Blood Gas and Critical Care Analyte Analysis: Chapter Objectives

Download as pdf or txt
Download as pdf or txt
You are on page 1of 24

© VikaSuh/ShutterStock, Inc.

Chapter

6
Blood Gas and Critical Care
Analyte Analysis
Maria Delost

CHAPTER OBJECTIVES point of care (POC) in critical care areas such as the
emergency department, neonatal and adult medical
1. List the types of samples that can be analyzed for blood
gas and analyte concentrations.
intensive care units, surgical intensive care units, and
2. Describe the three phases of analysis. the operating room.2
3. Explain the types of errors that can occur with blood gas The collection and analysis by portable or standard
analysis. blood gas machines at or near the point of care mini-
4. Calculate oxygen content. mizes the time needed to obtain and report laboratory
5. Define Westgard rules.
6. Distinguish between shift and drift.
values, which facilitates timely evaluation of results and
7. Describe the QC process for a point-of-care testing device. prompt intervention.3 Although the basic principles of
operation for blood gas analyzers haven’t changed signif-
KEY TERMS icantly from earlier units, the components were notably
adapted in 2005. At that time, self-contained cartridges
Acid Electrochemical cell
Amperometry Electrode were introduced into several analytical systems, pav-
Analyte Oxidation ing the way for point-of-care testing and compact units.
Anode Partial pressure of oxygen During this innovative period, additional analytes were
Base (pO2) incorporated into the testing menus. Today, healthcare
Buffer Potentiometric
facilities have the option of selecting analyzers to meet a
Cathode Pulse oximetry
CO oximetry Reduction variety of clinical needs and testing menus.4
Early blood gas analyzers were high maintenance
and temperamental instruments that required oper-
Introduction ator-generated maintenance, calibration, and quality
Blood gas analysis provides critical information to control. These units only measured the pH, partial
healthcare providers that assists in the diagnosis and pressure of oxygen (pO2), and partial pressure of carbon
treatment of a variety of metabolic and respiratory dioxide (pCO2) and provided calculated or derived val-
disorders. Historically, clinical laboratory testing was ues for other parameters. Today, auto-calibration and
performed by medical laboratory scientists and medical verification modes provide a more predictable testing
laboratory technicians. Today, blood gas analysis is atmosphere for the measurement of pH, pO2, pCO2,
performed by trained personnel not only in the central hemoglobin, electrolytes, and metabolites such as glu-
or core laboratory, but by respiratory therapists1 in cose, lactate, and creatinine.5 Of course, calibration
satellite laboratories or with portable devices at the and quality control remain paramount in the accurate

151

9781449601942_CH06_PASS02.indd 151 01/10/14 6:44 PM


152 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

measurement and reporting of all values obtained from subject to variables that are not accounted for, contrib-
blood gas analyzers. uting to error.
Percutaneous arterial puncture or arterial sampling
from an indwelling catheter with measurement by a
point of care or standard analyzer remains the “gold Common Abbreviating Symbols
standard” for analysis. Fiber-optic catheters may be and Acronyms
used for invasive in vivo analysis of pH, pCO2, and pO2.
Symbols for electrolytes and analytes are summarized
The indwelling catheters and analysis system allow
in Table 6-1. The testing of these analytes is described
for continuous blood gas monitoring with minimal
later in the chapter. Table 6-3 summarizes common
blood loss.6 Continuous monitoring of pCO2, pO2,
symbols and acronyms used in blood gas testing.
and oxygen saturation can be accomplished through
noninvasive methods by transcutaneous monitors and
pulse oximeters, respectively. Noninvasive methods Specimen Type and
involve minimal risk to the patient and require no spec-
imen; a continuous measurement is obtained by placing Origin Symbols
electrodes or probes on the body. Blood gases can be analyzed on a variety of specimen
types, including arterial, venous, and capillary samples.
The collection site is based on the patient’s diagnostic
Common Nomenclature for Blood needs and clinical condition. In general, collection
Gases and Analytes of an arterial specimen by percutaneous puncture or
Nomenclature and reference ranges for analytes and indwelling catheter is recommended. Heparin is the
arterial blood gas parameters are summarized in preferred anticoagulant used in the syringe for speci-
Tables 6-1 and 6-2, respectively. Reference ranges may men collection.8,9 Venous specimens may be suitable if
vary slightly and are based on the methodology, age of pH, pCO2, and bicarbonate values are needed. Results
the patient, and reference values the particular health- from venous specimens are affected by metabolism and
care facility adopts.7 The reference ranges listed in this peripheral circulation. Arterialized capillary samples
chapter are a guide. Blood gas instruments directly can be collected from the earlobe, finger, toe, or heel.
measure the pH, pO2, and pCO2; other parameters, When collecting capillary blood from the heel, the site
such as the bicarbonate, oxygen saturation, and base should first be massaged or carefully warmed. Heel col-
excess, are derived or calculated values. Direct mea- lection is not suitable once an infant has reached 2 to 3
surements are more accurate and reliable; the param- months of age. Capillary specimens are collected into
eters automatically calculated by the analyzer may be heparinized micro-collection tubes.

TABLE 6-1
Analyte Nomenclature and Symbols

Analyte Symbol Reference Range Comments

Potassium K+ 3.5–5.1 mmol/L Major intracellular cation

Sodium Na+ 136–145 mmol/L Major extracellular cation; important in maintaining osmotic pressure

Chloride Cl– 98–107 mmol/L Major extracellular anion

Calcium Ca2+ 8.8–10.2 mg/dL (total) Occurs in three forms: bound to plasma proteins, complexed with ions
such as bicarbonate, and ionized or free, which is the physiologically
active form

Magnesium Mg2+ 1.6–2.6 mg/dL Role in many cellular enzymes for metabolism

Glucose 75–105 mg/dL Increased in hyperglycemia and diabetes mellitus; decreased values
termed hypoglycemia

Creatinine 0.5–1.5 mg/dL Index of renal function and glomerular filtration

Blood urea nitrogen BUN 6–20 mg/dL Major nitrogen-containing end product of protein metabolism

Lactate 4.5–14.5 mg/dL Lactic acidosis may be hypoxic (shock, hypovolemia) or metabolic
(venous plasma) (diabetes mellitus, hepatic disease, neoplasms)
< 11.3 mg/dL (arterial
blood in heparin)

9781449601942_CH06_PASS02.indd 152 01/10/14 6:44 PM


Introduction to General Measurement Concepts 153

TABLE 6-2
Nomenclature and Symbols for Arterial Blood Gas Parameters

Reference
Parameter Description Range Comments

pH Negative logarithm of the hydrogen ion 7.35–7.45 Direct measure by pH (Sanz) electrode
concentration; measure of acid–base
balance of blood.

pO2 Partial pressure of oxygen in arterial 80–110 mm Hg Direct measure by pO2 (Clark) electrode
blood. Also written as paO2.

pCO2 Partial pressure of carbon dioxide in 35–55 mm Hg Direct measure by pCO2 (Stowe-Severinghaus)
arterial blood; mainly regulated by electrode
respiratory system. Also written as
paCO2.

HCO3 Bicarbonate; includes true bicarbonate, 21–28 mmol/L Actual bicarbonate is a derived measurement
bicarbonate, and dissolved free CO2. serum; calculated from the pH and pCO2 of an aerobically
18–23 mmol/L drawn arterial specimen. Standard bicarbonate is
arterial derived from the Henderson-Hasselbalch equation
and indicates the bicarbonate level in an oxygenated
plasma specimen at 98.6°F (37°C) and pCO2 of
40 mm Hg.

sO2 Oxygen saturation of hemoglobin 95–100% Derived value calculated using sO2% = cO2Hb/(cO2Hb
+ cHHb) × 100.
Calculated value does not account for other
hemoglobins or actual pCO2.
Oxyhemoglobin is directly measured using oximetry.

P50 pO2 at which hemoglobin is 50% Calculated parameter


saturated with oxygen.

Buffer base Total of all anionic buffers in the blood; 44–48 mmol/L Calculated parameter; should not be affected by
includes hemoglobin, bicarbonate, respiratory disorders.
inorganic phosphate, and proteins with a
negative charge.

Base excess Number of millimoles of strong acid Calculated parameter; should not be affected by
needed to titrate a blood sample to pH respiratory disorders.
7.4 at pCO2 40 mm Hg.

cHHb = content of deoxygenated hemoglobin; cO2Hb = content of oxygenated hemoglobin

Introduction to General pO2 refers to the partial pressure or tension of


oxygen; it may also be written as PO2 , PO2 , and
Measurement Concepts pO2.The reference range of pO2 in arterial blood is
Gas Tension 80–110 mmol/L. pCO2 refers to the partial pressure
Gas tension is the partial pressure of a gas in blood. or tension of carbon dioxide; it may also be written as
Partial pressure refers to the pressure exerted by a PCO2 , PCO2 , or pCO2 . The reference range of pCO2
single gas in a mixture of gases or in a liquid. The pres- for arterial blood is 35–45 mm Hg.
sure of the gas is related to the concentration of the
gas to the total pressure of the mixture. For example,
the concentration of oxygen in the atmosphere is 0.21. pH
Atmospheric pressure is 760 mm Hg (at sea level). The The pH is a measure of the acidity or alkalinity of a
partial pressure of oxygen in the atmosphere can be solution and ranges from 1–14. Values less than 7.0
calculated by multiplying the concentration of this gas are acidic and greater than 7.0 are alkaline. An acid
in the atmosphere (0.21) by atmospheric pressure is a substance that produces or donates hydrogen
(760 mm Hg).10 ions [H+] when dissolved in water, whereas a base or
alkaline substance is one that produces or donates
Gas tension of oxygen in the atmosphere =
hydroxyl ions [OH–] when dissolved in water. When
0.21 × 760 mm Hg = 160 mm Hg
there are equal numbers of [H+] and [OH–] ions, the

9781449601942_CH06_PASS02.indd 153 01/10/14 6:44 PM


154 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

TABLE 6-3
Common Symbols and Acronyms Related to Blood Gas Testing

Symbol Meaning

pO2 Partial pressure of oxygen; also written as PO2, pO2, or PO2

pCO2 Partial pressure of carbon dioxide; also written as PCO2, pCO2, or PCO2

[H+] Hydrogen ion concentration

[OH–] Hydroxyl ion concentration

Hb Hemoglobin

COHb Carboxyhemoglobin

HHb Reduced or deoxygenated hemoglobin

O2Hb Oxygenated hemoglobin or oxyhemoglobin

THb Total hemoglobin

sO2 Oxygen saturation of hemoglobin

P50 pO2 at which 50% of hemoglobin is saturated

ctO2 Oxygen content

QA Quality assurance

QC Quality control

solution is neutral and the pH is 7.0, as shown in the cell or electrode has a glass membrane with layers of
following equation:10 hydrated and nonhydrated glass. It is permeable or
sensitive to hydrogen [H+] ions. This measurement elec-
H+ + OH– H2O
trode consists of silver-silver chloride (Ag-AgCl), which
is then placed into a phosphate buffer of pH 6.840, and
+
Relationship Between pH and H thus has a known [H+] concentration. The reference half
The pH is the negative logarithm of the hydrogen ion cell or electrode consists of mercury and mercurous
concentration [H+] in moles/liter. For example, a pH chloride (Hg-HgCl) or calomel. This calomel electrode
of 6, a slightly acidic solution, would have an [H+] of is placed into a solution of saturated KCl.11
1.0 × 10 –6. Conversely, if a solution has an [H+] concen- The reference electrode provides steady voltage while
tration of 1 × 10 –12, the pH of this solution would be 12, the measuring electrode responds to the ions of interest
which is very alkaline. in the sample. Thus, the reference electrode provides
The pH is measured in arterial blood to determine a baseline voltage against which the voltage measured
the degree of acidity or alkalinity. The acid–base bal- by the measuring electrode is compared. A pH meter
ance of body fluids, including blood, is maintained or voltmeter measures this potential difference, known
through the hydrogen ion concentration. The reference as ΔE, between the two electrodes. This relationship is
range for the pH of arterial blood is 7.35–7.45.10 Buffers shown in the following equation:
are weak acids or bases that resist changes in pH when ΔE = ΔE0 + 0.05916/n log a1 at 25°C
a strong acid or base is added. The body has several
buffering mechanisms. where:

