95. Eds Ohba Y, Kanno T, Okabe H et
al. pp 247 - 258. Excerpta Medica, Tokyo 1995.
17. Public law 100 - 578. Clinical Laboratory Improvement

Amendments of 1988. Stat 42 USC 201. H.R. 5471 1988;
October 31.
18. Westgard JO, Barry PL, Hunt MR et al. A multi-rule Shewhart

chart for quality control in clinical chemistry. Clin Chem
1981; 27: 493 - 501.
19. Elsa F, Quam BS, Lorene K et al. A comprehensive statistical

quality control program for blood gas analysers. J Med Tech
1985; 2.
103
Quality Assurance & Critical Care Testing References
20. Bokelund H, Winkel P, Statland BE. Use of randomised

duplicates to evaluate sources of analytical error. Clin Chem
1974; 20: 1507 - 12.
21. Cembrowski GS, Westgard JO, Lyama-Kurtycz DF. Use of

anion gap for the quality control of electrolyte analysers.
Am J Clin Path 1983; 79: 688 - 96.
22. Cembrowski GS, Chandler EP, Westgard JO. Assessment

of "Average of normals” quality control procedures and
guidelines for implementation. Am J Clin Path 1984; 81:
492 - 99.
23. Bullock DG. Quality control and quality assurance. pp 157 -

75. Point of Care Testing Eds Price CP & Hicks JM AACC
Press, Washington, USA, 1999.
24. Lazarus L. The clinical scientist as information scientist.

Clin Biochem Reviews 1993; 14: 112 - 7.
25. Hirst D & St John A. Keeping the spotlight on quality from

a distance. Accred Qual Assur 2000; 5: 91 - 3.
26. Hansen JE, Feil MC. Blood gas quality control materials
compared to tonometered blood in examining for interin-
strument bias in P O2. Chest 1988; 94: 49 - 54.
27. NCCLS. Quality management for unit-use testing; Proposed

guideline. Document EP18-P. ISBN 1-56238-391-4. Wayne,
PA, USA: NCCLS 1999.
28. Lassig R, Ehrmeyer S, Tusa JT. The role of electronic controls

in an alternative quality control paradigm under CLIA’88 in
the US pp 502 Proceedings of the XVI International Congress
of Clinical Biochemistry. 1996 Association of Clinical Bio
chemists, Cambridge, UK.
104
References Quality Assurance & Critical Care Testing
29. Jones RG. Informatics in Point-of-Care Testing pp 175 - 195.

Point of Care Testing Eds Price CP & Hicks JM AACC Press,
Washington, USA 1999.
30. Emancipator K. Critical values ASCP Practice Parameter.

Am J Clin Path 1997; 108: 247 - 53.
31. Walmsley RN, Cain HJ. Chemical Pathology: an interpreta-

tive pocket book. 1996 World Scientific, Singapore.
32. Goldberg M, Green SB. Computer-based instruction and

diagnosis of acid-base disorders. JAMA 1073; 223: 269 - 75.
.
33. Kost GJ. Guidelines for point-of-care testing: improving
patient outcomes. Am J Clin Path 1995; 104 (Suppl 1):
S111 - S127.
34. Connectivity Industry Consortium http://www.poccic.org
35. Freedman D. Guidelines on Point-of-Care Testing. pp 197 -

212. Point of Care Testing Eds Price CP & Hicks JM AACC
Press, Washington, USA 1999.
36. NCCLS. Point-of-Care Testing. Document SC17-L. ISBN

1-56238-294-2. Wayne, PA, USA: NCCLS 1998.
37. Freedman D, Burnett D, Kay J et al. Guidelines for imple-

mentation of near-patient testing. Association of Clinical
Biochemists 1993, London UK.
38. Janssen HW, Bookelman H, Dols JLS et al. Point-of-care

testing: the views of the Working Group of the Dutch Asso-
ciation of Clinical Chemistry. Clin Chem Lab Med 1999; 37:
675 - 80.
39. Burnett D. Accreditation and point-of-care testing. Ann Clin

