Critical Care Testing - Quality Assurance

3

Roche Diagnostics GmbHRoche Near Patient TestingD-68298 MannheimGermany

ISBN 3-88630-250-4

www.roche.com/poc

4.01

-319

0285

3

Qua

lity

Ass

uran

ce

Critical Care TestingQuality AssuranceThis book describes the various quality assuranceprocedures at all stages in the patient testingcycle and how they contribute towards obtainingthe correct patient result.

Critical Care TestingQuality Assurance

Andrew St John

Roche Diagnostics

1

Impressum© by Roche Diagnostics, Mannheim, GermanyCover: !Now Werbeagentur AG, CH-4051 BaselArtwork & Layout: Eva Baumgartner, CH-8200 SchaffhausenPrinted by: stamm+co, CH-8226 SchleitheimFirst Edition April 2001

Preface

This book provides an overview of quality assurance as appliedto the critical care testing process and it is intended for a broadaudience. First and foremost that audience includes those peo-ple who have received no formal training in laboratory practicessuch as clinicians, nurses and paramedical staff but who arenow using diagnostic devices.

While laboratory professionals almost live and breathe qualityassurance, the topics of pre-analytical and post analytical qua-lity assurance have not perhaps received the attention theydeserve in the past but are especially important to the criticalcare testing process. Therefore I would hope that my scientificcolleagues will also find new and relevant information in thisbooklet. Last but by no means least I would encourage my com-pany colleagues to use this book to help them provide some ofthe answers to the growing number of questions that custo-mers now direct to the suppliers of diagnostic devices, many ofwhich are related to issues of quality.

As with the previous books many people, both colleagues andcustomers, 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 Universityof Wisconsin, USA whose previous publications in the area ofquality 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 RocheDiagnostics, Graz. Finally of course, I must acknowledge EvaBaumgartner who as with the previous books has converted mywriting into the professional publication that you have in frontof you today.

Dr. Phd. Andrew St JohnRoche Diagnostics, Mannheim, Germany

Preface Quality Assurance & Critical Care Testing

3

Contents:

Chapter I

Introduction 1

Quality assurance & the critical care testing cycle

Chapter II

Pre-Analytical Quality Assurance 11

Steps in pre-analytical quality assuranceCollection device or container AnticoagulantsPatient preparationSample site Sample collectionSample treatment and transport Immediate pre-analysisSummary of pre-analytical quality assurance procedures

Chapter III

Analytical Quality Assurance 41

Aspects of analytical quality assurance Terminology, types & principles of quality controlInternal quality control using control materialsInternal quality control using patient dataSpecial aspects of internal quality control on Roche instrumentsExternal quality control using control materialsFactors affecting analytical quality

Quality Assurance & Critical Care Testing Contents

Chapter IV

Post-Analytical Quality Assurance 83

Stages in post-analytical quality assuranceCombining results with patient information Critical or panic valuesInterpretation of dataReporting 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

Contents Quality Assurance & Critical Care Testing

5

Quality Assurance & Critical Care Testing Chapter I

6

Chapter I

Introduction

Chapter I Quality Assurance & Critical Care Testing

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 whichmeets 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 theright time on the right specimen from the right patient.

As part of the evolution of quality systems in healthcaremany laboratories have adopted the principles of Total Qua-lity Management (TQM) which is a structured approach tomeeting quality standards. TQM as shown in the diagramopposite is a feedback cycle which comprises a number ofdistinct processes called Quality Planning, Quality Labora-tory Processes, Quality Control, Quality Assurance andlastly Quality Improvement.

In order to provide a concise account of the quality proces-ses and potential errors in critical care testing this book willconcentrate on the Quality Assurance and Quality Controlaspects. For more details of the principles of TQM, readersshould consult a laboratory textbook such as Tietz (1).

Quality Assurance (QA) can be defined as the managementprocess 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 concernedwith analytical quality ie obtaining the right result.


2


3

Quality in Critical Care Testing

TQMprocesses

inCritical

Care Testing

QualityLaboratoryProcesses

QualityImprovement

QualityPlanning

QualityAssurance

QualityControl

Quality Assurance and Critical Care Testing

The critical care testing process or patient testing cyclecommences by the clinician asking a question about thepatient which is answered by performing a laboratory ana-lysis and providing a diagnostic answer.

A simple approach to assessing and improving the quality ofcritical care testing is to consider the testing cycle in threephases as shown in the diagram opposite.

The first pre-analytical stage of the cycle involves collectionand 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 monitorand control.

The second phase is the actual analysis of the specimen.This analytical phase requires conventional quality controlprocedures such as internal and external quality controlwhich are similar to those for any analytical device.

The third and final phase is called the post-analytical phaseand involves processes such as integration of patient infor-mation with analytical results, comparison to reference andcritical values, interpretation and finally the reporting ofinformation – the diagnostic answer – to the clinician andinto the patient record.


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5

Patient

Pre-Analysis

Analysis

Post-Analysis

Quality Control

Clinical question ?Diagnostic answer !

PatientTestingCycle

Adding Valueto Data

SpecimenTransport

SpecimenCollection

Reporting ofInformation

Quality Assurance & Critical Care Testing

Potential Errors in Critical Care Testing

The consequences of not delivering a quality critical caretesting 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 criticalcare testing process and the diagram opposite shows themajor errors associated with each of the 3 phases whichmake 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 moremanual interventions are required compared to the othertwo phases where a degree of automation exits.

Ideally each laboratory should conduct a systems analysis ofits 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 minimisethese 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.


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7

Major Potential Errors in Critical Care Testing

Post-Analysis Pre-Analysis

Analysis

Patient

PatientTesting Cycle

• Result not reportedor report delayedTranscription errorin written reportNo clinical detailswith resultCritical value nothighlighted

•

•

•

Instrument notcalibrated correctlyInsufficient sampleUnstable precisionof instrumentInterferingsubstances present

•

••

•

Incorrect containerNo or wronganticoagulantWrong patient orwrong identificationExcessive delaybefore analysis

••

•

•

Key Aspects of Quality Management

There are a number of important aspects of quality mana-gement which apply universally to all parts of the criticalcare testing cycle.

Documentation

The involvement of many different people in critical caretesting demands that all procedures are documented in stepby step, easy to understand fashion. Guidelines for whatshould be contained in such documents are available fromaccreditation bodies and the NCCLS. Some laboratorieshave adopted the term Standard Operating Procedure (SOP)for such documents. They should be reviewed regularly andrevised whenever changes are implemented.

Training and Education

Training and education assumes even greater importancewhen testing involves personnel who are not trained labo-ratory professionals. Training needs to be monitored so thatnew staff are incorporated into the program and the pro-gram should be revised as procedures change in responseto the need for quality improvement or the development ofnew 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 internaland 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 thequality planning and improvement process.


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9

Key Aspects of Quality Management

Docu-mentation

Training/Education

Audit/Accreditation

All processesassociated withcritical caretesting shouldbe documented

All staff carryingout critical caretesting shouldreceive regulartraining andeducation

All processesassociated withcritical caretesting shouldbe reviewed byservice usersor externalbodies


10

Chapter I I

Pre-AnalyticalQuality Assurance

Chapter II Pre-Analytical Quality Assurance

11

Steps in Pre-Analytical Quality Assurance

The pre-analytical phase of critical care testing starts withthe request to perform an analysis and finishes with theintroduction of the specimen into the analyser.

The diagram opposite shows that several distinct stagesexist in the pre-analytical process where errors can occurthat will affect the patient result and this may lead to misin-terpretation and incorrect treatment.

While the development of testing nearer the patient hasreduced the time taken to transport specimens to the instru-ment, there remain several manual steps where there is thepotential for significant errors to occur. Thus pre-analyticalvariation in critical care parameters is often greater than ana-lytical variation.

The aim of pre-analytical quality assurance is to remove orminimise 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 errorswhich can occur in the pre-analytical phase. For a moredetailed discussion of pre-analytical quality assurance usersshould consult textbooks on the subject (1, 2), documentsfrom professional bodies such as NCCLS (3-4) or IFCC (5) andthe various references cited in the following pages..

Pre-Analytical Quality Assurance Chapter II

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13

Pre-Analysis

Steps in Pre-Analytical Quality Assurance

Collection Device

Patient Preparation

Sample Transport Anticoagulants

Sample Collection

Sample Site

Seven stepsto

Pre-AnalyticalQuality

Performance of Analysis Request for Analysis

Collection Device or Container

The ideal collection device for blood gas analysis would begas tight, minimise bubble formation during sampling, havea high ratio of volume to surface area and have a plungerthat 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 shownin Figure 1 opposite. In addition they require less heparinand have a low resistance plunger. The disadvantage is thatthey are expensive and inconvenient.

Plastic syringes are inexpensive and disposable. Their dis-advantage is that they are permeable to gases allowing gastensions in the sample to move towards atmospheric pres-sure in the time between sampling and analysis. This is asignificant problem for samples with PO2 values > 150mmHg (Figure 1).

Capillaries are available from Roche in glass or plastic andare useful for neonatal samples from the heal or from theear in the case of adults. However to obtain a clean sample,free of bubbles, requires considerable skill.