ΔE = Potential difference
Sensors and Measurement ΔE0 = Standard potential of electrochemical cell
Concepts n = charge of analyte ion
pH Electrode and Reference Electrode a1 = activity of ion

Glass electrodes are commonly used to measure pH. There is a change of + 59.16 millivolts (mV) at 25°C for
The pH measurement system uses the Sanz electrode, a 10-fold increase in [H+] activity and a decrease in
which consists of two half cells connected by a potas- pH units. At 37°C, the change in one pH unit causes a
sium chloride (KCl) bridge. The measurement half 61.5 mV change in the electrical potential.12

9781449601942_CH06_PASS02.indd 154 01/10/14 6:44 PM


Calculated Values 155

Functional Requirements and diffuses from the sample solution and then through the
Characteristics of the pH System membrane, where it is reduced.15 Electrons are drawn
from the anode surface to the cathode to reduce the
It is postulated that sodium ions in the hydrated glass
oxygen. The current is proportional to the pO2 of the
drift out and are replaced by the smaller hydrogen ions
test solution.
that are present in the sample. This results in a net
The sensitivity of the pO2electrode is related to the
increase in the external membrane potential, which
thickness of the membrane and the size of the cathode
travels through the thin, dry membrane to the inner
area. A micro-ampmeter measures movement of elec-
hydrated glass surface. Chloride ions in the buffer
trons between the anode and cathode, which forms
solution migrate to the internal glass layer, creating a
the electrical current. There are four electrons drawn
potential difference at the pH electrode that, in turn,
for each mole of O2 that is reduced. The reaction at the
signals the external reference electrode. The difference
cathode is summarized as follows:
in voltage is converted and displayed as the pH.
O2 + 4e− 2 O−
pCO2 Electrode System
Functional Requirements and 2 O– + 2 H2O 4 OH−
Characteristics of the pCO2 Electrode Next, elemental silver present at the anode is oxidized
The pCO2 electrode is a modified pH electrode that was and then ionized, forming four electrons before com-
first described by Stowe and later by Severinghaus;13 bining with chloride to form silver chloride. The reac-
today it is known as a Stowe-Severinghaus electrode. tion at the anode is summarized as follows:
The electrode has an outer semipermeable membrane
consisting of Teflon or silicon elastic (Silastic). CO2 4 Ag 4 Ag+ + 4 e−
diffuses into an electrolyte layer; a bicarbonate buffer
covers the electrode glass. When CO2 reacts with the 4 Ag+ + Cl− 4 AgCl
buffer, carbonic acid forms, which then dissociates into Other gases may pass through the membrane, but the
a bicarbonate ion [HCO3–] and hydrogen ions [H+].14 degree of the polarizing voltage does not permit them
CO2 + H2O H2CO3 H+ + HCO3− to be reduced at the cathode. The membrane prevents
proteins and other oxidizing agents from reaching the
The hydrogen ions diffuse across the glass electrode cathode surface. Protein build-up on the membrane is
and the change in [H+] activity is measured using the an important source of measurement error; proteins
same principle as for the pH electrode. The pCO2 is may alter the diffusion of the gases and hinder the
determined from the pH value using the Henderson- electrode response. The sensitivity of the electrode is
Hasselbalch equation: related to the thickness of the membrane and the size
of the cathode area.
pH = pk + log [HCO3–]/pCO2

pO2 Electrode System Calculated Values


Functional Requirements and Hemoglobin/Oxygen Saturation
Characteristics of the pO2 Electrode Oxygen saturation of hemoglobin is the percentage of
The partial pressure of oxygen (pO2) is measured oxygenated hemoglobin divided by total hemoglobin
using the Clark electrode, which is a complete present capable of binding with oxygen. Oxygen satu-
electrical cell. The Clark electrode consists of a ration (sO2) is calculated using the following equation:
small platinum cathode and a silver-silver chloride sO2% = cO2Hb/(cO2Hb + cHHb) × 100
(Ag-AgCl2) anode immersed in a phosphate buffer
that contains additional potassium chloride. The where cO2Hb is the concentration of oxyhemoglo-
platinum electrode is covered with a small layer of bin and cHHb is the concentration of reduced or
electrolyte and a thin gas-permeable membrane made deoxyhemoglobin; the sum of oxy- and deoxyhemo-
of a material such as polypropylene. The membrane globin represents the total functional hemoglobin.
separates the test specimen from the electrode and is Oxygen saturation is a derived value for most blood
selectively permeable to oxygen, which diffuses into gas analyzers. It is only measured by analyzers that
the electrolyte to contact the cathode. The cathode have hemoximetry capabilities. A hemoximeter
potential is adjusted to a constant voltage potential of directly measures the amount of hemoglobin pres-
–0.65 volts (V). When there is no oxygen present in the ent and capable of binding with oxygen.16 Therefore,
solution, the cathode is polarized and the current is the microprocessors of analyzers that calculate
approximately equal to 0 volts. When oxygen is present sO2 assume normal O2 affinity of the hemoglobin.
in the test specimen, a current is produced and oxygen It is important for the clinician to recognize this

9781449601942_CH06_PASS02.indd 155 01/10/14 6:44 PM


156 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

calculation may be approximate and should be inter- spectrophotometer of the analyzer. The hemoglobin
preted with caution. molecule that is bound to oxygen is known as oxyhe-
Oxygen saturation may also be calculated using the moglobin, whereas deoxyhemoglobin or reduced refers
following formula: to a hemoglobin molecule that does not contain oxygen.
Carboxyhemoglobin contains bound carbon monoxide
sO2% = cO2Hb/ctHb × 100% instead of oxygen, and methemoglobin is a hemoglo-
where ctHB includes the carboxyhemoglobin, methe- bin fraction that contains iron in the ferric (Fe3+) form.
moglobin, and sulfhemoglobin fractions. Using this These fractions are summarized in Table 6-4.
equation, the sO2% will never reach 100% if any of these Blood gas analyzers measure total hemoglobin spec-
nonfunctional hemoglobin fractions are present. This trophotometrically.17 Once in the analyzer, the hemo-
calculation should not be used because the dishemoglo- lyzer unit hemolyzes or ruptures the red blood cells in
bins, mentioned above, are present in the blood and the an aliquot of the specimen. A portion of the hemolyzed
findings may be misleading. For example, if a patient sample is transferred to a measuring chamber, also
had 10% carboxyhemoglobin, the sO2 could not be any known as a cuvette. A tungsten halogen lamp or other
higher than 90%, even in fully saturated blood, which light source provides polychromatic light, which is
might indicate an increase in oxygen shunting to the directed toward the sample in the cuvette. Depending
lungs, which would not be accurate.10 on the concentration of hemoglobin in the sample,
light is transmitted through the hemolyzed sample and
toward the spectrophotometer. The specific wavelengths
Total Hemoglobin Measurement: that transmit the color of each hemoglobin fraction are
Oxyhemoglobin and Dishemoglobinemias selected through a monochromater. Transmitted light
Total hemoglobin (ctHb or tHb) must be measured contacts photodetectors that produce a voltage that
because the value is needed to calculate several other corresponds to the amount of light transmitted and
blood gas values. Total hemoglobin is a measure photons of light produced. The microprocessor converts
of all of the hemoglobin fractions detected by the the voltage through calculations into the hemoglobin

TABLE 6-4
Hemoglobin Fractions

Hemoglobin Fraction Abbreviation Description Comments

Total hemoglobin ctHb or tHb Concentration of total hemoglobin


or all fractions measured by
spectrophotometer

Oxyhemoglobin O2Hb or FO2Hb Concentration of hemoglobin that is Normal adult hemoglobin includes 1.5–3.5%
or fraction of oxygenated HbA2, less than 2% HbF, and ~95% HbA,
oxyhemoglobin which is the major adult hemoglobin

Deoxyhemoglobin HHb or FHHb Concentration of hemoglobin that is


or fraction of deoxygenated and is not bound to
deoxyhemoglobin oxygen

Carboxyhemoglobin COHb or FCOHb Concentration of hemoglobin that is Hb affinity for CO is 200 times higher
or fraction of combined with carbon monoxide than for O2; increased in city dwellers and
carboxyhemoglobin smokers; extreme elevation and anoxia in
carbon monoxide poisoning

Methemoglobin MetHb or FMetHb Concentration of hemoglobin that MetHb cannot bind oxygen; normally less
or fraction of contains iron in its ferric (Fe3+) state than 1.5% of total Hb; increased in cyanosis
methemoglobin and hypoxia; causes include exposure to
nitrates and/or benzocaine products

Fetal hemoglobin HbF or FHbF Concentration of hemoglobin F or fetal Makes up 50–80% of total hemoglobin at birth
or fraction of fetal hemoglobin; HbF can bind oxygen very and less than 2% in adults; the concentration of
hemoglobin tightly HbF is increased in some hemoglobinopathies
and in some cases of hypoplastic anemia,
pernicious anemia, and leukemia

Sulfhemoglobin SulfHb or FSulfHb Sulfur molecule attaches to hemoglobin Normally less than 2.0%; cyanosis when
or fraction of and oxygen cannot be transported; increased; occupational exposure to sulfur
sulfhemoglobin may combine with CO to form compounds and pollutants
carboxysulfhemoglobin

9781449601942_CH06_PASS02.indd 156 01/10/14 6:44 PM


Biosensors and Methods Used in the Measurement of Analytes 157

concentrations or fractions. Most blood gas analyzers the Van Slyke equation.19 The base excess is useful in
detect oxyhemoglobin, as well as deoxyhemoglobin, car- evaluating the patient’s acid–base balance in metabolic
boxyhemoglobin, and methemoglobin fractions. disorders. A positive base excess occurs when there is a
The hemoglobin unit must be calibrated using a surplus of HCO3– and a negative base excess when there
known total hemoglobin standard. A calibration curve is a deficit of HCO3–. The calculation of base excess
is electronically developed based on the voltage pro- requires the hemoglobin value, pCO2, and HCO3–; the
duced and is sent to the microprocessor. Sample results base excess at pH of 7.40, pCO2 of 40 mm Hg, and Hb of
cannot be reported if the analyzer fails to calibrate 15 g/dL at a temperature of 37°C is zero.
successfully. Also, quality control using two different
levels of a hemoglobin control must be performed with Base excess = (1.0 – 0.0143 Hb)(HCO3–) –
acceptable results before reporting patient values.18 (9.5 + 1.63 Hb)(7.4 pH) – 24