Biochem 2000; 37: 241 - 3.
105
Quality Assurance & Critical Care Testing Figures & tables
List of figures & tables
Figure 1. Change in P O2 levels with time in micro

samplers, glass & plastic syringes kept at 4°c.
Figure 2. Effects of excess heparin on P CO2 levels.
Figure 3. Effects of unbalanced dry heparin on ionised Ca++

levels.
Figure 4. Ionised Ca++ levels in balanced heparin capillaries

compared to reference levels.
Figure 5. Preferred sites of the radial, brachial and femoral

arteries for arterial blood sampling.
Figure 6. Sites of arterialised capillary sampling from the heel

(a) and ear lobe (b).
Figure 7. Effects on pH & Hct of contamination with flush

solution.
Figure 8. Effects on P O2 levels of contamination with air.
Figure 9. Effects of metabolism on P O2 levels.
Figure 10. Effects of metabolism on whole blood glucose

levels.
Figure 11. Effects of metabolism on whole blood lactate levels.
Figure 12. Effects of pneumatic tube transport (PTS) on P O2

values <100 mmHg.
Figure 13. Effects of pneumatic tube transport (PTS) on P O2

values >300 mmHg.
Table 1. Effects of excessive injection pressure on P O2

levels.
106
Figures & tables Quality Assurance & Critical Care Testing
Figure 14. Random error between two analytical methods.
Figure 15. Different types of systematic error between two

analytical methods.
Figure 16. The total error concept of accuracy.
Figure 17. Frequency distribution of different error conditions.
Figure 18. Representation of above error conditions as a control

chart.
Figure 19. Oxygen buffering ability of different QC materials.
Figure 21. Simple QC warning and action rules.
Table 2. Roche Multi Rules based on Westgard Quality

Control Rules.
Figure 22. Format of Levy-Jennings Chart on Roche OMNI

instrument.
Figure 23. Levy-Jennings Chart showing shift in values.
Figure 24. Levy-Jennings Chart showing imprecision.
Figure 25. Levy-Jennings Chart showing development of drift.
Table 3. Proficiency Testing – Numerical comparison of P CO2

results.
Figure 26. External Quality Assurance – Graphical presentation.
Figure 27. Set-up screen for Auto QC module.
Figure 28. Remote Quality Assurance using OMNILink and

Auto QC.
107
Quality Assurance & Critical Care Testing Figures & tables
Figure 29. Measurement of P O2 in aqueous materials using the

Roche OMNI.
Figure 30. Comparison of P O2 measurements in aqueous and

bovine materials.
Figure 31. In-built negative & positive controls of Roche TROPT

strip.
Figure 32. SRC Cassette for electronic QC of Roche OPTI CCA.
Table 4. Critical values.
Figure 33. Algorithm for interpretation of a low pH result.
Figure 34. Algorithm for interpretation of a high pH result.
Figure 35. Turnaround times.
Figure 36. Possible ways to report patient information.
108
Index Quality Assurance & Critical Care Testing
Index
Accreditation 8, 98
Accuracy 44
Air bubbles 28, 36
Analytical variables, control of 80
Anticoagulants -
Heparin 16
EDTA 16
Flouride-Oxalate 16
Arterial sample collection 24
Auto QC 72, 74
Capillary sample collection 26

Catheter or cannula samples 28
Collection devices or containers 14
Control charts 50, 58 - 67
Control materials –
Types 54
Handling requirements 54
Oxygen buffering characteristics 56
Critical or panic values 88
Documentation 8, 100
Electronic or single-use device QC 78

Error –
Types in critical care testing 6
Constant ,systematic and total error 46 - 49
External quality control or assessment 70
Glucose –
Effect of sample transport 32
Heparin -
Liquid 18
Dry 20
Balanced 20
109
Quality Assurance & Critical Care Testing Index
Ionised calcium, effect of heparin 20

Internal quality control –
Using control materials 58 - 67
Using patient samples 68
Interpretation of data 90
Lactate, effect of sample transport 32
Management of testing outside the laboratory 98 - 101