The Roche Microsampler is a disposable glass capillarydevice in a plastic container which has the advantages ofglass and plastic devices. From the data shown in Figure 1it can also be seen that the PO2 in an iced microsampler isstable for up to one hour. Data in Figure 1 is from d’Ortho etal (6).


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Collection Device/Container

Advantage:No leakageof gasesLow resistanceplungerDisadvantages:InconvenienceCost

Advantage:ConvenienceCost

Disadvantages:Leakage ofgases(P O2 > 150)

Advantage:Ideal forneonates

Disadvantages:More deman-ding technique

Advantage:ConvenienceNo leakageof gases

Disadvantages:None

GlassSyringe

PlasticSyringe

Glass orPlastic

CapillaryMicro-

sampler

340

350

360

370

380

390

400

Microsampler

Plastic Syringes

Glass Syringes

0 10 20 30 40 50 60 70

Time (mins)

PO

2 (m

mH

g)

Figure 1. Change in PO2 levels with time in Microsamplers,glass & plastic syringes kept at 4° C. Data from d`Ortho et al (6).

▲

▲

▲

▲ ▲

Anticoagulant - which one?

Almost all critical care tests require the sample to be anti-coagulated.

The exception is Coagulation tests which are measured onwhole blood without any anticoagulant or additive. In somecases, coagulation tests may be measured on citrated(sodium citrate) blood but this will interfere with electrolytemeasurements such as sodium and calcium.

The best universal anticoagulant is heparin, usually the lit-hium salt. If this is standard, unbalanced lithium heparinthen the only parameters that cannot be measured on sucha sample are Coagulation tests and Lithium. Alternatives tolithium heparin include the sodium salt but the use of stan-dard, unbalanced sodium heparin means that such samplescannot be used for sodium measurement. Note that Rochemake devices containing specially formulated lithium andsodium heparins which can be used for both lithium andsodium estimations (see page 20).

A number of other common anticoagulants and preservativesare used in the laboratory including flouride oxalate andEDTA, 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 calciumso that an EDTA sample will show a characteristic set ofresults with an undetectable or low ionised calcium and agrossly elevated potassium level.


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17

Anticoagulants – Which one?

NOAnticoagulant

StandardHeparin

Anticoagulant

OtherAnticoagulants

eg EDTA,Oxalate

For allparameters

exceptCoagulation

&Lithium

Only forCoagulation

&Lithium

Should notuse for

anyparameters

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 requiredto anticoagulate a 1ml blood sample and this volume iseasily mixed with the sample.

The main disadvantage of liquid heparin is that it dilutes allthe parameters – 50µl in 1ml corresponds to a 5% dilution.Unfortunately more than this volume is often drawn up intothe syringe and the excess is not evacuated after coatingthe walls of the syringe. In such cases significant dilution ofparameters 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 PCO2 and also bicar-bonate and base excess. The data shown is from Hutchisonet al who also showed that significant errors in diagnosisand treatment could occur from the results obtained onsamples containing excessive heparin (7).

To overcome this problem for those who wish to continueusing liquid heparin, Roche supply a syringe with a limitedvolume of liquid heparin which avoids dilution problems.


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19

Anticoagulants – Which Lithium Heparin?

LiquidHeparin

DryHeparin

Dry,BalancedHeparin

Advantage:Easy to dissolve

Disadvantages:Dilution effectsChelation of ions

Advantage:Avoids dilutionproblems

Disadvantages:Chelation of ions

Advantage:No dilution effectsNo chelation ofions

Disadvantages:None

0

10

20

30

40

50

60

0 10 20 30 40 50 60

% C

hang

e in

PC

O2

% Heparin in Sample

Figure 2. Effects of excess heparin on PCO2 levels.Data from Hutchison et al (7).

Anticoagulant - which Heparin ?

Another solution to overcome the problem with dilution dueto excessive liquid heparin, has been for manufacturers ofcollection devices including Roche, to also supply syringes,capillaries or microsamplers with dry, lyophilised heparinincluded 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, particularlycalcium. Figure 3 opposite shows the decrease in ionisedcalcium levels due to standard dry heparin, which causes asignificant decrease of 0.08 mmol/l in Ca++, even with theminimum anticoagulant requirement of 50µl of standardheparin per ml of sample. Larger amounts of heparin causea corresponding greater decrease in Ca++. Data from Müller-Plathe et al (8).

The problem associated with binding of electrolytes byheparin can be overcome by using a specially formulatedelectrolyte-balanced heparin. Figure 4 opposite shows theionised calcium results from capillaries containing balancedheparin 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 Sachset al (9).

All Roche syringes, capillaries and Microsamplers containelectrolyte-balanced heparin which avoids the problems ofexcessive dilution of all parameters and binding of certainelectrolyte parameters.


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21

0.00

0.05

0.10

0.15

0.20

0.25

0.300 20 40 60 80 100 120 140 160 180 200

0.08

50

Dec

reas

e in

Ion

Ca++

(m

mol

/l)

Heparin (lU/ml)

Figure 3. Effects of unbalanced dry heparin on ionised Ca++ levels.Data from Müller-Plathe et al (8).

0

0.5

1

1.5

2

2.5

3

0 0.5 1 1.5 2 2.5 3

Roch

e ca

pilla

ry Io

n Ca

++ (m

mol

/l)

Reference Ion Ca++ (mmol/l)

% deviation + 0.9 %

% deviation + 6.4 %

% deviation 0 %

% deviation - 2.3 %

Figure 4. Ionised Ca++ levels in balanced heparin capillariescompared to reference levels. Data from Sachs et al (9).

Patient Preparation

Before taking the blood sample consideration should begiven to the clinical condition of the patient.

Relatively steady states in blood gases occur quicker inhealthy individuals than in patients with disease. Thus evenspontaneously breathing patients should rest for 5 minsbefore the blood sample is collected.

Many critical care testing samples are taken from patientswho are receiving treatment. Depending upon the urgencyto make measurements, appropriate times should be allo-wed for a steady state to be achieved after a treatmentchange and before sampling. For example:

• After intubating a patient, allow 20 min beforesampling.

• When weaning a patient from a ventilator, allow10 min before sampling.

Taking an arterial blood sample can be a painful and stres-sful procedure resulting in undue patient anxiety. Thisanxiety can cause hyperventilation and affect the blood gasand pH results. Typical results in such a situation will be alower than expected PCO2 and increased pH. Such results,which are not due to any pathological process, may causemisdiagnosis and the wrong treatment.

Good blood collection techniques by highly trained and skil-led staff can avoid this problem and are discussed in moredetail on Page 26.


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Patient Preparation

Rest TreatmentEquilibrium Anxiety

Spontaneouslybreathingpatientsshould rest5 min beforesampling

Allowappropriatetime aftertreatmentchangesbeforesampling

Avoid painand anxietyto preventeffects onsteady stateof respiration

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 bloodalso has the advantage that its composition does notchange from the aorta to the peripheral circulation. Thus avariety of sites can be used for sampling (see Figure 5) butthe commonest sampling sites are the radial or femoral arte-ries.

In some cases arterialised capillary blood can be used as asubstitute for arterial blood. This is most often used in thecase of premature babies and neonates when the sample isusually taken from the heel. Capillary samples can providesimilar values to arterial blood for all parameters except oxy-genation, where significant differences may exist betweenarterial and capillary PO2. This difference can be reduced byarterialisation or warming the vasculature prior to sampling(see Page 26).

Peripheral venous samples may be used for certain criticalcare 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 PO2 which are usedto calculate additional parameters such as arterio-venousoxygen difference. Mixed venous PO2 requires samplingfrom a catheter in the pulmonary artery.

Repeated sampling from an artery or vein is best providedvia an in-dwelling catheter.


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Sample Site

Most commonsampling site

Can be usedfor all criticalcare para-meters

Often used inneonates

Requiresarterialisationto give correctP O2 results

Used toassess shunts

Peripheralblood notsuitable foroxygenationparameters

Cannulaconvenientfor multiplesamples

Cathetersused for mixedvenoussamples

Artery Capillary Vein Catheter/Cannula

Femoral artery

Figure 5. Preferred sitesof the radial, brachialand femoral arteries forarterial blood sampling

Dorsalis pedis artery

Axilary artery

Brachial artery

Ulnar arteryRadial artery

Sample Site


26

Sample Collection

Collection of blood is a specialised technique which requi-res considerable training and skill. Only the most importantrequirements will be mentioned here and users must con-sult the documented collection procedures in their owninstitution for more details.

The most important requirement is that all samples must becollected in a way that minimises discomfort and trauma tothe patient. This is particularly important in the case of arte-rial samples where access to arterial blood can sometimesbe 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 andachieve a degree of arterialisation. The higher the degree ofarterialisation, the closer should be the agreement betweencapillary and arterial PO2 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 fromthe heel in the case of the neonate or the ear for adults. Forcapillary samples avoiding contamination of the sample withambient air can be difficult but can be facilitated by keepingthe capillary close to the puncture site. When the capillary isfull and depending upon its size, the use of a metal flea maybe required to ensure mixing of the sample with the heparin.

Sampling from peripheral veins should avoid venous occlu-sion for longer than 2 mins.