Today, this value is automatically calculated by the


Hematocrit Measurement microprocessor in the blood gas analyzer.20 The reference
The hematocrit formerly was known as the packed range for base excess in adults is from – 2 to + 3.
cell volume (PCV). When a whole blood specimen is
centrifuged, the red blood cells sediment to the bottom,
the white blood cells and platelets form a middle layer, Biosensors and Methods Used in
and plasma forms the upper layer. The percentage of
red blood cells in the whole blood specimen is known
the Measurement of Analytes
as the hematocrit. Whole blood can be analyzed for many analytes,
including the electrolytes potassium (K+), sodium
(Na+), and calcium (Ca 2+) and metabolites such as
Bicarbonate Content glucose, lactate, blood urea nitrogen (BUN), and cre-
Bicarbonate constitutes a large fraction of the ions atinine. The sensors used for these measurements are
in plasma. Bicarbonate includes true bicarbonate, ion-specific or ion-selective electrodes (ISE).These
carbonate, and CO2 bound in plasma carbamino sensors are membrane-based electrochemical trans-
compounds. True bicarbonates are the largest ducers that respond to a specific ion. Biosensors are
contributor to bicarbonate content. used in analyzers in the traditional clinical labora-
tory, but also in point-of-care (POC) testing devices.
Oxygen Content Biosensors use biologically sensitive material that
contacts the appropriate transducer responsible for
Oxygen content can be measured directly or calculated converting the biochemical signal into an electrical
by the oxygen content equation. signal (Figure 6-1).
ctO2 = (Hb × 1.36 × sO2) (0.003 × pO2) Electrolytes are determined by potentiometric
measurements, a form of electrochemical analysis.21
where In potentiometry, the potential or voltage is measured
between two electrodes in a solution. These potentials
ctO2 is the oxygen content
can also be produced when a metal and ions of that
Hb is the hemoglobin in g/dL
metal are present in a solution. By using a membrane
sO2 is the oxygen saturation in %
that is semipermeable to the ion, different concentra-
pO2 is the partial pressure of oxygen in mm Hg
tions of the ion can be separated. These systems use a
However, the tO2 can be determined with results reference and a measuring electrode. A constant volt-
obtained from an arterial blood sample using the age is applied to the reference electrode; the difference
CO-oximetry test panel, which includes fractional con- in voltage between the reference and measuring elec-
centration of oxyhemoglobin, reduced hemoglobin, car- trode is used to calculate the concentration of the ion
boxyhemoglobin, and methemoglobin. The sum total in solution.
of these hemoglobin derivatives yields the total hemo- Ion-selective electrodes are based on a modifica-
globin concentration. Many current blood gas analyz- tion of the principal of potentiometry.21 The potential
ers either measure or calculate all variables needed to difference or electron flow is created by selectively
calculate the ctO2. transferring the ion to be measured from the sample
solution to the membrane phase. The ISE measures
the free ion concentration of the desired analyte on a
Base Excess selectively produced membrane. Membranes have a
Base excess can be defined as the concentration of complex composition and contain organic solvents,
titratable base when a fluid is titrated to a pH of 7.40 inert polymers, plasticizers, and ionophors. Ionophors
at a pCO2 of 40 mm Hg. However, in practical terms, are molecules that increase the membrane’s permeabil-
the base excess is calculated using a nomogram or with ity to the specific ion.

9781449601942_CH06_PASS02.indd 157 01/10/14 6:44 PM


158 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

Calibrator 1 solution Waste rinse

Injection
port
Cleaning/flush solution
Gas

Valve
Calibrator 1 solution
Sample
Sample
Valve
Valve
Salt bridge
Pump

Reference electrodes

pH pCO2 pO2 K Na Hb

FIGURE 6-1  Schematic of a typical analyzer used to measure blood gas and electrolytes.

Because ISEs produce a direct measurement, there There are also enzyme-based biosensors with poten-
is no need for reagents or the production of a standard tiometric and conductimetric detection methods.23
curve. Results are precise, accurate, sensitive, and specific Conductimetric methods utilize chemical reactions
for the analyte that is being tested. Ion-selective electrodes that produce or consume ionic substances and alter the
are also cost effective, have a rapid analysis time, and are electrical conductivity of a solution. In this technology,
easily maintained and adapted toward automation. polymembrane ion-selective electrodes are used. Blood
The corresponding membrane component is unique urea nitrogen (BUN), glucose, and creatinine may be
for a specific ISE membrane. For example, the sodium measured using this technology. The BUN biosensor
ISE membrane contains silicate in glass; the potassium immobilizes the enzyme urease at the surface of an
ISE membrane contains valinomycin; the chloride ISE ammonium ISE; the urease catalyzes the breakdown
membrane contains solvent polymeric membranes. of urea to ammonia (NH3) and CO2. Subsequently the
ISEs are also available for chloride (Cl–), calcium (Ca2+), ammonia forms ammonium, which is detected by the
magnesium (Mg2+), and lithium (Li+). ISE. The signal produced by the ISE is related to the
Amperometric methods measure the current flow concentration of blood urea nitrogen in the sample.
produced from oxidation-reduction reactions. Types of Biosensor systems can also use optical detection
amperometry include enzyme electrodes, such as the to measure glucose, bilirubin, and other analytes. The
glucose oxidase method and the Clark pO2 electrode, sensors include immobilized enzymes and indicator
previously discussed. These types of designs are known dyes and may be detected using spectrophotometer,
as biosensors and are adaptable for testing in the clini- fluorescence, reflectance, or luminescence.24
cal laboratory as well as for point-of-care (POC) testing.
Enzyme-based biosensor technology was first devel-
oped to measure blood glucose. A solution of glucose Phases of Analysis
oxidase is placed between the gas-permeable mem- Within the test setting, control of variables that may
brane of the pO2 electrode and an outer membrane affect the three phases of analysis must be evaluated.
that is semipermeable.22 Glucose in the blood diffuses Preanalytical test variables that may alter patient results
through the semipermeable membrane and reacts with include correct patient identification, turnaround time,
the glucose oxidase. Glucose is converted by glucose transcription errors, patient preparation, specimen
oxidase to hydrogen peroxide and gluconic acid. A collection, and specimen transport. There are many
polarizing voltage is applied to the electrode, which oxi- individuals involved in the preanalytical testing phase;
dizes the hydrogen peroxide and contributes to the loss therefore, a coordinated effort among the healthcare
of electrons. Oxygen is consumed near the surface of providers involved in the process is essential. Following
the pO2 electrode and its rate of consumption is mea- specimen collection and transport, the sample must be
sured. The loss of electrons and rate of decrease in pO2 correctly processed or maintained prior to analysis.
is directly proportional to the glucose concentration in The analytical stage includes the actual testing of
the sample. Enzyme-based biosensors are also used to the specimen. A specific testing protocol with stan-
measure cholesterol, creatinine, and pyruvate. dard operating procedures (SOPs) for each analyzer is

9781449601942_CH06_PASS02.indd 158 01/10/14 6:44 PM


Phases of Analysis 159

needed. This includes criteria to accept or reject speci- Preanalysis Phase: Specimen Handling and
mens. All specimens must be analyzed consistently Special Considerations
by the testing personnel, who must follow the specific
Arterial blood collection begins by confirming the
procedure directions outlined in the procedure manual.
identification and location of the patient. The test order,
The process that occurs during sample analysis is
or requisition, and patient identification must agree.
provided in Figure 6-2. Quality control (QC) is a very
Any identification discrepancies must be resolved and
significant component to assess the quality of the ana-
corrected before proceeding to collect the specimen.
lytical testing phase. Quality control is used to monitor
Correct specimen collection and transport are essen-
and assess the accuracy of specimen analysis. QC uses
tial to ensure accurate results for the patient. Failure
samples with known values of each analyte with a range
to properly collect or transport the sample can lead to
of acceptable values given. In the postanalytical phase,
erroneous results that may affect the diagnosis, treat-
the results are evaluated for error and proximity to nor-
ment regimen, and clinical outcome.25 Arterial blood
mal limits.
gas specimens are most often collected using a single
Of course, technical competence is a requirement
percutaneous needle puncture from the radial artery,
for all testing phases. Proper training of personnel who
although specimens may also be collected from bra-
perform the analysis is essential and should include
chial, femoral, or pedis arteries. The temporal artery
education standards, learning objectives, an evaluation
may also be used for collection in newborns. Capillary
of technical competence, in-services, and continuing
blood gas collections from the heel or earlobe of infants
education. Work quality must be evaluated and correc-
are also acceptable for analysis; however, reference
tive actions suggested if needed.

Pre-analytical phase Analytical phase


• Values for Verify order Assess sample and
non-invasive use SOP to determine
monitoring if sample can be 1
(i.e., Sp02, analyzed
HR, total RR, Contact personnel
PET CO2, responsible for ABG
TCPCO2) analysis to ensure
• Ventilator equipment is functioning Assess sample and
settings Sample Yes use SOP to determine
• Temperature meets if sample can be
• Activity criteria analyzed
Assess patient and
document findings
No

• Remove air Contact clinical


Obtain minimum Assess analyzer
• Remove clots team and request
required sample function
• Mix sample redraw

Label syringe
Troubleshoot No In
• Patient name calibration
• Ventilator and analyzer
or oxygen Transport
settings (if Post-
specimen to the
applicable) analytical Yes
ABG lab
phase
Analyze sample
Yes Analysis
1 errors
Review results for
No critical values or
errors

Yes Critical
values

No
Report results
using critical value Report results
procedure

FIGURE 6-2  Process flow for the three phases of blood gas and analyte measurement.