Microsampler 14
Mixed venous sample collection 24
OMNILink & AutoQC 74

Out-of-control procedures 60
Patient -
Identification 27-28, 86
Information, input parameters 86
Preparation 22
Testing cycle 4
P CO2, effect of excess heparin 18
P O2 –
Effect of air bubbles 28
Effect of metabolism 30
Glass vs plastic syringes 14
Buffering capacity of different control
materials 56
Performance in external QC surveys 76
Pneumatic tube systems 34
Point-of-care testing guidelines 98 - 101
Precision 44
Proficiency testing 70
Quality assurance, definition 2

Quality control -
External 52, 70
Internal 52, 58
Monitoring of analytical quality 42
Quality management 8
110
Index Quality Assurance & Critical Care Testing
Reporting of data & information 94
Sample –
Container 14
Collection 26, 28
Injection 36
Mixing 28, 36
Treatment & transport 30 - 35
Sample site –
Arterial 24
Capillary 24
Venous 24
Syringes, glass & plastic 14
Total quality management 2

Training & education 8, 100
Turnaround times 92
Westgard Rules 62
111
Quality Assurance & Critical Care Testing Chapter V

Sandhoferstr. 116
D-68305 Mannheim/Germany
Tel. +49 - 621 - 7590

Fax +49 - 621 759 2902
112
3
3
Quality Assurance
Quality Assurance
This book describes the various quality assurance
procedures at all stages in the patient testing
cycle and how they contribute towards obtaining
the correct patient result.
www.roche.com/poc

Roche Near Patient Testing
D-68298 Mannheim
4.01-3190285
Germany
ISBN 3-88630-250-4

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3

Roche Diagnostics GmbH

This book provides an overview of quality assurance as applied

While laboratory professionals almost live and breathe quality

As with the previous books many people, both colleagues and

My thanks also to Miles Sykes of the Bradford Royal Infirmary,

Dr. Phd. Andrew St John

List of figures & tables 106

Quality and Critical Care Testing

There are many definitions of quality but in relation to dia-

In plain terms this means providing the right result accom-

As part of the evolution of quality systems in healthcare

In order to provide a concise account of the quality proces-

Quality Assurance (QA) can be defined as the management

Quality Control (QC) is just one part of QA and is concerned

Quality in Critical Care Testing

Quality TQM Quality

Quality Assurance and Critical Care Testing

The critical care testing process or patient testing cycle

A simple approach to assessing and improving the quality of

The first pre-analytical stage of the cycle involves collection

The second phase is the actual analysis of the specimen.

The third and final phase is called the post-analytical phase

Quality Assurance & Critical Care Testing

Reporting of Patient Specimen

Adding Value Specimen

Potential Errors in Critical Care Testing

The consequences of not delivering a quality critical care

• Making the wrong diagnosis in a patient

• Patients receiving the wrong treatment

• Patients not receiving treatment or receiving it at the

• Conducting the wrong investigations in a patient

Poor quality is often due to errors occurring in the critical

Ideally each laboratory should conduct a systems analysis of

More details of the potential errors in each phase of the cri-

Major Potential Errors in Critical Care Testing

• Result not reported

Key Aspects of Quality Management

There are a number of important aspects of quality mana-

Training and Education

Audit and Accreditation

Even in those countries where accreditation is not yet esta-

Key Aspects of Quality Management

Docu- Training/ Audit/

All processes All staff carrying All processes

Steps in Pre-Analytical Quality Assurance

The pre-analytical phase of critical care testing starts with

The diagram opposite shows that several distinct stages

While the development of testing nearer the patient has

The aim of pre-analytical quality assurance is to remove or

i. Documentation of step by step procedures.

The following pages will highlight the most important errors

Steps in Pre-Analytical Quality Assurance

Pre-Analysis Collection Device

Collection Device or Container

All-glass syringes are impermeable to gases so iced sam-

Plastic syringes are inexpensive and disposable. Their dis-

Capillaries are available from Roche in glass or plastic and

The Roche Microsampler is a disposable glass capillary

Glass Plastic Glass or Micro-

Advantage: Advantage: Advantage: Advantage:

370 Glass Syringes

Anticoagulant - which one?