27

(b)(a)

Sample Collection

Figure 6. Sites of arterialised capillary samplingfrom the ear lobe (a) and the heel (b)

Sample Collection

Artery Capillary Vein

Avoid conta-mination withvenous blood

Requires war-ming to achievearterialisation

Avoid venousocclusion

Avoid conta-mination withflush fluid

Catheter/Cannula

Expel air, Mix, Label

Avoid pain, traumaand contamination with air

Sample Collection

When sampling from an in-dwelling cannula or catheter,care must be taken to ensure that this is purged of flushsolution before sampling blood. Figure 7 shows the effecton haematocrit and pH results when insufficient volume isflushed or discarded before taking a sample for analysis. Theeffect in both cases is significantly lower results due to dilu-tion of the blood with flush solution. The volume that needsto 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 iscomplete, it is vital to dispose of the needle safely accordingto documented procedures.

Air bubbles must be removed from the collection deviceprior to transport. Such bubbles will affect both the PO2 andPCO2 but the effects on PO2 are greater and an example ofthese is shown in Figure 8 opposite. Generally the effectsare proportional to the size of the air bubble and increase inproportion to the length of time that the air bubble is inplace. 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 bubblesimmediately after collection.

Finally it is important to mix the sample to ensure that it isanticoagulated and it must be labelled clearly by hand orwith a barcode containing the patient details.


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29

Page 1

0

5

40

6-8 10-12

Hae

mat

ocri

t

pH

HaematocritpH

35

30

25

20

15

10

7.60

7.40

7.20

7.00

6.80

6.60

6.40

6.20

6.008-104-62-40-2

Figure 7. Effects on pH & Hct of contamination with flush solutionData from Dennis et al (10 ).

Aliquot Volume

True result

0

2

4

6

8

10

12

14

16

18

0 1 2 3 4 5

10 % air bubble

20 % air bubble

% In

crea

se in

PO

2

Figure 8. Effects on PO2 levels of contamination with air.Data from Biswas et al (11).

Time (mins)

Sample Treatment and Transport – Effect on PO2

Many critical care parameters are labile and analysis shouldbe completed as soon as possible after sample collection.

If there is a significant delay in analysis, the major changeswhich 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, fromcells into plasma, leads to spuriously increased potas-sium levels.

Figure 9 opposite shows the effects of metabolism on PO2

levels in samples collected in glass Microsamplers, one groupkept at ambient temperature and the other group kept at 4°C; the original PO2 level was 390 mmHg (50 kPa). The useof glass collection devices minimises any changes in PO2

level due to the diffusion effects which take place in plasticdevices (see Figure 1).

The changes after 15 mins in both samples are not signifi-cant but after 30 mins, the fall in the PO2 levels of uncooledsamples are significant and reflect the metabolism of bloodcells. However these changes can be prevented if thesyringe is cooled with ice.

These metabolic effects are insignificant at PO2 levels below150 mmHg and such samples do not need to be cooled forup to one hour after collection. Data from d’Ortho et al (6).


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31

Sample Treatment & Transport

Ideal situation forall parameters

Insignificantmetabolism andleakage of gases& ions in 15 min.

Also satisfactoryfor all parameters

Cooling preventsmetabolism andleakage of ions.

Unsatisfactory formany parameters

May decrease:pH PO2, Ca, Glu,May increase:PCO2, K, Lac.

Rapid transportbut may cause:

Leakage of ionstrough vibration.Worsen effectof air bubbles

Analysis<15 min

Room TempPneumatic

TubeAnalysis

15 - 60 min4o C

Analysis15 - 60 minRoom Temp

70

75

80

85

90

95

100

105

0 10 20 30 40 50 60 70

Samples at ambienttemperature

Samples cooled with ice

% C

hang

e in

PO

2

Time (mins)

Figure 9. Effects of metabolism on PO2 levels. Data from d´Ortho et al (6).

Sample Treatment and Transport – Effects on Metabolites

The continuing metabolism of blood cells after the samplehas been collected will also affect the levels of metabolitessuch as glucose and lactate.

Figure 10 opposite compares the changes in whole bloodglucose over time in specimens kept at room temperatureand those kept at 4°C. The reductions in glucose levels dueto metabolism are similar at both temperatures and even at60 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 thosekept on ice. Here the changes in the room temperature sam-ples are significant after 30 mins but the resulting increasein 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 FluorideOxalate or Perchlorate to prevent these metabolic changesis not possible because such agents are not compatible withthe sensors used in critical care testing analysers.

In summary the effects of sample treatment and transportupon critical care testing parameters can be minimised byusing the following protocol:

1. Samples analysed within 15 mins can be kept atroom temperature.2. If analysis cannot be carried out within 15 mins.store the sample in iced water and analyse preferablywithin 30 mins but no longer than 60 mins.3. Samples with PO2 levels greater than 200 mmHg(26 kPa) should be collected in glass containers if ana-lysis cannot be completed within 15 mins.


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33

6.3

6.1

OM

NI W

hole

Blo

od G

luco

se (

mm

ol/l

)

5.7

5.55040302010

Figure 10. Effects of metabolism on whole blood glucose levels.

Time (mins)

WB Glucose at 4°C

WB Glucose at RT

6.5

5.9

1

WB Lactate at RT

WB Lactate at 4°C

4030 6020 5010OM

NI W

hole

Blo

od L

acta

te (

mm

ol/l

)

2.6

2.2

1.8

1.4

3

0

Time (mins)

Figure 11. Effects of metabolism on whole blood lactate levels.

Sample Treatment and Transport –Effects of Pneumatic Tube Systems

Transport of laboratory specimens including critical caretesting samples by pneumatic tube systems (PTS) is nowcommonplace. The rapid change in speed of such devicesmeans that they have the potential to affect labile parame-ters such as PO2, 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 specimenswith a PO2 of approximately 60 mmHg (8 kPa) with differentbubble sizes present in the sample compared to Controlspecimens which were walked to the laboratory. Theincrease in PO2 as a result of transport by PTS was onlypartly reduced by the incorporation of a liner or cushionduring transport by the PTS.

Figure 13 shows similar effects but because the specimenshad a higher PO2 (340 mmHg, 44 kaPa) the effect of thebubbles present in the sample and transport by PTS was toreduce the PO2. Once again the liner had no significanteffect but the effects were lessened, by reducing the speedof the PTS by 50%.

The above interferences can largely be eliminated by remo-ving air bubbles from the sample before transport. Howeverusers of PTS need to determine the possible effects onblood specimens before introducing them routinely. Datafrom Astles et al (12).


34


35

0

20

40

60

80

100

120

140

Control PTS no liner PTS with liner

0.50.20

Bubble Size (ml)

PO

2 (m

mH

g)

Figure 12. Effects of pneumatic tube transport (PTS)on PO2 values <100 mmHg. Data from Astles et al (12).

0

50

100

300

350

250

0.50.20

Bubble Size (ml)

PO

2 (m

mH

g)

Figure 13. Effects of pneumatic tube transport (PTS)on PO2 values >300 mmHg. Data from Astles et al (13).

200

150

400PTS with linerControl PTS no liner

Immediate Pre-Analysis

At the time of analysis, sample, patient and ideally, treat-ment (eg F iO2), details must be entered into the instrumentso that a permanent record of identifiable results can be pro-duced, both on the instrument and for transmission to thepatient’s record. This is most easily done via a barcodedlabel on the syringe.

Any air in the sample must be expelled together with anyblood in the luer of the syringe where small clots can oftendevelop.

The sample must be mixed, particularly if the sample hasbeen allowed to stand for any length of time and the bloodcells have started to sediment. Mixing is particularly impor-tant for Hb, Hct and Na parameters. Mixing should be doneby rolling between the hands for at least 15 - 30 sec beforeanalysis 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, hadsignificantly higher PO2 values over time compared toSyringe 2, which required less force on the plunger. Datafrom Gosling et al (13).

Finally when the sample results are obtained from theinstrument, the collection device should be disposed ofaccording to documented health and safety procedures.


36


37

Immediate Pre-Analysis

Enter patientand sampledetails intoinstrument/LIS

Expel airbubblesCheck forclots insyringe luer

Mix sampleto ensurehomogeneityfor Hb, Hctand Na

Avoidexcessiveinjectionpressure orerrors forPO2 and K

EnterPat & Sample

ID

ExpelAir & Clots

MixSample

InjectSlowly

Table 1. Effects of excessive injection pressure on PO2 levels mmHg (kPa).Data from Gosling et al (13).

Syringe 1After 6 min

Syringe 2After 6 min

PCO2 53.1 (6.93)PO2 100.5 (13.12)

PCO2 53.5 (6.98)PO2 97.2 (12.69)

PCO2 52.8 (6.90)PO2 108.0 (14.09)

PCO2 53.6 (7.00)PO2 100.8 (13.16)

After 15 minAfter 15 min

Summary of Pre-Analytical QualityAssurance 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 suppliedwith 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 theinner part being manufactured from glass, it is parti-cularly suitable for samples with high PO2 levels.

• Following collection, the specimen must be labelled,mixed and analysed within 15 minutes.