9781449601942_CH06_PASS02.indd 159 01/10/14 6:44 PM


160 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

ranges and results differ from arterial samples. Venous collection when held at room temperature. Specimens
specimens are commonly used for venous pH, pCO2, that cannot be analyzed immediately must be placed
and bicarbonate testing. Attempts should be made to within an ice slurry and maintained at a temperature
keep sample sizes as small as is technically feasible to of 32–39.2°F (0–4°C) for no longer than 30 minutes.
limit blood loss, particularly in neonates.2 Once col- Specimens should not be held in ice alone because
lected, the specimen must be accurately labeled with the sample may freeze and red cells may hemolyze.
the patient’s name, identification number, location, Oxygen may be metabolized by white blood cells after
FIO2, and temperature as well as the collector's initials, specimen collection, especially if the patient has an
date, and time of collection.2 Specimen labeling must elevated white blood cell count. Delays in transport
occur even in cases where the individual collecting the may also increase diffusion of gases through the plastic
specimen also performs the analysis.26 syringe and increase the likelihood of potassium
Following collection of percutaneous samples, all diffusion from the red cells. Preanalytical error may
air bubbles must be immediately removed by gently lead to measurement error and improper medical
tapping the side of the syringe. The syringe should not diagnosis.
be agitated. Significant error may occur when even a Prior to analysis, gently mix the specimen to obtain
small amount of air bubbles is found in the sample.27 a homogeneous sample; this can be accomplished by
When collecting specimens from indwelling arterial gently inverting the sample or by rolling the syringe
catheters, first remove 1–2 mL of blood from adults and in the palms of the hands. Never shake the specimen
0.2–0.5 mL from infants. Flush the cannula with sterile, because this may hemolyze the red cells, releasing
physiologic saline to prevent clotting in the cannula. potassium and altering the results.
Saline and heparin in catheter lines can dilute the sample
and falsely decrease the pCO2 and hemoglobin.28,29
Preanalysis Phase: Calibration Principles
Temperature Correction for Blood Gas Values High and low calibration is required for all measured
Patient temperature affects blood gas values. Blood gas and reported laboratory analytes in order to verify
analyzers assume the patient’s temperature is 98.6°F the analyzer is operating correctly. Today, most blood
(37°C). In cases of hypothermia due to surgery or pro- gas analyzers are self-calibrating, controlled through
longed exposure to cold, where the body temperature the microprocessor and monitored constantly. The
may be significantly lower than 98.6°F (37°C), or hyper- frequency and type of calibration that is programmed
thermia due to fever, the patient’s actual body tempera- into the instrument varies and is based on the manu-
ture may be manually entered into the analyzer so that facturer, accreditation standards, and the facility’s
temperature-corrected pH, pCO2, and pO2 values can operation schedule.
be calculated.30 The algorithms used for these calcula- A one-point calibration uses only one calibration
tions are generally found in the instrument operator’s standard; the electrical output is adjusted to a single
manual. The use of the temperature correction is not standard. A one-point calibration of pO2 and pCO2 is
standardized, and there is a lack of agreement in the lit- generally automatically performed every 30 minutes.
erature regarding its use. Some report corrected values One-point calibrations should be manually performed
provide a more correct indication of the acid–base bal- prior to sample analysis. In a two-point calibration, the
ance and oxygenation state of the patient. For example, response of the electrode is measured against known
pO2 changes approximately 7% for each 1°C deviation values for both a high and low standard. The values
from 37°C. Thus, it is advisable to perform temperature are plotted and a linear calibration curve is derived; all
corrections for measured pO2 even for a 1°C devia- subsequent measurements are compared against the
tion. Both the pO2 value measured under the standard calibration line. Most blood gas analyzers automatically
temperature of 98.6°F (37°C) and the temperature- perform a two-point calibration every 8 hours.
corrected value should be reported.31 It is generally
accepted that it is not necessary to correct the pH and Functional Requirements of Calibration
pCO2 for hyperthermia and they are generally reported The pH system is calibrated against primary calibration
only when requested by the physician.32 A temperature buffers that are phosphate solutions and that must meet
correction does not affect the calculated HCO3–. the standards of the National Institute of Standards
and Technology (NIST). These calibrators are pre-
Key Points for Specimen Collection/ pared from standard reference materials—potassium
Preparation for Analysis dihydrogen phosphate and disodium monohydrogen
Blood gas specimens must not be exposed to room air phosphate—according to a specific protocol to pro-
during collection, transport, or measurement. Room duce two buffer solutions. The first has a pH of 6.841 at
air has a pO2 of approximately 150 mm Hg, which can 98.6°F (37°C) and the second has a pH of 7.383 at 98.6°F
affect the value of oxygen in the sample. Specimens (37°C). The buffers must meet NIST specifications; they
must be transported for analysis within 10 minutes of are commercially available and manufactured to a size

9781449601942_CH06_PASS02.indd 160 01/10/14 6:44 PM


Phases of Analysis 161

and shape to fit into the reservoirs of the analyzer. The barometric pressure value is known to the microproces-
tolerance for calibrators should be ± 0.003 in order to sor, which then calculates the pO2 and pCO2 based on
achieve standard deviations of ± 0.005 to ± 0.01. Dalton’s law. Other models require that the operator
The calibration of the gas system requires known manually enter the barometric pressure.
concentrations of O2 and CO2 gases to be introduced into
the measurement chamber. Pure O2, CO2, and N2 can Analysis Phase: Laboratory
be purchased as compressed gases with a certificate of Blood Gas Analyzers
analysis provided by the manufacturer and then mixed
into the required composition, or they can be purchased Principles of Operation
commercially in the appropriate calibration mixture. The The basic principles of operation for laboratory blood
low gas mixture calibrator and high gas mixture calibra- gas analyzers are the previously described electrodes
tor compositions are shown in Table 6-5. Calibration for pH, pCO2, and pO2; spectrophotometric analysis of
using these mixtures will provide a calibration range of hemoglobin; and ion-specific electrodes for the measure-
0–152 mm Hg for O2 and 38–80 mm Hg for CO2. The ment of electrolytes. The principle of operation is shown
pO2 electrode can be calibrated using “no atmosphere” in Figure 6-3. Approximately 50–120 µL of a well-mixed
air as the low calibrator and “room air” as the other cali- arterial blood sample are injected through the inlet and
brator. Today, gas calibrators are included in the testing sample probe into the measuring chamber. The specimen
cartridges for most blood gas analyzers. contacts the surface of each electrode for several seconds.
During calibration of the gas system, gas released
from the tanks is pumped into the calibration buffers. Calibration
The solutions are mixed, warmed to 98.6°F (37°C), and Calibrator gases and buffers enter through the valve
a small aliquot moved to make contact with the surface to the chamber area maintained in a fluid and metal
of the pO2 and pCO2 electrodes. A voltage measurement bath at a constant temperature of 98.6°F (37°C) ± 0.1°C.
is taken, which is corrected for the barometric pressure; The measuring and reference electrodes are located
the microprocessor analyzes the values and derives a in this chamber. The high pH and low pH calibrators
calibration curve for pH, pO2, and pCO2. Some analyz- enter in alternating mode into the chamber, generating
ers have an internal barometer or transducer so that the electrical responses for the upper and lower pH limits

TABLE 6-5
Gas Calibration Mixtures

pO2 (%) O2 (mm Hg) pCO2 (%) CO2 (mm Hg) N2 (%)

Low gas mixture 0 0 5 59 95

High gas mixture 20 150 mm Hg 10 80 mm Hg 70

Sample probe valve


Admits calibrator gases, buffers Pump devices draw calibrators,
and sample into chamber buffers and sample into chamber

Measuring chamber

High and low pH High and low gas


calibrators are mixtures for CO2 Sample contacts
Fluid or metal bath Measuring and and O2 alternatively
alternatively electrodes and Sample
maintains chamber reference electrode admitted into Sample
admitted into remains in chamber pumped
at temperature of protrude chamber. Upper and measured
chamber. Linear to reach temperature to waste
37±0.1°C into chamber lower limits for CO2
calibration curve equilibrium
formed and O2 are set

Output
Gas calibration phase Digital output displayed, printed, or
Linear pH calibration sets upper and lower limits reported through computer
curve established for CO2 and O2 information system for sample

FIGURE 6-3  Process that occurs during the analysis of whole blood for gas and analyte measurement.

9781449601942_CH06_PASS02.indd 161 01/10/14 6:44 PM


162 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

and producing a linear pH curve. The high and low gas lead to measurement error if the sample does not reach
calibrators for pO2 alternatively enter the chamber, the 98.6°F (37°C) ± 0.1°C. The analysis process is outlined in
electrical responses are measured, and a standardized Figure 6-3. Temperature control errors may result from
linear curve is generated. The same process also occurs pinched or clogged tubing within the analyzer or from
for pCO2 with the high and low calibrator gases enter- clogs or spaces in the sample stream. Point-of-care testing
ing the measuring chamber, generating voltages, and devices may be more vulnerable to analytical errors and
producing a linear calibration curve. After an acceptable have a higher rate of error when compared to analyzers in
calibration, the blood sample is introduced and analyzed. a core or satellite laboratory.33 Sources of error associated
The electrodes have a threaded neck with a leak-proof fit with blood gas analysis are summarized in Table 6-6.
and the sample contacts the tip of each electrode. The pH
electrode has glass that is sensitive to [H+] ions. Postanalysis Phase: Quality Control and
An electrical output is generated for each parameter
of the sample and then sent to the microprocessor;
Reporting Principles
the results are sent to the computer screen or printer. Assessment of Analyzer Performance
A report is generated, which can be sent through the Total quality management (TQM) is a management
laboratory information system to the patient’s location process designed to improve quality of care, maintain
or healthcare provider. Patient demographics, sample patient safety, and control the cost of care. In terms of
type, FIO2, and temperature are entered by the operator laboratory analysis, TQM includes quality assurance
prior to sample analysis. (QA) and quality control (QC). Quality assurance deals
with the wider measures of laboratory performance,
Analysis Phase: Sources of such as turnaround time, specimen and patient identi-
Measurement Error fication, and appropriate test utilization. Through QA
Most errors in blood gas analysis occur in the preana- processes, problems are identified and solutions pro-
lytical phase, including specimen collection and han- vided to mitigate the problem.
dling. Insufficient sample and/or inadequate mixing Analyzers must be maintained to ensure proper
of the blood specimen prior to analysis may lead to a performance; careful maintenance of the analyzer and
nonhomogeneous distribution of red blood cells across specimen quality are important in providing accurate
the electrode junction. Analytical errors such as prob- and timely results. The microprocessor of the analyzer
lems with maintaining the temperature control can displays the diagnostic maintenance routine required

TABLE 6-6
Sources of Error Associated with Blood Gas Analysis

Preanalytical Errors Analytical Errors Postanalytical Errors

Wrong patient drawn Insufficient sample Reporting incorrect result to clinician

Poor drawing technique Calibration set points not accurate Transcription errors

Failure to follow protocol for specimen Quality control not run or out of control Failure to recognize and interpret flags and
collection instrument errors