38


39

Summary of Pre-Analytical Quality Assurance

Seven stepsto

Pre-AnalyticalQuality

Performance of Analysis Request for Analysis

Mix sample andenter patient details

Collect from Radialor Femoral Artery

Avoid air contaminationlabel and mix sample

Analyse samplewithin 15 min

Sample 5-15 minafter treatment

Use Roche Syringe/Capillary/Microsampler

Use balanced heparin


40

Chapter I I I

AnalyticalQuality Assurance

Chapter III Analytical Quality Assurance

41

Aspects of Analytical Quality Assurance

The procedures necessary to achieve analytical quality canbe divided into two groups. The first is Monitoring of Analy-tical Quality often called Quality Control. The majority of thischapter 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 today 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 frequentprocesses, usually organised by an external agency.

The second group of procedures contributing to analyticalquality are termed Control of Analytical Variables and theyinclude

• Selection of the best or most suitable method ormeasurement device.

• Knowledge of the materials used for calibration andtheir 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 areusing instrumentation on a day to day basis, they are no lessimportant, particularly to those people who are responsiblefor the quality of results produced by the instrument. Theywill be explained in more detail on Page 80.

Analytical Quality Assurance Chapter III

42


43

Aspects of Analytical Quality Assurance

Monitoring ofAnalytical Quality

Control ofAnalytical Variables

• Internal Quality Control (IQC)

• External Quality Control (EQC) OR Proficiency Testing

Quality Control • Selection of analytical method

• Calibration materials

• Instrument maintenance

• Inventory control of consumables

• Good manufacturing practice

Quality Control Terminology – Precision & Accuracy

The aim of all quality control procedures is to reduce theerror associated with any analytical process ie high quality isrelated to low error. Various terms are associated withdescribing the quality of analyses but the two most com-monly used are Precision and Accuracy.

One approach to understanding the difference in these twoterms is to use the Target analogy (Diagram opposite). If thearrows or darts are scattered all over the target we candescribe the shooting as neither precise (none hit the sameplace) nor accurate (none hits the centre). If the arrows areall closely grouped but away from the centre we can say thatthe shooting is precise but not accurate. If all the arrows aretogether in the centre then the shooting is both PRECISEand ACCURATE.

In the laboratory we usually consider the quality of an ana-lytical method in terms of how it compares to a previouslyestablished method or reference method which is usually ofhigh quality or associated with low error. The results of pati-ent samples analysed by the established method and by thenew method can be graphically presented as in the DiagramComparing Data.

When the points are scattered either side of the diagonalline the results are not precise and not accurate. When thepoints all lie close to a diagonal line but which is not at a 45°angle then the results are precise but not accurate. If thepoints all lie close to a diagonal line and it lies at a 45° angle,then the results are both precise and accurate.


44


45

Quality Control Terminology -The Target Analogy

• Scattered hits away from target

• Not precise

• Not accurate

• Close hits but away from target

• Precise

• Not accurate

• Close hits all on target

• PRECISE

• ACCURATE

Quality Control Terminology - Comparing Data

• Scattered points on both side of line of identity

• Not precise• Not accurate

• Close points but to one side of line of identity

• Precise• Not accurate

• Close points around line of identity

• PRECISE• ACCURATE

New

Met

hod

Reference Method

New

Met

hod

New

Met

hod

Reference Method Reference Method

Types of Error

Errors associated with analytical methods can be classifiedaccording to two types. Figure 14 shows a similar graphicalplot to that shown on the previous page where twomethods are compared. If there was complete agreementbetween the methods, all the points would lie on the soliddiagonal line or the line of identity.

In reality, complete agreement rarely exists because oferrors in both of the methods. The scatter of points orresults on either side of the line (negative and positive)represents Random Error and the greater the scatter, thehigher the random error or the poorer the precision or repro-ducibility of the result.

Random error is often due to factors such as instability inthe 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, andrepeatability.

Systematic error in a new method produces results whichare either high or low compared to the reference method.From Figure 15 opposite we can see that Systematic Errorcan either be Constant in that it is high or low by the sameamount or it can be Proportional which means that it variesaccording 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 byterms such as Accuracy or Bias.


46


47

New

Glu

cose

Met

hod

Glucose Reference Method

Figure 14. Random error between two glucose methods.

0

5

10

15

20

25

0 5 10 15 20 25

New

Glu

cose

Met

hod

Glucose Reference Method

Figure 15. Different types of systematic error between two glucose methods.

15

25

20

10

105

5

00 15 20 25

No Error

Proportional Error

Constant Error

Concept of Total Error

While it is useful to know the various types of error whichcan affect analytical results, it is most important to know theTotal Error of any particular method. The Total Error repre-sents the sum of all the different errors combined and thefinal analytical quality is dependent upon the Total Error (14).

How Total Error relates to the individual error componentsis illustrated in Figure 16 opposite. The Random Error can berepresented as the distribution of results around a centralmean value. Such a distribution of results would be obtainedif multiple analyses were performed on the same patientsample. The shape of this distribution is a characteristic bell-shaped curve called the Normal Distribution. The larger theRandom Error or the lower the precision, the wider will bethe distribution of results.

The Systematic Error in Figure 16 is represented by the shiftof the central value of the distribution from the True Value.In this example where the errors occur in the same directionit can be seen that the Total Error is larger than either theRandom or the Systematic Errors alone and therefore TotalError gives a more realistic estimate of the analytical quality.


48


49

—X

Figure 16. The total error concept of accuracy (14).

Random Error

Observedvalues

Truevalue

—X µ

Systematic Error

Total Error

µ–

Principles of Control Charts

Quality Control is based on the principles of Control Chartswhich are graphical displays of results for control materialsobtained over time. The values obtained are compared tothe known values for the control materials which are repre-sented by a range of acceptable values called the controllimits.

Calculation of Control limits is described in more detail onPage 58. It is assumed that repeated measurements of thesame sample, or the error distribution of the analyticalmethod, will conform to a Normal or Gaussian Distributionand therefore we can calculate the Control Limits using theMean ± 2 or 3 Standard Deviations (SD). If we use 2 x SDthis will include 95% of all results while 3 x SD will include97.5% of control results.

How different error distributions translate into control chartsis 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 onthe Control Chart below in Figure 18, with all results beingdistributed around the mean value but within the controllimits.

In (b) the distribution shows a shift of values away from themean, indicating a systematic error or accuracy problemwith the method, and this is reflected in control values beingon 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 methodwhich produces a wider distribution of results and on thecontrol chart this is shown as a wider scattering of resultson both sides of the mean value, with some results outsidethe limits.


50


51

a) Stable performance

b) Accuracy problem, shift in mean

c) Precision problem, increase in standard deviation

control limit

control limit

Obs

erve

d C

ontr

ol C

once

ntra

tion

Figure 17. Frequency distribution of different error conditions.

control limit

control limit

Obs

erve

d C

ontr

ol C

once

ntra

tion

Figure 18. Representation of above error conditions as a control chart.

Frequency of Observation

Types of Quality Control

Quality Control procedures can be classified as Internal Qua-lity Control (IQC) or External Quality Control. The latter isoften called External Quality Assessment (EQA) and in theUnited 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 senseIQC is a real-time process. IQC is primarily about the preci-sion or reproducibility of analytical methods and ensuresthat sequential results on the same patient are comparableand of similar quality. This is of obvious importance in thecritically 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 viapatient 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, itusually occurs at intervals varying from once per fortnight toonce per year.

The EQA or PT process involves samples of a stable controlmaterial being distributed by an external agency. Followinganalysis by the laboratory the returned results are proces-sed to allow the retrospective comparison of results fromdifferent laboratories and comparison of all the results to theso-called "True” value.


52


53

Types of Quality Control

Internal QualityControl

External QualityControl

• Real time process

• Used on a day to day basis to determine acceptability of results

• Can use stable control material or patient data

• Organised by the laboratory

• Proficiency testing in USA

• Retrospective process

• Used to compare performance of testing with other laboratories

• Uses stable controls

• Organised by external agencies

Types of Quality Control Materialand Handling Requirements

Aqueous Controls

These are the most widely used and consist of aqueousorganic and carbonate buffers in equilibrium with predeter-mined levels of oxygen, carbon dioxide, nitrogen, electro-lytes and metabolites in solution. Examples are RocheCOMBI-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 thistype 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 bloodgases because it most closely resembles a patient samplebut its major disadvantage is that it requires a specialisedtonometer and carefully calibrated gas mixtures togetherwith a skilled operator.

Handling of QC material

This must be according to the manufacturers’ instructions.• Samples must be stored at the right temperatureand usually brought to room temperature before analysis• Samples must be mixed correctly and excessive agi-tation avoided• Samples should not be excessively warmed beforeanalysis• Samples should be analysed without delay after ope-ning the ampoule.


54


55

Types of Stable Quality Control Material

AqueousControls

FluorocarbonEmulsions

TonometeredBlood

• Human or bovine blood tonometered with defined gas mixtures

• The best material for blood gases

• Disadvantage is the need for special equipment & skills

• Fluoridised organic compounds

• P O2 carrying proprieties more closely resemble blood

• Disadvantage is fluorocarbons poison ISEs

• Buffers equilibrated with gases and containing other analytes

• Most widely used material

• Disadvantage is sensitivity to PO2 contamination

Handling conditions for QC materials

Storage TimingMixing Temperature

Develop a written protocol for QC handling

Read manufacturer´s instructions

Bring materialto RT beforeanalysis ifstored at 4°C

Avoid excessiveagitation beforeanalysis

Avoid excessivewarming beforeanalysis

Analyse immed-iately after vialis open


56

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 inFigure 19 opposite (16).

The presence of haemoglobin in blood and the shape of theoxygen-dissociation curve means that blood has high oxy-gen buffering or resistance to changes in PO2 at low tomoderate levels of PO2. This makes tonometered blood theideal QC material for PO2 measurement but for reasons dis-cussed previously, it is not a practical material on a routinebasis.

In contrast to blood the most widely used aqueous materi-als have very low oxygen solubility in water and thereforethey have no buffering capacity and are very sensitive tochanges in PO2 which can occur if the sample is contami-nated with atmospheric air. The implications of this for PO2

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 PO2 levels.


57

Buffe

r cap

acity

PO2

Figure 19. Oxygen buffering ability of differentcontrol materials at varying PO2 levles.

Water

Fluorocarbon

Blood

How to establish an InternalQuality 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 Rochequality control materials such as COMBI-trol and AUTO-trolare supplied with stated means and ranges of values for par-ticular instruments. These values can immediately be usedto establish a Control Chart for each analyte.

However it is recommended that individual laboratoriescheck that the stated values and ranges are correct by mea-suring the material on their instrument(s) over a minimumperiod of 20 days, followed by calculation of the Mean, Stan-dard Deviation (SD) and Ranges. These values may showslight differences to the stated values but they will more clo-sely reflect the performance of their instrument(s) and theyshould then be used to construct the control chart.

The typical control chart, often called a Levy-Jennings chartis shown in Figure 20 opposite. The concentration of ana-lyte, eg Glucose is on the vertical axis and the Run Numberon the horizontal axis. Additional dotted and hyphenatedlines indicate the allowable limits within which the QCvalues should fall. The dotted lines correspond to the MeanValue ± 2 Standard Deviations (SD) while the hyphenatedline 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 gaseswhere incorrect procedures such as excessive shaking andwarming or delays in analysis after the QC ampoule is ope-ned, can lead to incorrect results. All QC samples should beaspirated into the instrument with an ampoule adapter.


58


59

How to establish a QC programme

Use manufacturer’sstated mean & range

Determine ownmean & range

Select suitableQC material

Construct controlchart with mean

and allowable limits

Analyse andrecord QCs at

specified times

Gluc

ose

(mm

ol/l)

Run Number

Figure 20. Internal QC or Levy-Jennings Control Chart.

6

7

6.5

5

844

0 12 16 20

2 x SD

4.5

3 x SD

5.5

How to use a QC Programme on a daily basis

A protocol for describing how QC is to be performed on adaily basis must specify how often QC samples are to beanalysed. In some countries such as the United States thefrequency of QC analysis is determined by legislation (17).

The most common practice is to analyse QC samples 3times per day, with a different level of QC on each occasion.In addition QC samples should be analysed after any routinemaintenance procedure and after any problems have beenresolved with the instrument.

Following analysis of the QC sample the results are plottedonto the chart and checked to see that they are within thechosen limits, either within 2 SDs or 3 SDs of the mean. Ifthe results are within the chosen limits patient samples canbe analysed.

If the QC result is outside the limits then an Out-of-Controlprocedure 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 toincorrect 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 procedureshould be followed until the fault is found and corrected.

All out-of-control results should be plotted on the charttogether with a comment as to the possible cause and howit was corrected.


60


61

How to use a QC Programme on a daily basis

After anymaintenance

procedure

After anyinstrumentproblems

3 timesper

24 hours

Analyse QCs atspecified

time intervals

Record QCvalues onQC Chart

Analysepatient

samples

Followout-of-control

procedure

QC NOT OKQC OK

Responses to Out-of-Control Situations

Note QC valueRecalibrate

Analyse new QC

Note QC valueTroubleshootInstrument

Note QC valueAnalyse new QC Analyse patient samplesQC OK

QC OK

QC not OK

QC not OK

Analyse patient samples

QC is outside limits

Simple QC limits, Westgard Rules & Roche MultiRules

The most common control rules that are used for internalQC are the 2 SD and 3 SD rules. The 2 SD rule is often regar-ded as a "WARNING” limit because there is a statisticalchance that even when the analytical procedure or instru-ment is working optimally and in control, 1 of 20 results willfall either below or above this limit. Thus, results outside ofthis 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 muchsmaller (1 in 100) and therefore there is a strong possibilitythat this represents a genuine problem which must be inve-stigated.

However these simple rules have limitations in detecting agenuine analytical error ie the 2 SD rule may be too sensi-tive and result in too many repeat QC analyses while the 3SD rule may be insensitive in that it allows problems todevelop before taking action.

As a result of these limitations more sophisticated QC ruleshave been developed by Westgard et al (18) which reduce thenumber of falsely rejected runs and increase the sensitivityof error detection. These rules have been modified for criti-cal care testing analyses according to Elsa et al (19) and havebeen incorporated in the Roche OMNI QC software asRoche Multirules. Users of the OMNI instrument can usethe simple 2 SD Range rule described earlier, either alone orin combination with one or more of the Multirules as shownin Table 2 opposite.


62


63

Gluc

ose

(mm

ol/l)

Run Number


6

7

6.5

5

844

0 12 16 20

2 x SDWarning Limit

4.5 Warning Limit

Action Limit

Action Limit

3 x SD

2 x SD

3 x SD

5.5

Table 2. Roche Multirules based on Westgard Quality Control Rules

12σ • Warning

Rules based on analysis of 3 QC samples of randomlyselected levels per day

13σ

(2of 3)2σ

22σ

61σ

9Mean

• Action

• Action

• Action

• Action

• Action

• QC measurement is outside Mean ± 2 σ

• QC measurement is outside Mean ± 3 σ

• Two of three QC measurements are outside Mean ± 2 σ

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

• 9 QC measurements are all on the same side of Mean

• 6 QC measurements of the same level are outside Mean ± 1 σ

Rule Description Message

Long-term Quality Control Performance – Shift in values

As well as demonstrating QC performance on a day-to-daybasis, the additional value of QC charts is to demonstratemore subtle changes in QC values which may occur over alonger period of time.

Figure 22 opposite shows the printed format of the Levy-Jennings control chart from the Roche OMNI instrumentwhich automatically plots the analysed QC values on thechart against the 1, 2 and SD limits shown as 1s, 2s and 3s.This particular chart shows the daily QC values of CombitrolLevel 2 for glucose between July 24 and August 7, 1999,and the plotted values indicate that the method is in controlaccording to the 2 SD rule discussed earlier.

Figure 23 shows a later situation for the same instrumentand method. In the latter half of September 1999, there wasa relatively sudden shift in values downward so that alt-hough the method appeared precise and the majority ofvalues 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 detectedwhen such changes are recorded, as they should be, in theinstrument log.


64


65

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

2s

X

Combitrol 2 Glucose Lot 312 24.07.99 - 07.08.99

3s

1s

1s

2s

3s

Figure 23. Levy-Jennings Chart showing shift in QC values.

2s

X


3s

1s

1s

2s

3s

Long-term Quality Control Performance – Imprecision and Drift

Figure 24 opposite gives a clear demonstration of methodimprecision with wide variations in QC values on a day-to-day basis. Again, values are almost all within the 3s limit butseveral early and consecutive values are outside the 2s limitwhich indicates that there may be a problem. By the end ofOctober it is clear that the method is not working optimally.

Possible causes for this type of performance are many andthey 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 25where QC values are normally distributed around and closeto the mean value and then start to drift upwards, but gene-rally remaining within the 2s limit. Such a trend may be thefirst sign of an electrode which is coming to the end of itslifetime or deteriorating reagents. By monitoring QC valuesin this way, it is possible to implement a solution to the pro-blem before it starts to adversely affect patient results.


66


67

Figure 24. Levy-Jennings Chart showing imprecision of QC values.

2s

X


3s

1s

1s

2s

3s

Figure 25. Levy-Jennings Chart showing development of drift in QC values.

2s

X


3s

1s

1s

2s

3s

Internal Quality Control using Patient Samples

Although using stable commercial quality control materialsis the mainstay of internal quality control it is also possibleto use the results obtained from patient samples as a meansof 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 aspossible after the first in order to minimise any potential pre-analytical changes. This procedure is particularly useful forblood gases because of the limitations of commercial QCmaterial to assess analytical performance, as discussed ear-lier on Page 56. Such a procedure can be formalised withthe plotting of the difference between the two results on aQC chart with limits for allowable performance based on thestandard deviation of the differences (20).

Another application of patient data to monitor analytical per-formance is to check the results of parameters which arederived from a combination of tests. Examples are AnionGap, Osmolar Gap or HCO3. Anion Gap is calculated from anumber of electrolyte measurements and an incorrect resultfor one of these may produce values for Anion Gap whichcan be seen to be erroneous (21).

Patient means or the mean value of a test derived from largenumbers of patient samples can also be used to monitorquality because for many parameters this value is remarkablystable; significantly different values from previous meanscan indicate that the method is out of control. Howeverwhile there is increasing interest in this form of internalquality control, it is not suitable for many critical care testingparameters (22).