Failure to mix heparin sufficiently with sample Maintenance not performed

Air introduced into syringe Failure to run calibration

Specimen exposed to air Temperature control errors

Delay in transportation for testing

Sample not kept cold during transport

Failure to mix sample adequately before


analysis

All air bubbles are not removed from the


sample

Presence of fibrin clots in the sample

Analysis of a clotted specimen

9781449601942_CH06_PASS02.indd 162 01/10/14 6:44 PM


Phases of Analysis 163

by the manufacturer and also displays warnings or State and federal accreditation agencies require that
indicators of problems that must be addressed and cor- three levels (low, normal, and elevated) of each analyte
rected. Regular maintenance in accordance with the must be tested in each 24-hour period. Most facilities
manufacturer’s recommendations is required for all analyze all three levels in each 8-hour shift.
blood gas analyzers; the schedule should be adjusted Postanalytical variables, the third stage of analysis,
to the needs of the particular facility. This includes include the accurate recording and reporting of results.
routine maintenance, which is performed on a daily, Results must be correctly reported to the appropriate
weekly, or monthly basis. healthcare provider in a timely manner. Patient results
Corrective maintenance is required if there are prob- not within the reference range, and in particular critical
lems with quality control or performance concerns with values, must be reported to and documented with the
the analyzer. The instrument manual provides specific healthcare provider.
guidelines for routine, preventative, and corrective main-
tenance requirements for each analyzer. In general, fre- Reporting Values
quency of maintenance is directly related to the number Reference ranges for some common parameters are
of blood gas analyses performed on the instrument. summarized in Table 6-7. Results must be reported
It is important to maintain a clean sample chamber through the information system, electronic medical
and path. Although automatic flushing to clean the
record, or instrument interface in a timely manner.
sample chamber and pathway is an element of most
blood gas analyzers, it may still be necessary to manu-
ally clean these areas with implements or solutions Importance of/Rationale for Critical Values
recommended by the manufacturer. Fibrin strands or for Blood Gases and Analytes
small clots may be present in samples or may develop in Critical values, also known as panic values, are those
the sample as it is warmed in the temperature chamber. testing results that present a life-threatening situa-
Fibrin and clots will alter calibrations and measure- tion for the patient. 34 Timely and accurate reporting
ments by affecting the contact of blood, gases, or buf- of critical values to licensed medical professionals
fers with electrode membranes. is required by laboratory accrediting bodies and is
Quality control is a required component of labora- recognized as an important patient safety initiative. 35
tory analysis. It is not only necessary to ensure that the Critical limits may vary with the laboratory and the
analyzer is operating correctly and producing accurate medical facility. Table 6-8 shows the upper and lower
results, but also required for accreditation by agencies, limits for pertinent clinical chemistry laboratory
including the College of American Pathologists, and to tests. 36
comply with the Clinical Laboratory Improvement Act
of 1988.1
Proficiency testing is an external quality assess- Assessment of Analyzer Performance:
ment process in which simulated patient specimens Quality Control
are produced from a common pool and analyzed by It is essential to only report patient results that are
participating laboratories. The purpose is to evaluate accurate and precise so that the healthcare provider
each laboratory’s performance on specific analytes. can make a reliable diagnosis and treatment regimen.
Target values are established for each tested param- Error refers to deviations from the true value. Testing
eter as well as for the method of analysis. Typically, errors are categorized as either random/wild or sys-
proficiency testing occurs in three cycles per year; tematic. All test systems attempt to identify and mini-
there are five specimens required for each specific mize measurement errors. Systematic error occurs in
analyte. For laboratories to be graded “successful” in some predictable manner. The measurement value is
most clinical laboratory areas, including chemistry, either overestimated or underestimated, but not both.
correct results must be produced for that analyte on It is controlled through proper calibration and qual-
four out of the five specimens. A minimal score of ity control of the testing system. Systematic error is
80% must be achieved in three consecutive cycles. explainable and has a correctable cause. Systematic
All unacceptable performances must be assessed error may be caused by an inaccurate calibrator or
and an explanation provided for the measurement standard, improper handling of samples or reagents, or
error. Of course, the problem causing the error must instrument malfunction. It can generally be identified
be identified and corrected. As a component of the and corrected through quality control by identifying
laboratory accreditation process, proficiency testing is shifts, trends, and violations of the Westgard Rules (see
mandatory.1 more on these rules later in this section).37 By contrast,
Quality control materials should be analyzed after a random error is unpredictable and results from uncon-
successful calibration, following completion of routine trollable factors. It is introduced by chance and can be
maintenance procedures, and after completing any cor- minimized, but never eliminated. Random errors may
rective maintenance or troubleshooting of the analyzer. appear on both the high and low sides of the true value.

9781449601942_CH06_PASS02.indd 163 01/10/14 6:44 PM


164 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

TABLE 6-7
Reference Values

Test Specimen Type Reference Range

Blood Gases

pH Arterial 7.35–7.45

pH (newborn) Arterial 7.25–7.45

pCO2 Arterial 35–45 mm Hg

pCO2 (newborn) Arterial 27–40 mm Hg

pO2* Arterial 83–108 mm Hg

pO2 (newborn) Arterial 55–90 mm Hg

HCO3 Arterial 21–28 mmol/L

HCO3 (newborn) Arterial 17–24 mmol/L

T CO2 Venous 22–29 mmol/L

T CO2 (newborn) Venous 13–22 mmol/L

sO2 Arterial 95–98%

sO2 (newborn) Arterial 40–90%

Base excess Arterial –2 to +3

Base excess (infant) Arterial –10 to –2

Chemistry

Glucose (adult: fasting) Whole blood, serum, or plasma 60–95 mg/dL

Glucose (infant and child) Whole blood, serum, or plasma 70–100 mg/dL

Glucose (newborn) Whole blood, serum, or plasma 50–80 mg/dL

Potassium Whole blood, serum, or plasma 3.5–5.1 mmol/L

Potassium (newborn) Whole blood, serum, or plasma 3.0–5.8 mmol/L

Sodium Whole blood, serum, or plasma 136–145 mmol/L

Sodium (infant) Whole blood, serum, or plasma 139–146 mmol/L

Chloride Whole blood, serum, or plasma 98–107 mmol/L

Chloride (newborn) Whole blood, serum, or plasma 98–113 mmol/L

Hematology

Hemoglobin (male) Whole blood 13.5–17.5 g/dL

Hemoglobin (female) Whole blood 12.0–16.0 g/dL

Hemoglobin (newborn) Whole blood 10.0–17.0 g/dL

Hematocrit (male) Whole blood 37–48%

Hematocrit (female) Whole blood 35–45%

* pO2 decreases with age and high altitude.

9781449601942_CH06_PASS02.indd 164 01/10/14 6:44 PM


Phases of Analysis 165

TABLE 6-8
Critical Values for Some Common Laboratory Analytes

Test Specimen Type Lower Limit Upper Limit

Blood Gases

pH Arterial and capillary 7.20 7.60

pCO2 Arterial and capillary 20 mm Hg 70 mm Hg

pO2 Arterial 40 mm Hg

HCO3 Arterial and capillary 10 mmol/L 40 mmol/L

Chemistry

Glucose (adult) Whole blood, serum, or plasma 40 mg/dL 450 mg/dL

Glucose (infant < 1 year) Whole blood, serum, or plasma 40 mg/dL 400 mg/dL

Glucose (newborn) Whole blood, serum, or plasma 30 mg/dL 200 mg/dL

Potassium Whole blood, serum, or plasma 2.8 mmol/L 6.2 mmol/L

Potassium (newborn) Whole blood, serum, or plasma 2.8 mmol/L 6.5 mmol/L

Sodium Whole blood, serum, or plasma 120 mmol/L 160 mmol/L

Sodium (infant) Whole blood, serum, or plasma 125 mmol/L 150 mmol/L

Hematology

Hemoglobin (adult) Whole blood 6 g/dL 20 g/dL

Hemoglobin (newborn) Whole blood 10 g/dL 20 g/dL

Their effect can be reduced by producing repeated frequency of each result against the concentration
measures of the same quality. Random error exhibits or amount of the analyte should produce a normal,
a Gaussian or normal data distribution, which enables Gaussian distribution. Based on the analysis of the QC
us to make probability statements about measurement material, parameters are established for results that
accuracy. An outlier is a value that is found outside of are plus or minus 1 standard deviation (± 1 SD), plus
the normally distributed data. or minus 2 standard deviations (± 2 SD), and plus or
Quality control (QC) should be performed at least minus 3 standard deviations (± 3 SD) from the mean.
once per shift. Electronic QC, which is a feature of Laboratory limits are generally set to ± 2 SD, which
many analyzers, uses an analyzer signal that mimics means that based on the Gaussian distribution, 95.0%
a sample. It is economical, easy to run, and reliable; of the QC results will be within 2 SDs of the mean.
however, it does not evaluate the operator or all sys- Thus, 5% or 1 out of 20 QC results will fall outside of
tems within the analyzer. Thus, it is essential when the limits as a result of random error.
appropriate to also analyze commercially available QC Levey-Jennings plots are used to track QC perfor-
materials. The frequency of QC analysis depends on mance over a period of time. This process assists in
the instrument, its stability, and the manufacturer’s identification of shifts and trends that alert the opera-
specification, as well as government regulations and tor to possible problems in the testing system. A shift
the policy of the healthcare system. Daily instrument shows that the results are biased and “shifted” in one
setup involves calibration and running QC. Normal direction. The values are all shifting either above or
and abnormal QC with known results are analyzed and below the mean. Shifts are sudden and show an abrupt
compared to known ranges. The result rarely perfectly change in consecutive results. Shifts are most often
matches the mean value every time. Limits of variation attributable to instrument malfunction or errors in
are established. If QC results are within the limits, we operator technique. A Levey-Jennings plot showing a
can assume that patient results are also acceptable and shift is provided in Figure 6-4.
reportable. By contrast, a trend is a gradual change in consecu-
Repeated measures of a given analyte on a given tive control results with all results going upward or
instrument will cluster around the mean. Plotting the downward. A trend results from systematic drift due to

9781449601942_CH06_PASS02.indd 165 01/10/14 6:44 PM


166 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

will detect the characteristic when it is not present.


Shift
QC-Calcium mEq/dL Thus, test systems with low specificity will have a high
7.6 percentage of false positive results. Sensitivity is the
7.5 ability to detect small amounts of the characteristic of
7.4 interest; highly sensitive tests will detect small amounts
7.3
of the analyte and will also differentiate between small
Calcium

7.2
7.1 amounts of different amounts of the analyte. Tests with
Mean = 7.0 mEq/L
7.0 poor sensitivity will produce a high percentage of false
6.9
negatives; the phenomenon is not detected when it is
6.8
6.7 indeed present. In a perfect test setting, all methods
0 5 10 15 20 25 would achieve 100% sensitivity and 100% specificity;
Days because the parameters are inversely related, this of
course is not possible. Thus, test systems that are at
least 90% sensitive and 90% specific are recommended.
FIGURE 6-4  Shift. Screening tests generally promote a higher level of sen-
sitivity and a lower level of specificity, so as to not miss
a characteristic or condition. This generally prompts
Trend
QC-Calcium mEq/dL follow-up testing that is more specific, but perhaps less
7.2
sensitive. Calibration that fails or quality control values
7.1 Mean = 7.0 mEq/L that are not within control limits must be investigated
7.0 and corrective action taken. All corrective measures
6.9
6.8 must be documented.
Calcium