68


69

Internal Quality Control using Patient Samples

DuplicateAnalyses

PatientMeans

• Based on premise that mean of patient result is relatively constant

• Not suitable for critical care testing

• Based on detecting errors when results used to calculate other parameters

• Examples: Anion Gap Osmolar Gap pH and H+

• Same sample analysed on two different instruments

• Rapid analysis required to minimise pre-analytical errors

• Simple QC check

Relationshipwith other

tests

External Quality Assessment or Proficiency Testing

External quality assessment (EQA) or Proficiency Testing(PT) was briefly introduced on Page 52. The aim of EQA isto compare and assess the performance of individual labo-ratories and it is usually conducted by an external agencyon a retrospective basis. The agency is responsible forassigning target values for the material to be analysed, dis-tributing the control material, processing the results andreturning reports to laboratories on their performance.

The design of EQA schemes varies between countries butdesirable 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 PCO2. Individual laboratories arecompared according to the particular instrument they areusing, usually called a Peer Group. Each Peer Group has aTarget Value which is usually the mean of the group and anacceptable range within which individual laboratory resultsmust fall. For PCO2 the means of different groups of instru-ments or peer groups is similar but for other parameters themeans may be significantly different.

Figure 26 shows a graphical presentation of EQA data. Indi-vidual laboratory results for PCO2 are plotted against themedian PCO2 value of all instruments. In this case the idealperformance for an individual laboratory would be to have alltheir results on the central line of identity or within the lineson either side of the central line which indicate the limits ofacceptable performance.

EQA or PT is compulsory in those countries which haveadopted laboratory accreditation or a similar process ofexternal review.


70


71

Table 3. Comparison of PCO2 results obtained as part of Proficiency Testing survey

1

InstrumentGroup

No ofLabs

Mean SD Median Low High

2

3

4

5

6

Total instruments

CV

178

239

88

58

127

219

3410

32.6

32.4

29.8

32.2

31.0

32.2

31.6

1.3

1.4

1.6

1.1

1.6

1.1

1.9

3.9

4.2

5.4

3.4

5.2

3.4

6.0

33

32

30

32

31

32

32

29

27

26

30

27

29

25

36

37

35

35

35

35

39

Labo

rato

ry P

CO

2 Va

lue

(mm

Hg) 70

60

50

40

30

20

1010 706050403020

Median PCO2 Values (mmHg)

▲

▲▲

▲▲

▲

▲▲

▲

▲

Figure 26. Graphical comparison of PCO2 resultsobtained as part of External Quality Assurance survey

Special features of Quality Control on Roche instruments

AUTO QC and QC Consequences

When instruments are located away from direct laboratorysupervision there is the potential for two serious problemsto occur. The first is for QC samples not to be analysed atappropriate times or in some cases not at all. The secondproblem is that QC samples may be analysed, but theresults are ignored and despite indications of an Out-of-Con-trol situation, patient samples are analysed and possiblyincorrect results are reported.

The first problem has been overcome by the AUTO QCmodule which is attached to the OMNI analyser and con-tains QC ampoules of different levels. The AUTO QC can beprogrammed to sample QC samples at specified time inter-vals. Samples are aspirated into the OMNI, analysed and theresults displayed in an identical way to manual QC samples.The status of the AUTO QC is indicated on the OMNI screenas shown in Figure 27 opposite.

As well as ensuring that QC samples are analysed, the othermajor 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 whichcan automatically deactivate parameters when QC resultsviolate either the 2 SD rule or any of the Roche Multirulesdiscussed earlier. Activated or deactivated parameters areclearly 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 theQA 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


73

Figure 27. OMNI screen showing status of AUTO QCdevice and activated or deactivated parameters.

Parameter is Grey.out of QC and auto-matically deactivated

All other parametersare in Green, in QCand automaticallyactivated

Indicates AUTO QCis connected

Remote Quality Management via OMNILink & AUTO QC

The location of diagnostic devices outside of the centrallaboratory and closer to the patient has been termed theBoundaryless Laboratory (24). While this development hasenabled laboratories to provide a much more responsiveservice, many remotely located devices still require regularvisits from laboratory staff for quality assurance purposesand these are time consuming especially when instrumentsare long distances from the laboratory.

To overcome these problems, Roche OMNILink software inconjunction with the AUTO QC module can provide remotequality 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 thehospital network to the OMNLink server in the central labo-ratory.

Via a PC running the OMNILink software, central laboratorystaff can readily see the status of all connected analysersincluding any malfunctions of electrodes, reagent fill levelsand any other errors. The OMNILink Database screen pro-vides a history of all calibration, QC and patient data whilevia the Remote Control screen the operator can take controlof 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 QCsamples can be remotely initiated. This unique combinationof software and hardware has been extensively evaluated (25)

and the benefits of OMNILink are documented opposite.


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Figure 28. Management of remote critical care instruments fromCentral Laboratory using OMNILink software.

Benefits of OMNILink & AUTO QC

AnalyticalQuality

LabourSavings

ServiceQuality

• Problems fixed before users are aware of problem

• Out-of-hours problems more easily fixed

• Selective deactiva- tion of parameters leaves remaining ones available

• QC samples are always analysed

• QC analysis without operator variability

• QC results always interpreted according to set rules & warning indicated

• Daily visits to analyser no longer required

• 90% of problems can be fixed remotely

• Visits to analysers can be planned

Quality control of PO2 measurements

The poor oxygen buffering capabilities of aqueous basedcontrols means that aqueous PO2 measurements are subjectto considerable error (26). This error arises because during thetransport of an aqueous sample from the ampoule to themeasuring chamber, the sample becomes contaminated withroom air, which usually has a much higher PO2 value andthus 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 thesmallest sample volumes, it suffers most from the problemof air contamination of aqueous control samples.

To compensate for this problem on the OMNI instrument, aspecial aqueous mode is available which corrects for conta-mination and gives the most accurate estimate of PO2 inaqueous samples. This is shown in Figure 29 oppositewhich compares the results obtained for an aqueous sam-ple in the Blood and Aqueous modes.

Figure 30 opposite compares the performance of RocheOMNI and OPTI instruments to other unspecified manufac-turers in an EQA or PT Survey using bovine whole blood andaqueous samples. OMNI measurements were in the bloodmode for both materials. Thus the OMNI has a major biasfor aqueous material as discussed above but gives accurateresults for the bovine whole blood material.

Despite the biases that are demonstrated when aqueousmaterials from EQA or PT surveys are measured in theOMNI Blood mode, we continue to recommend that custo-mers use the Blood rather than the Aqueous mode. This isprimarily 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 asFlame Equivalent values, similar to the reference standard.


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1408040

Mea

sure

d P

O2 (

mm

Hg)

200

160

80

0

Target PO2 (mmHg)

Figure 29. Comparison of OMNI Blood and Aqueous modesfor measurement of P O2 in aqueous control solution

40

120

160 2000

Aqueous Mode

Blood Mode

Instrument

OMNI OPTI A B C D E F G H

30

25

20

15

10

5

0

Bia

s (%

)

-5

-10

-15

Aqueous Bias

Tonometrol Bias

Figure 30. Comparison of OMNI and OPTI measurements with other unspecifiedinstruments of PO2 bias in Aqueous and Bovine Whole Blood QC Materials.

Single-use device & Electronic Quality Control

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

The whole area of QC for single-use devices is an evolvingone with a NCCLS Guideline on this topic currently beingdeveloped (27). In the meantime however manufacturershave developed a number of strategies to ensure adequatequality control of single-use devices.

One such strategy is for internal procedural controls to bebuilt into the analytical process. Figure 31 opposite showsthe control lines which appear for negative and positive mea-surements on the Roche TROPT device for measurement ofTroponin T. Such control lines will only appear if the sampleis 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 theinstrument. These include a Sample Reference Cassette(SRC) as shown in Figure 32 compared to a normal patientsample cassette. Three levels of SRC are available and theyare designed with a stable flourescent material which wheninserted into the instrument, checks for noise and drift in theoptics, electronics and temperature of the instrument. Inaddition to the SRCs, the software of the OPTI instrumentincludes many other fail-safe electronic checks, which areperformed with every sample measurement.

A formal evaluation of the electronic QC strategy of theOPTI analyser found that it conformed with the require-ments of the US CLIA’88 regulations (28).


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In-built negative and positivecontrols for TROPT

Figure 31. In-built negative and positive controls for Roche TROPT device

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 32. SRC or Standard reference cassette at frontcompared to a normal patient cassette behind.

SRC cassette

Control of Analytical Variables

Achieving analytical quality is dependent upon controlling anumber of other analytical variables other than those whichare monitored through quality control procedures.

They start with selection of the best or most suitable methodor measurement device. Evaluation is a critical part of this pro-cess but it is important that the assessment of any device isperformed under conditions which reflect the routine situationand involve those people who will be using the instrument.

The quality of any analytical procedure is highly dependentupon the materials used to calibrate or standardise themethod or device. Wherever possible all Roche critical caretesting parameters are calibrated on solutions which are tra-ceable to standards from the National Institute of Standardsin 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 acontinuous supply of reagents and other consumables, withminimal changes in batch numbers and stored under therecommended conditions.