6.7 In summary, internal quality control requires that


6.6
6.5 controls are a part of internal QC and it should be run
6.4 as often as specified by the instrument manufacturer.
6.3 It should also be run whenever there is concern about
6.2
0 5 10 15 20 25 results or the quality of the testing system. Of course,
QC should be rerun if previous controls were not in
Days
control. It is important to emphasize that the operator
cannot report patient results if QC results are not
FIGURE 6-5  Trend. within control.
The Westgard Rules are six rules used to examine
deterioration of a reagent or control material. Trends quality control charts to determine possible problems.39
may also be caused by failure of a component within The type of error, random or systematic, can be identi-
the analyzer. An example of a trend is shown in the fied. At least two levels of control must be run. If any
Levey-Jennings plot in Figure 6-5. of the six rules are broken, patient results cannot be
A high level of precision indicates reproducible mea- reported. Once the problem is identified and corrective
surements; precise results are reproducible, reliable, action taken and documented, it may be necessary to
and consistent. They are most affected by random error. reanalyze patient samples from previous testing, espe-
The greater the random error, the less precise is the cially if a systematic error is identified. Laboratories
measurement. Precision is enhanced by the use of stan- may choose to use all or some of the Westgard rules;
dardized measurement methods, which include train- however, they must use at least one for random and one
ing and certification of the operator.38 Poor precision for systematic error detection.
results from poor technique. Precision is also enhanced The 12s rule is a warning rule that describes random
by refining instruments through automation and by error; it states that there is a problem if one QC value
repeating the measure to reproduce the results. falls more than 2 SD above or below the mean. Random
Accuracy is the degree to which the test system error is also associated with violations of the 13s and R4s
measures the analyte of interest. Accuracy refers to rules; violation of either of these rules requires that the
agreement with the true value. It is most affected by run be rejected. The 13s rule violation occurs when one
systematic error; the greater the systematic error, the result falls outside of the 3 SD limit; the R4s rule viola-
less accurate is the result. Accuracy is assessed by tion occurs if the difference between the highest and
comparing the results to the “gold standard” of test- lowest results exceeds a total range of 4 SD. Systematic
ing, or the reference technique considered to be the error is associated with violations of the 22s, 41s, and
most accurate for a laboratory parameter. Accuracy is 10x; in each case the run should be rejected. The 22s
affected by both specificity and sensitivity. Tests with violation occurs when two consecutive controls exceed
high specificity detect and measure only the charac- either the +2 SD or –2 SD limits; the 41s violation occurs
teristic of interest whereas tests with low specificity when four consecutive controls exceed either the +1 SD

9781449601942_CH06_PASS02.indd 166 01/10/14 6:44 PM


Emerging Technology: Point-of-Care Analyzers 167

TABLE 6-9
Westgard Rules

Rule Description Type of Error

12s At least one QC value falls more than 2 SD above or below the mean. Warning. Random

13s Result falls outside of 3 SD limit. Reject Run. Random

22s Two consecutive controls exceed the +2 SD or –2 SD limit. Reject Run. Systematic

R4s Difference between highest and lowest result of a run exceeds 4 SD. Reject Run. Random

41s Four consecutive controls exceed the +1 SD or –1 SD limit. Reject Run. Systematic

10x Ten consecutive controls fall on the same side of the mean. Reject Run. Systematic

or –1 SD limits. When 10 consecutive controls fall on Biological sensors or immunosensors have been
the same side of the mean, the 10x rule is violated. The developed to measure troponin, infectious agents, and
Westgard rules are summarized in Table 6-9. antibodies to identify an immunologic response to
infectious agents. In this type of flow-through technol-
ogy, a gold-labeled antibody is bound to a porous surface
Emerging Technology: Point-of- matrix. If the sample contains the analyte to be tested
for, the analyte binds to the antibody. Next, a second
Care Analyzers antibody is added that is labeled with biotin or another
Point-of-care testing is a rapidly growing part of health- measureable compound, forming a sandwich contain-
care and takes place in critical care units, surgery, the ing the first antibody, the analyte, and then the second
emergency department, cardiac care units, and neo- antibody. This complex is trapped on the membrane, but
natal and pediatric units. Other uses for POC testing can travel laterally along the membrane until it reaches
include interfacility transport and physician office test- the “capture area,” where the compound streptavidin
ing. Benefits of POC include rapid turnaround time and is bound to a solid, nonmovable phase. Biotin in the
enhanced patient management. The goal of POC testing antibody binds to the streptavidin, which immobilizes
is to offer a test whose result provides a more rapid, yet the complex. It is visualized as a colored band, which is
still accurate result to the healthcare provider that leads measured and then quantitated using the reflectometer.
to a more timely medical decision and the initiation of Other technologies adapted to POC testing include
appropriate care. light scattering, used in coagulation testing; spectro-
POC technologies are built on principles similar to photometry for bilirubin, hemoglobin, and chemistry
those of clinical laboratory analyzers. Electrochemistry analytes; electrical impedance for hematology blood
has been developed for the POC analysis of glucose, cell counts, and fluorescence for C-reactive protein
pH, blood gases, electrolytes, BUN, and creatinine. (CRP), cardiac markers, and drugs.
Lateral flow-immunoassay is used to identify infectious POC blood gas analyzers permit in vitro analysis
agents such as group A streptococcus (Streptococcus at the patient’s bedside, in the emergency room, or
pyogenes), viruses such as influenza, human chorionic in the intensive care unit. These units use solid state
gonadotropin (hCG) for pregnancy, and certain cardiac sensors with fluorescence or thin-film electrodes.
markers. These methods were first developed for qualita- The microchips, reagents, calibrators, and a sampling
tive testing, or to identify the presence of an analyte or device are all contained within a disposable cartridge
compound, but now have quantitative capabilities when system for single analysis. Healthcare facilities can
combined with a detection system. The test system con- select cartridges with additional test options, including
sists of layers of a porous material that contains reagents potassium, glucose, BUN, and lactate. These are usu-
specific to react with the analyte to be tested. The top ally battery operated, but some also offer the advantage
layer contains a semipermeable membrane that will of operating using an electrical output. Manufacturers
trap red blood cells and other larger molecules that may provide a range of flexibility as to the number of tests
interfere with the test. As the sample diffuses through per cartridge (single or multiple) and test menu based
the membrane, if present, the analyte will react with the on the needs of the facility.
reagents and form a chromogen, or colored compound. The standard components of most POC units include
The color intensity is proportional to the amount of an operator interface, a bar code device to easily iden-
analyte present. This can be quantitated using principles tify the type of test being performed, a sample delivery
of light scattering, reflectometry, electrochemistry, or method, a reaction cell, sensors, quality control, data
turbimetric methods. management, storage, and a retrieval system.

9781449601942_CH06_PASS02.indd 167 01/10/14 6:44 PM


168 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

Advantages of POC devices include their ease of use facility and to the patient. Duplicate testing systems
and rapid results—most results can be available in min- for the same analyte add cost to the facility and to the
utes. Because whole blood can be tested, minimal speci- laboratory when considering the cost to purchase or
men processing is needed; the sample does not have rent the analyzer as well as costs for supplies, reagents,
to centrifuged and the plasma separated from the red and maintenance. Finally, POC testing does not always
blood cells prior to testing. There are minimal operating completely correlate with values obtained on tradi-
steps and the units are small and portable. The reagent tional laboratory analyzers, due to specimen type and
cartridges eliminate the need to prepare reagents and methodology. Thus, the healthcare provider must be
there are flexible test menus that can be aligned with cognizant of the type of analysis performed before
the needs of the unit. Calibration and quality control are altering a diagnosis or treatment regimen. Even with
integrated into the unit, which eliminates the need for broader menu flexibility, POC testing does not offer
separate calibrators and QC material. The calibration the comprehensive testing menu of the core clinical
and QC, however, cannot be overridden, so the operator laboratory. Yet POC testing fulfills important and criti-
cannot report a patient result if the calibration fails or if cal healthcare needs of patients and providers, and is
the QC is out of control. indeed here to stay. Future developments in the area of
There are, however, potential concerns with POC POC testing will most likely continue.
testing. With diverse testing personnel from a variety
of education, or lack of education, backgrounds, test-
ing may not be performed correctly. Preanalytical Current Blood Gas Technology
errors involving sample identification, collection, and Prior to 2005, blood gas analyzers directly measured
input are also possible concerns. Those who are not pH, pO2, and pCO2 and provided calculated param-
educated on the importance of sample collection and eters for HCO3–, percent oxygen saturation, and base
testing protocol may perform tests incorrectly and excess. These were large analyzers with gas tanks and
report invalid results. These results may negatively manual quality control. Sampling was more cumber-
impact patient care. Therefore, problems with training some and specimens could be easily exposed to air
and competency of operators remain a large concern. during collection and sample analysis. Today’s analyz-
Quality control and a proficiency testing protocol ers provide a variety of test menus, which may include
with corrective actions and documentation need to electrolytes and other measured analytes and self-
be provided for any instrument malfunctions or out contained reagent cartridge systems. Quality control
of control situations. Although some testing devices is electronically generated and there are features for
provide auto-verification and prevent reporting of auto-calibration and auto-verification. Manufacturers
patient results when calibration or quality control fails, offer a complete testing approach that includes a corre-
other analyzers permit the operator to override and sponding sample collection device, methods of analysis,
report the results. There may be problems with the and reporting of results, which often can be directly
accurate and timely recording of data, including QC, entered into the patient’s electronic medical record.
calibration, and patient results. Because some opera- Rear-venting syringes with lyophilized heparin improve
tors are not trained sufficiently to learn the importance the sample collection by reducing exposure to oxygen
of laboratory testing, significant errors may occur in and minimizing the fibrin clot formation.
each phase of testing. The desire to turn out a result,
any result—accurate or not—may be the overriding
goal because the operator has other responsibilities to
Matching Analyzer Type to
their patient. Some POC devices are not electronically Clinical Setting
interfaced into the patient’s medical record and may Today’s blood analyzers used in POC settings with low-
not be compatible with the laboratory’s information to medium-volume testing use self-contained reagent
management system. In these cases, results need to be cartridges. Single-use cartridges contain the calibration
manually entered into the medical record or labora- solution and miniaturized electrochemical sensors that
tory information management system, increasing the are needed for analysis. These single-use systems are
propensity for transcription error. Transcription errors portable and easy to transport. They are recommended
can compromise patient care, especially if the error for settings with a test volume of less than 10 samples
goes unrecognized and the patient is treated on erro- per day. Sensor electrodes in single-use cartridge sys-
neous results. tems are self-calibrating and can flag calibration errors.
There may also be duplication in testing, which is The analyzer and electrodes require little, if any, main-
costly and not efficient. Patients may have specimens tenance and a calibration is performed before any mea-
collected and tested in the core laboratory while hav- surement is released. In the event of a calibration error,
ing the same or similar tests performed via POC. POC the calibration is flagged and the results are suppressed.
testing, although convenient, uses many consumable Problems due to blockage from fibrin clots are confined
cartridges and supplies, which can add cost to the to the cassette in use. The cartridge containing the

9781449601942_CH06_PASS02.indd 168 01/10/14 6:44 PM


Currently Available Analyzers and Units Used for Blood Gas Analysis 169

waste, blood, and calibration fluid is removed from the may also be conducted manually using individual gas
analyzer and disposed of in a biohazard container. ampules that contain aqueous control solutions that are
In settings with medium- to high-volume sample equilibrated with gas mixtures. Today, most analyzers
testing, a multiuse cartridge system is used. These car- utilize automatic on-board quality control materials
tridges can be customized to the specific analyte menu that simplify the process and reduce operator work-
and to the volume of testing. The number of samples load, while producing a more consistent quality con-
measured on a cartridge may vary from 25 to 750. Once trol program. Electronic QC requires no user input and
loaded onto the analyzer, the cartridge has an in-use automatically detects, corrects, and monitors the status
life of between 14 and 30 days. For cost effectiveness, of the analyzer’s internal electronics.
the appropriate size cartridge is selected to meet the Because QC can be automatically scheduled into the
unit’s workload volume. analyzer, it doesn’t get delayed if the healthcare pro-
There are also larger analyzers that provide sensor vider is attending to patient care issues. The automatic
electrodes and reagents, such as calibrators, wash solu- QC can be scheduled to run three levels at three times
tions, and quality control materials in either a modular a day; the operator must still verify the results. Further,
format or as individual reagent containers. These sys- operators cannot attempt to analyze expired QC or
tems include a closed waste system and feature reduced incorrect QC materials, another concern with older
downtime compared with earlier models. These larger testing systems. In the past, operators may have had
analyzers may require more maintenance to replace to rerun a calibration or QC to obtain values that are
or to remembrane sensor electrodes, replace tubing or accepted or are in range. This practice delayed patient
peristaltic pumps, or replace a gas cartridge when com- care and perhaps compromised patient results, and also
pared to the smaller volume analyzers. Thus, the larger added to the cost of the test.
analyzers may require additional technical support and
expertise.
As discussed previously in this chapter, modern
Currently Available Analyzers and
analyzers utilize a variety of technologies to mea- Units Used for Blood Gas Analysis
sure and report results. These include potentiometry, In the early days of blood gas analysis, there were four
amperometry, and fluorescence. Ion-selective elec- major equipment manufacturers: Corning (now Siemens),
trodes are used to measure the electrolytes, Na+, K+, Instrument Laboratories (IL), Nova Biomedical, and
Ca2+, Cl–, and Mg2+. The hematocrit is measured using Radiometer. These four manufacturers still exist, and
conductivity, and hemoglobin is measured using spec- there are several other vendors worldwide, including
trophotometry. CO-oximetry measurement is based on Roche.
optical measurements of analytes at a number of wave- Each manufacturer has product lines that meet
lengths of light. the needs of the testing facility, based on the volume
of testing, test menu, and speed of analysis. There is
Laboratory Processes: Calibration also flexibility when choosing the degree of operator-
initiated and internal quality control, calibration, and
and Quality Control verification. Whereas surgery requires a POC analyzer
Calibration allows the analyzer responses to be set that produces fast and accurate results, the needs of
and adjusted to a known standard reference. Newer the neonatal ICU are directed more toward trend-
analyzers use aqueous tonometered solutions for ing, and what the patient’s results are from day to day.
calibration. These are available in sealed units. A one- For example, smaller critical care units may opt for
point calibration adjusts the electrode to one level, a bench top unit, such as Siemen’s 405, which offers
either high or low. It is frequently performed and is tests for blood gases, glucose, hemoglobin, hematocrit,
automatically conducted by some analyzers before calcium, electrolytes, and a full co-oximeter panel.
each measurement is released. A two-point calibration The QC is automatically run by the analyzer, but does
adjusts the electrode at two levels, high and low, and require operator verification. Larger volume critical
is set by the operator at intervals ranging from every 2 care units may choose larger analyzers that can accom-
to every 24 hours. Calibrations can be preset at sched- modate a higher test volume, such as the Siemens 1265.
uled intervals. Adult medical and surgical critical care units may rely
Internal quality control is designed to detect and primarily on specific parameters, such as the blood
monitor errors in the testing procedure, but will not gases, whereas pediatric testing in neonatal units often
detect errors in sample collection and handling. Internal requires a broader test menu. There is also flexibility
QC assures the operator that the reagents and analyzer in the cartridge size; for example, Siemens offers a
are operating correctly; it will identify many analyti- 450-specimen and a 700-specimen cartridge for the
cal errors. The frequency of QC depends on the level of 405 series analyzers. Again, a facility can choose the
testing done and the specifications of the manufacturer more cost-effective and appropriate cartridge for its
and standards of the accrediting agencies. Internal QC testing setting.

9781449601942_CH06_PASS02.indd 169 01/10/14 6:44 PM


170 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

Larger volume analyzers generally require increased malfunctions. However, because of these technology
maintenance, which includes checking the electrodes, checks, the analysis time is extended from 1 minute
calibrating the barometer, and deproteinizing the elec- to approximately 4 minutes from aspiration to result.
trodes. Linearity studies, calibration verification, and The IL analyzers run over 100 QC each day on average,
other surveys required by the College of American which further assists with compliance and consistency
Pathology (CAP) are also required throughout the year. of results.
However, even large-volume modern blood gas ana- Other advantages of modern analyzers include the
lyzers require significantly less manual maintenance concept that the instrument is continuously up and
than did their predecessors. Whereas older analyzers running. Clogged aspiration probes, electrode drift,
required pathways to identify the problem, today’s or replacing electrode membranes used to be labor-
analyzers offer more self-maintenance. The testing car- intensive procedures requiring a skilled professional.
tridge contains the reagents and components, in place Upon completion of such tasks, a calibration and full
of reagent bottles and ampules that would have to be QC were required, which often led to instrument down
replaced. Cartridge-based systems provide flexibility time and delays for patient results.
in the test menu and can be selected based on the test- Less staff time is needed to test daily QC and to
ing volume. Because cartridges last 2 to 4 weeks, the install and recalibrate gas cylinders, and there is a
menu and type of cartridge can be adjusted to meet the more efficient mechanism to document errors. For
needs of the facility. The electrode module is similar to IL analyzers, new electrodes are included in each
that of earlier units, and therefore requires appropriate GEM cartridge, so there is no need to remembrane or
maintenance. replace failed electrodes. Other advantages include
By choosing the same manufacturer, units can be integrated sample collection devices. For example, the
selected that meet the needs of the core laboratory, GEM systems use a flexible heparin tube for pediatric
critical care units, surgery, neonatal care units, and patients whose volume is sufficient to perform blood
emergency room. Consolidation to a single vendor as gases, and also electrolytes and other analytes.
compared to using different analyzers and vendors The GEM system also offers an add-on module for
for different departments is both cost effective and CO-oximetry analysis (GEM-OPL), which is interfaced
beneficial for inventory management. There are less into the main testing unit. The GEM-OPL uses six
items to inventory and to order and less products to be wavelengths of light, but does not require hemolysis
knowledgeable about. Further, there is consistency in of the sample. It uses thin-slide translucency technol-
the results from the POC units to the larger units that ogy that requires only 50 µL of blood and a disposable
may be used in the respiratory department or labora- cuvette. The full CO-oximetry panel is reported within
tory. The ability to communicate with one vendor and 10 seconds.
to become familiar with its products minimizes issues Roche’s line of analyzers includes the cobas b 221,
with testing. Further, there is a greater agreement with which is also a multiparameter analyzer for blood
patient values when the same product line or methodol- gases, CO-oximetry, electrolytes, and metabolites. It
ogy is used. is designed to be a high-volume analyzer, and is not
The Siemens products also interface into the considered to be a portable unit. These units also use
laboratory’s information system, so that the operator reagents to generate the gases, eliminating metal tanks
can review historical data, tracking, test ordering and for O2 and CO2..Roche’s cobas b 123 is a POC system
canceling, and quality audits. that features a mobile blood gas analyzer with a selec-
The Instrument Laboratory (IL) also offers products tion of 15 parameters. The system uses a patented
with POC and traditional central core laboratory capa- thick-film sensor technology and a broad test menu
bilities. The GEM 3000 series provides self-contained with results within 2 minutes. Another feature of the
plug-in cartridges, eliminating the need to prepare cobas b 123 is its four-level clot protection system as
reagents and to pump in the gas mixtures. There are well as automatic linearity testing and calibration.
also important quality control features, including IL’s Roche’s Electronic Quality Assurance Program (eQAP)
proprietary Intelligent Quality Management (IQM) assists with QC, regulatory compliance, and the abil-
System. Quality control between the central laboratory ity to participate in peer review and benchmarking of
and POC is more consistent and standardized through quality control.
the IQM system. Auto-validation is another feature Radiometer, manufacturer of the ABL line of analyz-
of the IL analyzers; the system runs a fully automated ers, patented its “First Automatic” technology, designed
QC sequence immediately after the aspiration of each to improve workflow by improving sample collection,
patient sample and before test results are released. In processing, analysis, and reporting. Its goal is to pro-
the past, it was necessary to aspirate blood gases two vide a system with fewer preanalytical errors; better
times in a row to determine precision. Other features identification of patient, sample, and results; and less
of the IL system include enhanced clot detection, paperwork. Radiometer’s ABL 800 Flex analyzer offers
low sample warning flags, and detection of biosensor a comprehensive test menu of 18 analytes and rapid

9781449601942_CH06_PASS02.indd 170 01/10/14 6:44 PM


TABLE 6-10
Currently Available Analyzers

9781449601942_CH06_PASS02.indd 171
Measured Analytes

Manufacturer Model Category Blood Gas Electrolytes Metabolites and Other Tests CO-Oximetry Volume Features

Siemens RAPIDLab 1200 POC pH, pCO2, Sodium Glucose, lactate, neonatal total Total hemoglobin (tHb), Medium to Clot detection and clearance
Systems pO2 (Na+), bilirubin deoxyhemoglobin (HHb), high sampling system, automatic
Potassium oxyhemoglobin (O2Hb), QC, comprehensive menu
(K+), Calcuim Oxygen saturation (sO2),
(Ca2+), Carboxyhemoglobin
Chloride (Cl–) (COHb), Methhemoglobin
(MetHb)

RAPIDPoint POC pH, pCO2, Na+, K+, Hematocrit Low to Single reagent cartridge;
350 pO2 Ca2+, Cl– medium dialysate mode;
75–120 μL sample

RAPIDPoint 340 POC pH, pCO2, Low to Single reagent cartridge;


pO2 medium dialysate mode; 75–120 μL
sample

RAPIDLab 248 Critical care pH, pCO2, Critical care Small sample size, 50–95
pO2 testing μL; analysis in 45 seconds

RAPIDLab 348 Critical care pH, pCO2, Na+, K+, Hematocrit Critical care Small sample size, 50–95
pO2 Ca2+, Cl– testing μL; analysis in 50 seconds

RAPIDLab 348 POC pH, pCO2, Na+, K+, Hematocrit Dialysate mode; low volume;
pO2 Ca2+, Cl– enhanced operator features

RAPIDPoint 500 POC pH, pCO2, Na+, K+, Glucose, lactate tHb, HHb, O2Hb, sO2, Data management system
pO2 Ca2+, Cl– COHb, MetHb, neonatal
total bilirubin

Instrument GEM Premier POC pH, pCO2, Na+, K+, Glucose, lactate, neonatal total tHb, HHb, O2Hb, sO2, Self-contained, multiuse
Laboratory (IL) 4000 pO2 Ca2+, Cl– bilirubin, hematocrit COHb, MetHb cartridges, Intelligent Quality
Management (IQM) System

(continues)
Currently Available Analyzers and Units Used for Blood Gas Analysis
171

01/10/14 6:44 PM
172

9781449601942_CH06_PASS02.indd 172
TABLE 6-10
Currently Available Analyzers (Continued)

Measured Analytes

Manufacturer Model Category Blood Gas Electrolytes Metabolites and Other Tests CO-Oximetry Volume Features