Finally analytical quality is dependent upon the manufactu-rer supplying devices and consumables which have met allthe requirements of Good Manufacturing Practices such astraceability of components and constituents, quality controlof components and manufacturing processes, documenta-tion, conformity to safety requirements, proper labeling andpacking, and adequate product information.

More details about control of analytical variables can befound in a laboratory textbook such as Tietz (1).


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Control of Analytical Variables

MethodSelection/Evaluation

InstrumentMaintenance

GoodManufacturing

Practice

CalibratorMaterials

InventoryControl of

Consumables

• Evaluate method under routine conditions

• Carry out on a regular & documented basis

• Maintaining quality of device & consumables

• Major determinant of method reliability

• Maintain supply and storage conditions


82

Chapter IV

Post-AnalyticalQuality Assurance

Chapter IV Post-Analytical Quality Assurance

83

Stages in Post-Analytical Quality Assurance

The post-analytical phase of critical care testing starts withthe data or patient results produced by the analytical deviceand is completed when the analytical results, together withother relevant and useful information, is reported to the per-son responsible for looking after the patient and into thepatient’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 thepatient such as demographics, clinical history and treatment.

The second stage is comparing the analytical results withappropriate reference values. For some parameters there isalso a need to indicate or "flag” when the patient valuesreach 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 canassist the clinician or nurse with the interpretation of theresults.

The final stage of the post-analytical phase is reporting ofthe data and accompanying information. First this has to bein an appropriate time frame or turnaround time, which forsome critical parameters, may be in a matter of minutes.Second the data and information has to be reported into thepatient’s record or at least to a location where a permanentrecord will exist.

The post-analytical phase of critical care testing is becomingmore important as laboratories and manufacturers now rea-lise that their responsibilities lie beyond providing accurateand precise analytical data.

Post-Analytical Quality Assurance Chapter IV

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85

Stages in Post-Analytical Quality Assurance

Steps toPost-Analytical

Quality

Patient Record Analytical Data

Reporting/Trans-mission of information

to medical record

Integration of datawith patient/treatment

information

Interpretationof data

Comparison of datawith critical values

Combining patient information with data

It is obviously essential that any analytical data or patientresult produced by critical care instruments can be used ina clinically meaningful way so that it contributes to patientcare. This is rarely possible and indeed potentially dange-rous if only the numerical result is reported.

The upper diagram opposite contains a suggested list ofinformation which should accompany a patient result. It isbased largely on the information that is supplied with dataproduced in the central laboratory and a similar datasetshould ideally accompany critical care testing data producedat the point of care (29).

Perhaps the most important piece of information thatshould accompany the result is the Patient ID or Identifica-tion. This should really be part of the Pre-Analytical Phase oftesting (see pages 28 and 36) but it is mentioned here againif only to stress its importance to the testing process.Clearly such identification is obligatory in the case of patientdata which is sent electronically to another informationsystem for reporting of the results and for billing purposes.However patient identification is also advisable even whendata is only stored in the database of the analytical instrument.

In relation to the other ideal requirements shown in theupper 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 areshown in the lower diagram.

The OMNI instrument has the largest and most compre-hensive range of input parameters some of which can alsobe entered via a barcode wand. For the Compact and OPTIinstruments, the parameters must be entered via the key-board.


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87

Ideal Minimum Dataset

Patient Sample Test

• Patient ID• Patient demographics• Clinical diagnosis• Clinical reason for testing

• Sample ID• Date & time of collection• Type of specimen• Date & time of analysis

• Analytical test• Numerical or qualitative result• Reference range• Derived values

Input Parameters

Compact OMNI OPTI

Patient IDPatient SexPatient TempTotal HbHb TypeP50Resp. QuotientFiO2

Patient IDPatient NamePatient Sex & AgePatient TempSample NumberSample Time/DateSample TypeReporting Time/DateDept. & LocationTotal Hb & Hb TypeP50Resp. QuotientFiO2Ventilator Settings

Patient IDPatient Sex & AgePatient TempSample TypeTotal HbHb TypeP50Resp. QuotientFiO2Ventilator Settings

Reference and Critical or Panic Values

The need to accompany a patient result with the appropriatereference range is obvious and should not need empha-sising. The difficulties of deriving reference ranges for manycritical care parameters means that most laboratories useranges 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, criticalresults can immediately be brought to the attention ofwhoever is looking after the patient.

In those situations where the instrument is in the laboratory,the person responsible for the analysis should alert thedoctor or nurse by telephone or possibly by e-mail. Directelectronic communication makes the task of reportingurgent results much easier.

Reference to the literature shows that the list of criticalvalues goes beyond those available on the OMNI instru-ment, the most critical of which are shown in the diagramopposite. Although the reference source for the abovevalues has been identified, the primary source for thesevalues is not always clear. Laboratories are recommendedto discuss these values with the physicians in their institu-tion before routine application.

As well as highlighting critical values on the report producedby the instrument, laboratories should also consider similar"flagging” on the information system to which the instru-ment may be connected.


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Table 4. Critical or “Panic” values for certain critical care parameters.

Analyte SI Units Conventional Units

pH or H+ <24 or >62 nmol/l <7.20 or >7.60

PCO2

PO2

Na+

K+

Ca++

Glu

tHb

<2.7 or >9.3 kPa

<5.3 kPa

<120 or >160 mmol/l

<2.8 or >6.2 mmol/l

<0.82 or >1.55 mmol/l

<2.2 or >25 mmol/l

<70 or >200 mmol/l

<20 or >70 mmHg

<40 mmHg

<120 or >160 mmol/l

<2.8 or >6.2 mmol/l

<3.28 or >6.20 mg/dl

<40 or >450 mg/dl

<7.0 or >20 mg/dl

Interpretation of data

Interpretation of data falls into two categories. The firstinvolves deciding whether a clinically significant change hastaken place in a parameter since it was last measured. Suchsituations are common in the critically ill where parametersare repeatedly measured in order to monitor treatment.

Whether a significant change has occurred depends uponthe analytical precision of the measurement. For examplethe precision (SD) of ionised calcium measurements is 0.05mmol/l at 1.2 mmol/l. So a result must lie outside of therange 1.10 to 1.20 (1.2 ± 2.0 SD or ± 0.10) for there to be a95% chance that it is significantly different.

The second interpretative situation is the process of makinga clinical diagnosis from one or several values. Correct inter-pretation is often dependent on knowing the clinical historyof the patient and in particular any treatment that they mightbe receiving.

Interpretation of acid-base results can be difficult but thealgorithms shown in the Figures 33 and 34 opposite are rela-tively simple since they use only 3 parameters, pH, PCO2

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 assistanceto deal with the growing amount of data and informationthat they have to process on a daily basis.


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91

HCO3-

PCO2

pH < 7.35 (acidaemia)Metabolic acidosis

Acute respiratory acidosis

Chronic respiratory acidosis

Incompatible

Incompatiblenormal/high

normal/high

normal HCO3-

HCO3-

normal

high2. Mixed metabolic & respiratory acidosis

1. Metabolic acidosis

Figure 33. Diagnostic algorithm for interpretation of a low pH value.

low

low

Mixed metabolic &respiratory acidosis

high

low

low

HCO3-

PCO2

pH > 7.45 (alkalaemia)Metabolic alkalosis

Acute respiratory alkalosis

Chronic respiratory alkalosis

Incompatible

Incompatiblenormal/low

normal/low

normal HCO3-

HCO3-

normal

low

high

high

high

low

2. Mixed metabolic & respiratory alkalosis.

1. Metabolic alkalosis

Mixed metabolic & respiratory alkalosiscardiopulmonary arrestrespiratory failure with anoxia

Figure 34. Diagnostic algorithm for interpretation of a high pH value.

high

Turnaround Times

An important aspect of post-analytical quality assurance isto provide patient results and related information within anappropriate time interval after collection of the specimen,the so-called Turnaround Time. There are various definitionsof Turnaround Time (see Figure 35 opposite) but one defini-tion is the time between collection of the sample and thedelivery 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 beup to several hours. However for critically ill patients, theresults for some parameters are needed within minutes ofthe sample being collected. The need for Turnaround Timesin minutes is one of the driving forces behind Point-of-CareTesting (POCT). Placement of devices directly in CriticalCare Units and other clinical areas greatly reduces the timetaken to transport specimens to laboratories and avoids thedelays than can happen within the laboratory itself.

An alternative to the placement of instruments in clinicalareas is the use of Pneumatic Transport Systems to rapidlytransport specimens from critical areas to the laboratory.Users of such systems should be aware of the possibleeffects on the specimen (see page 34).

No matter where the actual testing is located it remainsimportant for laboratories to monitor periodically the tur-naround time for key parameters. If such times do not meetthe needs of users then steps have to be taken to improvethe situation through an appropriate quality planning andimplementation strategy.


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Laboratory Turnaround Time

Figure 35. Turnaround times associated with laboratory testingand potential reductions achieved with Point of Care Testing.

LaboratoryTesting

SpecimenCollected

TestRequest

TestRequest

SpecimenCollected

ClinicianreceivesInform-

ation

PatientTreated

PatientTreatedPOCT

ClinicianreceivesInform-

ation

POCT reducesTurnaround Time

Reporting of data and information

It is clear that rapid analysis of a patient sample is pointlessif the result does not reach the person who needs that infor-mation to manage and treat the patient. Furthermore theanalytical result together with other relevant informationshould be carried forward into the patient record.