Instrument GEM Premier POC pH, pCO2, Na+, K+, Glucose, lactate, hematocrit Self-contained, multiuse
Laboratory (IL) 3500 pO2 Ca2+, Cl– cartridges, IQM

GEM Premier POC and pH, pCO2, Na+, K+, Glucose, lactate, hematocrit, tHb, HHb, O2Hb, sO2, Large Comprehensive test menu;
3000 centralized pO2 Ca2+, Cl– prothrombin time (PT), activated COHb, MetHb volume customizable cartridges;
testing partial thromboplastin time can add coagulation and
(APTT), activated clotting time CO-oximetry units
(ACT), activated clotting—time
low range (ACT-LR)

Roche cobas b 123 Critical care pH, pCO2, Na+, K+, Glucose, lactate, hematocrit tHb, HHb, O2Hb, sO2, Medium Results within 2 minutes;
POC pO2 Ca2+, Cl– COHb, MetHb to small thick-film sensor technology
volume
CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

cobas b 121 Critical care pH, pCO2, Small sample size


pO2

cobas b 221 Critical care pH, pCO2, Na+, K+, Glucose, lactate, hematocrit, tHb, HHb, O2Hb, sO2, Medium to
system pO2 Ca2+, Cl– BUN, bilirubin COHb, MetHb high

Radiometer ABL 800 FLEX POC and pH, pCO2, Na+, K+, Glucose, lactate, creatinine, tHb, HHb, O2Hb, sO2, Medium to First automatic and FlexQ
centralized pO2 Ca2+, Cl– bilirubin COHb, MetHb high volume features
testing

ABL 90 FLEX Acute care pH, pCO2, Na+, K+, Ca2+ Glucose, lactate, bilirubin tHb, HHb, O2Hb, sO2, Medium Comprehensive acute care
pO2 COHb, MetHb volume panel, 35-second turnaround
time

ABL 80 FLEX pH, pCO2, Na+, K+, Glucose, hematocrit tHb, HHb, O2Hb, sO2, Medium to
pO2 Ca2+, Cl– COHb, MetHb low volume

Note: Table is not comprehensive and includes only measured, not derived, parameters.

01/10/14 6:44 PM
References 173

analysis. Its FLEXQ module automatically identifies, 7. Klæstrup E, Trydal T, Pedersen JF, Larsen JM, Lundbye-
mixes, and measures up to three samples in succession. Christensen S, Kristensen SR. Reference intervals and age and
gender dependency for arterial blood gases and electrolytes in
Although some blood gas systems permit the inte- adults. Clin Chem Lab Med. 2011;49(9):1495-1500.
gration of POC results into the electronic medical 8. Crockett AJ, McIntyre E, Ruffin R, Alpers JH. Evaluation of
record, other systems have this capability only for lyophilized heparin syringes for the collection of arterial blood
the centralized laboratory or respiratory care unit. for acid base analysis. Anaesth Intensive Care.1981;9(1):40-42.
Concerns continue with the ability of some analyzers to 9. Thomson JM. Blood collection and preparation techniques:
Pre-analytical variation. In: Jespersen J, Bertina RM, Haverkate
handle fibrin clots, which relates to the expertise of the F, eds. EACT Assay Procedures: A Manual of Laboratory
individual drawing the arterial blood sample. Cleaning Techniques. Dordrecht, Netherlands: Kluwer Academic;
the arterial line to avoid diluted samples and avoiding 1992:13-20.
clots within the specimen are dependent upon each 10. Pruden EL, Siggaard-Andeson L, Tietz NW. Blood bases and pH.
person’s training. Although the newer analyzers can In: Burtis CA, Ashwood ER, eds. Tietz Fundamentals of Clinical
Chemistry. Philadelphia: WB Saunders; 1996:211-223.
detect clots and bubbles, a clot will still cause problems 11. Adams AP, Morgan-Hughes JO, Sykes MK. pH and blood-gas
with the system until it is removed. analysis. Methods of measurement and sources of error using
Today many hospitals use POC instruments in electrode systems. Anaesthesia. 1967;22(4):575-597.
conjunction with stand-alone instruments to verify 12. Beetham R. A review of blood pH and blood-gas analysis. Ann
results obtained on POC analyzers. Both POC and Clin Biochem. 1982;19(Pt 4):198-213.
13. Severinghaus JW, Astrup PB. History of blood gas analysis.
stand-alone analyzers are subject to Clinical Laboratory I. The development of electrochemistry. J Clin Monit. 1985;
Improvement Amendments of 1988 (CLIA) regulations. 1(3):180-192.
Some of the currently available analyzers are summa- 14. Severinghaus JW, Astrup PB. History of blood gas analysis. III.
rized in Table 6-10. Carbon dioxide tension. J Clin Monit. 1986;2(1):60-73.
The accuracy and precision of results are related 15. Reynafarje B, Costa LE, Lehninger AL. O2 solubility in aque-
ous media determined by a kinetic method. Anal Biochem.
to the degree of technology, but equally important is 1985;145(2):406-418.
the expertise of the testing personnel. Testing in the 16. Gehring H, Duembgen L, Peterlein M, Hagelberg S, Dibbelt L.
central laboratory is conducted by appropriately edu- Hemoximetry as the “gold standard”? Error assessment based
cated laboratory professionals who maintain regulatory on differences among identical blood gas analyzer devices of five
compliance. Nonlaboratory personnel who use POC manufacturers. Anesth Analg. 2007;105(6 Suppl):S24-S30.
17. Toobiak S, Sher EA, Shaklai M, Shaklai N. Precise quantification
systems may not be fully cognizant of the influence of of haemoglobin in erythroid precursors and plasma. Int J Lab
physiologic and analytical factors on the final result, Hematol. 2011;33(6):645-650.
which could lead to improper treatment decisions. Up 18. Kazmierczak SC. Laboratory quality control: Using patient data
to 68% of errors in blood gas measurements in point- to assess analytical performance. Clin Chem Lab Med. 2003;
of-care are related to sample collection, handling, and 41(5):617-627.
19. Siggaard-Andersen O. The van Slyke equation. Scand J Clin Lab
preparation that invalidate the results regardless of the Invest Suppl. 1977;146:15-20.
technology of the analyzer. 20. Lang W, Zander R. The accuracy of calculated base excess in
blood. Clin Chem Lab Med. 2002;40(4):404-410.
References 21. Albert V, Subramanian A, Rangarajan K, Pandey RM. Agreement
of two different laboratory methods used to measure electrolytes.
1. Department of Health and Human Services, Health Care J Lab Physicians.2011;3(2):104-109.
Financing Administration, Public Health Service. Clinical 22. Ronkainen NJ, Halsall HB, Heineman WR. Electrochemical bio-
laboratory improvement amendments of 1988; final rule. sensors. Chem Soc Rev. 2010;39(5):1747-1763.
Federal Register. 1992 February 28. Available at: https://www. 23. D'Orazio P. Biosensors in clinical chemistry. Clin Chim Acta.
federalregister.gov/clinical-laboratory-improvement-program. 2003;334(1–2):41-69.
Accessed June 14, 2014. 24. Borisov SM, Wolfbeis OS. Optical biosensors. Chem Rev. 2008;
2. National Committee for Clinical Laboratory Standards (NCCLS). 108(2):423-461.
Procedures for the collection of arterial blood specimens, 25. Carraro P, Plebani M. Errors in a stat laboratory: Types and fre-
1999. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ quencies 10 years later. Clin Chem. 2007;53(7):1338-1342.
PMC87384. Accessed June 26, 2014. 26. Bonini P, Plebani M, Ceriotti F, Rubboli F. Errors in laboratory
3. Browning JA, Kaiser DL, Durbin CG Jr. The effect of guidelines medicine. Clin Chem. 2002;48(5):691-698.
on the appropriate use of arterial blood gas analysis in the inten- 27. Biswas CK, Ramos JM, Agroyannis B, Kerr DN. Blood gas analy-
sive care unit. Respir Care. 1989;34(4):269-276. sis: Effect of air bubbles in syringe and delay in estimation. Br
4. Jordan A. Blood gas: A brief anecdotal history by one who Med J (Clin Res Ed). 1982;284(6320):923-927.
has been there. MLO-online. 2012. Available at http://www. 28. Davies MW, Mehr S, Morley CJ. The effect of draw-up volume
mlo-online.com/articles/201209/blood-gas-a-brief-anecdotal on the accuracy of electrolyte measurements from neonatal arte-
-history-by-one-who-has-been-there.php. Accessed July 10, rial lines. J Paediatr Child Health.2000;36(2):122-124.
2014. 29. Weibley RE, Riggs CD. Evaluation of an improved sampling
5. Paxton A. Blood gas analyzers—the old and the new. CAP method for blood gas analysis from indwelling arterial catheters.
Today. August 2007. Available at: http://www.cap.org/apps/ Crit Care Med. 1989;17(8):803-805.
portlets/contentViewer. Accessed June 25, 2014. 30. National Committee for Clinical Laboratory Standards (NCCLS).
6. Shapiro BA, Mahutte CK, Cane RD, Gilmour IJ. Clinical perfor- C46-P Blood gas and pH analysis and related measurements.
mance of a blood gas monitor: A prospective, multicenter trial. 2000. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/
Crit Care Med. 1993;21(4):487-494. PMC87384. Accessed June 26, 2014.

9781449601942_CH06_PASS02.indd 173 01/10/14 6:44 PM


174 CHAPTER 6  Blood Gas and Critical Care Analyte Analysis

31. Bisson J, Younker J. Correcting arterial blood gases for tem- 36. Kost CJ. Critical limits for urgent clinical notification of US
perature: (When) is it clinically significant? Nurs Crit Care. medical centers. JAMA. 1990;263(5):704-707.
2006;11(5):232-238. 37. Schoenmakers CH, Naus AJ, Vermeer HJ, van Loon D, Steen G.
32. Westgard JO, Klee GG. Quality management. In: Burtis CA, Practical application of Sigma Metrics QC procedures in clini-
Ashwood ER, eds. Tietz fundamentals of clinical chemistry, cal chemistry. Clin Chem Lab Med. 2011;49(11):1837-1843.
Philadelphia: WB Saunders; 1996:211-223. 38. Harel O, Schisterman EF, Vexler A, Ruopp MD. Monitoring
33. O’Kane MJ, McManus P, McGowan N, Lynch PL. Quality error quality control: Can we get better data? Epidemiology. 2008;
rates in point-of-care testing. Clin Chem. 2011;57(9):1267-1271. 19(4):621-627.
34. Piva E, Plebani M. Interpretative reports and critical values. Clin 39. Westgard JO. Internal quality control: Planning and implementa-
Chim Acta. 2009;404(1):52-58. tion strategies. Ann Clin Biochem. 2003;40(Pt 6):593-611.
35. Rensburg MA, Nutt L, Zemlin AE, Erasmus RT. An audit on
the reporting of critical results in a tertiary institute. Ann Clin
Biochem. 2009;46(Pt 2):162-164.

9781449601942_CH06_PASS02.indd 174 01/10/14 6:44 PM

You might also like