However at the present time it is likely that many patientresults from both small and large measurement devices arenot recorded permanently or in hard-copy form. Of thoseresults that are recorded, this is only achieved by manualtranscription of results which is subject to error. Thus thegeneral situation of reporting critical care testing data isrepresented 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. Thetask of reporting data promptly and accurately can be greatlyfacilitated by linking devices to various types of informationsystems. Up to now this has not been an easy task due tothe 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 2001and already, Roche data management systems are CICcompatible.

With easy connectivity, it is possible to achieve the situationshown in the lower half of Figure 36, whereby data can bereliably transmitted and reported to a variety of differentlocations 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 accessibleform, all patient data.


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95

Manual and often unreliable reporting

Electronic, automated, reliable reporting

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No Hardcopyof Results

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Electroniccapture

& storageof results

BedsideMonitor

ElectronicPatientRecord

Figure 36. Possible ways to report patient data and information

Accessto data

via internet


96

Chapter V

Management of testing outside

the laboratory

Chapter V Management of testing outside the laboratory

97

Management of testing outside the laboratory

Two major factors are responsible for the trend towardsPoint-of-Care, Near Patient or Decentralised Testing. Thefirst is changing clinical practice which includes both theneed for more rapid testing and the move towards ambulantcare 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 theliterature, other factors apart from these driving forces, arerequired for testing outside of the laboratory to be a successand deliver the intended improvements in patient care (35).To help address the challenges associated with this type ofdiagnostic testing various professional bodies from differentcountries have produced guidelines which document requi-rements and provide useful advice for all those embarkingon, or extending their diagnostic services outside of thelaboratory (36 - 38).

These broad guidelines can be modified to take account oflocal knowledge and requirements, gained through consul-tation with all the parties involved, including clinicians, para-medical staff and laboratory professionals. The end-resultshould be a well-defined policy or local guideline whichdetermines all the necessary practices to achieve effectivediagnostic 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 suchtesting within the accreditation system (39) and it is likely thatmany laboratories will move to voluntary and then manda-tory accreditation of their complete diagnostic service, nomatter where it is located.

Management of testing outside the laboratory Chapter V

98


99

LocalRequirements

ProfessionalGuidelines

LocalGuidelines

Voluntary Accreditation

Mandatory Accreditation

Management of testing outside the laboratory

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 nodifferent from those that take place in the central laboratory.Wherever testing takes place the overall goal must be todeliver a quality service.

However the emphasis of a management policy for Point-of-care or Near Patient Testing has to reflect two importantfactors. The first is that testing is often being carried out bynon-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 POCTCommittee which includes all the interested parties andensures a cooperative approach.

Documentation of staffing and direction should clearly statewho is the director and who is accountable for the variousaspects of the service.

Devices and equipment must be appropriate to the task, ina safe and workable environment, and maintained accordingto the manufacturer’s instructions.

The involvement of non-laboratory staff means that staffdevelopment and education takes on an extra importance aswas 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 simpleand concise so that users readily adopt the necessary skillsand techniques.

Management of testing outside the laboratory Chapter V

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101

Local guidelines for testing outside the laboratory

Organisation &Management

Facilities &Equipment

StaffDevelopment& Education

Staffing &Direction

Policies &Procedures

• Strategy, scope & management of provider unit

• Appropriate equipment in sufficient space & a safe environment

• Documented training program for all staff

• Written procedures for sample handling device operation & result handling

• Designated director with lines of accountability for all staff

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: Specimencollection, 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 andelectrolytes. 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. Submittedfor publication 2000.

7. Hutchison AS, Ralston SH, Dryburgh FJ et al. Too much heparin: possible source of error in blood gas analysis. BMJ1983; 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.

Quality Assurance & Critical Care Testing References

102

10. Dennis RC, Ng R, Yeston NS et al. Effect of sample dilutionson arterial blood gas determinations. Crit Care Med 1985; 13: 1067 - 8.

11. Biswas CK, Ramos JM, Agroyannis B et al. Blood gasanalysis: 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 PO2 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. pp384 - 418. Saunders 3rd ed. Philadelphia, USA 1999.

16. Burnett RW. Current issues in quality control and proficiencytesting for blood gases and electrolytes. Quality control inthe clinical laboratory ’95. Eds Ohba Y, Kanno T, Okabe H etal. 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 Shewhartchart for quality control in clinical chemistry. Clin Chem 1981; 27: 493 - 501.

19. Elsa F, Quam BS, Lorene K et al. A comprehensive statisticalquality control program for blood gas analysers. J Med Tech1985; 2.

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20. Bokelund H, Winkel P, Statland BE. Use of randomised duplicates to evaluate sources of analytical error. Clin Chem1974; 20: 1507 - 12.

21. Cembrowski GS, Westgard JO, Lyama-Kurtycz DF. Use ofanion gap for the quality control of electrolyte analysers. Am J Clin Path 1983; 79: 688 - 96.

22. Cembrowski GS, Chandler EP, Westgard JO. Assessmentof "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 froma 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 PO2. Chest 1988; 94: 49 - 54.

27. NCCLS. Quality management for unit-use testing; Proposedguideline. Document EP18-P. ISBN 1-56238-391-4. Wayne,PA, USA: NCCLS 1999.

28. Lassig R, Ehrmeyer S, Tusa JT. The role of electronic controlsin an alternative quality control paradigm under CLIA’88 in the US pp 502 Proceedings of the XVI International Congressof Clinical Biochemistry. 1996 Association of Clinical Biochemists, Cambridge, UK.

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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 AACCPress, 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 ClinBiochem 2000; 37: 241 - 3.

References Quality Assurance & Critical Care Testing

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List of figures & tables

Figure 1. Change in PO2 levels with time in microsamplers, glass & plastic syringes kept at 4°c.

Figure 2. Effects of excess heparin on PCO2 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 PO2 levels of contamination with air.

Figure 9. Effects of metabolism on PO2 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 PO2

values <100 mmHg.

Figure 13. Effects of pneumatic tube transport (PTS) on PO2

values >300 mmHg.

Table 1. Effects of excessive injection pressure on PO2

levels.

Quality Assurance & Critical Care Testing Figures & tables

106

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 controlchart.

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 PCO2

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.

Figures & tables Quality Assurance & Critical Care Testing

107

Figure 29. Measurement of PO2 in aqueous materials using theRoche OMNI.

Figure 30. Comparison of PO2 measurements in aqueous and bovine materials.

Figure 31. In-built negative & positive controls of Roche TROPTstrip.

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.

Quality Assurance & Critical Care Testing Figures & tables

108

Index

Accreditation 8, 98Accuracy 44Air bubbles 28, 36Analytical variables, control of 80Anticoagulants -

Heparin 16EDTA 16Flouride-Oxalate 16

Arterial sample collection 24Auto QC 72, 74

Capillary sample collection 26Catheter or cannula samples 28Collection devices or containers 14Control charts 50, 58 - 67Control materials –

Types 54Handling requirements 54Oxygen buffering characteristics 56

Critical or panic values 88

Documentation 8, 100

Electronic or single-use device QC 78Error –

Types in critical care testing 6Constant ,systematic and total error 46 - 49

External quality control or assessment 70

Glucose –Effect of sample transport 32

Heparin -Liquid 18Dry 20Balanced 20

Index Quality Assurance & Critical Care Testing

109

Ionised calcium, effect of heparin 20Internal quality control –

Using control materials 58 - 67Using patient samples 68

Interpretation of data 90

Lactate, effect of sample transport 32

Management of testing outside the laboratory 98 - 101Microsampler 14Mixed venous sample collection 24

OMNILink & AutoQC 74Out-of-control procedures 60

Patient -Identification 27-28, 86Information, input parameters 86Preparation 22Testing cycle 4

PCO2, effect of excess heparin 18PO2 –

Effect of air bubbles 28Effect of metabolism 30Glass vs plastic syringes 14Buffering capacity of different control materials 56Performance in external QC surveys 76

Pneumatic tube systems 34Point-of-care testing guidelines 98 - 101Precision 44Proficiency testing 70

Quality assurance, definition 2Quality control -

External 52, 70Internal 52, 58

Monitoring of analytical quality 42Quality management 8

Quality Assurance & Critical Care Testing Index

110

Reporting of data & information 94

Sample –Container 14Collection 26, 28Injection 36Mixing 28, 36Treatment & transport 30 - 35

Sample site –Arterial 24Capillary 24Venous 24

Syringes, glass & plastic 14

Total quality management 2Training & education 8, 100Turnaround times 92

Westgard Rules 62

Index Quality Assurance & Critical Care Testing

111

Quality Assurance & Critical Care Testing Chapter V

112

Roche Diagnostics GmbHSandhoferstr. 116D-68305 Mannheim/Germany

Tel. +49 - 621 - 7590Fax +49 - 621 759 2902

3

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ISBN 3-88630-250-4

www.roche.com/poc

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Critical Care TestingQuality AssuranceThis book describes the various quality assuranceprocedures at all stages in the patient testingcycle and how they contribute towards obtainingthe correct patient result.

Critical Care Testing - Quality Assurance

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