Download Blood Testing for the Support of Critically Ill Patients

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Blood Testing for the Support of Critically Ill Patients
Terry L. Shirey, Ph.D.
Nova Biomedical
200 Prospect St.
Waltham, MA 02154
[email protected]
Abstract
The practice of critical care medicine has recently been advanced via the availability
of key biochemical test results at the patient's bedside within the brief period in time
when they can be used to guide resuscitation and cardiovascular stabilization effectively.
Frequently the menu of key tests, referred to as a critical care profile (CCP), needs to be
available to the attending clinician within 5 minutes if it is to affect therapeutic strategy in
real time.
This review is an update of an article that was published in 1995.79 It briefly
describes which tests should be considered for a CCP, and identifies several clinical
settings (e.g. acute chest pain, cardiac surgery, and circulatory shock) where a CCP may
dramatically affect patient outcomes. Locations benefiting from CCP capability include
the Emergency Department (ED), the operating room (OR) and the intensive care unit
(ICU).
Need for a CCP
Physicians treating a patient undergoing cardiopulmonary bypass who arrests during
surgery, a patient with non-penetrating trauma entering the Emergency Department, or a
patient in the ICU starting to experience cardiac irregularity have a common need-immediate biochemical information. Traditionally clinicians, not willing to wait for
laboratory results because of the time required for their availability, intervene on behalf of
an emergent patient by initiating treatment based on history presentation, and experience.
The advent of whole blood analysis and point-of-care (POC) testing has opened up a
new approach to caring for critically ill patients: the ability to provide a CCP with a total
turnaround time (TAT) of 5 minutes; i.e., from the time the clinician asks what the
patient's most time-vulnerable critical biochemical values are to the time he knows the
answers.
What tests belong on a CCP?
Which tests should be included in a CCP? Glycohemoglobin? A transaminase?
Serum albumin? It would be hard to defend a TAT of 5 minutes for these tests. On the
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other hand, are blood gases the only tests required. A common denominator for tests on a
CCP is their marking the integrity of the ‘energy pathway’. The ‘energy pathway’ is the
sequence of events ensuring that adequate oxygen and glucose enter the blood, that the
cardiovascular system perfuses the blood to the tissues, and that the oxygen and glucose
get from the capillary beds to the cells where they are metabolized to ATP. The brief
TAT required for a CCP in a hemodynamically unstable patient is apparent when one
realizes that within 10 seconds of oxygen deprivation a person loses consciousness, and
within 6 minutes creatine phosphate and ATP energy reserves have been sufficiently
drained to threaten permanent brain damage. From the time that inadequate oxygen is
available to the cells, oxygen debt accrues translating into direct tissue damage from ATP
inadequacy and indirect tissue damage from reperfusion injury and excessive
inflammatory response.
The CCP suggests whether the tissues are receiving adequate glucose and oxygen
and, if not, why availability has been compromised. PaO2 and PaCO2 help to determine
diffusion and perfusion at the lung. Hematocrit or hemoglobin determine whether there
is adequate carrier to get oxygen to the tissues. The cations [potassium (K+), ionized
calcium (iCa), and ionized magnesium (iMg)] bathing the heart and the vasculature help
ensure sufficient cardiac output and blood pressure for perfusion to the tissues. Sodium
is an indicator of fluid distribution between capillary and cell. Markers for intracellular
mileaus’ adequacy to promote the metabolism of the oxygen and glucose to ATP, and to
minimize tissue damage induced by hypoxia and endotoxin include pH and iMg.
Today the results of such a CCP, obtained from a single sample of < 200 uL of whole
blood, can be available to the attending clinician within 5 minutes of his request at the
point of care.
Glucose
Approximately 85% of ingested glucose is stored as glycogen in the liver to be
gradually released with time between meals to feed the tissues. Patients with insufficient
glycogen, e.g. those who are starved, neonates with small glycogen reserves, or patients in
end-state shock are candidates for potentially debilitating hypoglycemia. In addition, a
clinician may treat hyperglycemia and/or hyperkalemia with insulin. While frequently
accompanied by glucose, insulin treatment could result in low blood sugar.
Hyperglycemia is also a concern in these patients. The epinephrine response typical
for very ill patients (trauma, stress, surgery, etc.) serves as a natural glucose generator.
Intravenous dextrose, reduction of the insulin response by hypothermia, and osmotic loss
of water to the glomerular filtrate as glucose starts to spill at the kidney further
concentrate the blood glucose. The rate of increase of glucose may be significant; e.g. an
increase from 144 to 774 mg/dL in 95 minutes having been reported for a non-diabetic
during abdominal aortic surgery.1 Nonketotic hyperglycemic patients frequently exhibit
plasma glucose concentrations greater than 1000 mg/dL.2 Although lethal concentrations
of glucose have been experienced by some cardiopulmonary bypass (CPB) patients 3,
much milder elevations of glucose threaten vital tissues (e.g. the Sustantia Nigra portion
of the brain) in the event of inadequate oxygenation.4 Sieber5 and Van den Berghe80
suggest that damage may occur under hypoxemic conditions at glucose < 180-250
mg/dL. Many critically ill patients suffer regional, if not global hypoxemia. Maintaining
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adequate, but not excessive glucose in the critically ill patient makes glucose a strong
candidate for the CCP.
PaO2 and Hct (or Hb)
Monitoring gas exchange at the lung can help predict adequacy of ventilation and
lung perfusion. PaO2 is the most sensitive indicator for the adequacy of diffusion of
oxygen across the lung. Under conditions of reduced diffusion, PaO2 falls from 95-100
mm Hg (normal) to about 60 mm Hg during the time that oxyhemoglobin decreases from
about 98% to 92%. Should a patient be receiving supplemental oxygen, PaO2, and not
oxyhemoglobin, can quantify the amount of oxygen absorbed by the lung. At any
position in the circulatory system, PaO2 reflects more sensitively the O2 available to the
tissues than oxygen saturation. PaO2 is also the measurement by which other technology
is standardized (e.g. pulse oximeters).
Hematocrit (Hct) or hemoglobin (Hb)
Hct or Hb (very comparable in clinical utility) gives a measure of oxygen transport
capability. Should hemoglobin derivatives be included in the CCP? Testing for
carboxyhemoglobin in victims of carbon monoxide exposure presenting to the ED may be
important occasionally. Whether the presence of methemoglobin belongs on a CCP has
yet to be determined, relatively low levels having been reported following therapy with
nitrous oxide.6
Lactate
Is it sufficient to know that adequate oxygen is crossing the lung and that it has
sufficient carrier to get it to the tissues? Variations in oxygen consumption along with
the possibility of oxygen shunting suggest more information is needed to ensure adequate
oxygenation. Current approaches attempting to assure adequate oxygenation include
delivering oxygen (DO2) at least at twice the rate that it is being consumed (VO2), or
titering therapy to optimal supranormal physiologic end points (e.g. DO2 > 600
mL/min/m2 and VO2 to 167 mL/min/m2).7 However, many of the most critically ill
patients, such as those with sepsis, adult respiratory distress syndrome (ARDS), and
trauma, do not have global delivery-dependent hypoxia. This may in part be due to
regional oxygen shunting.8-10 In addition, the most accurate means of determining DO2
and VO2 is quite invasive, requiring a pulmonary artery catheter. Multiple measurements
representing several sources of error make DO2 and VO2 approximations at best.
An alternative approach to determining whether or not tissues are receiving adequate
oxygen is to measure lactate. Lactate, the end product of anaerobic glycolysis, is
clinically sensitive to global and, to some extent at least, regional oxygen debt.
Inadequate oxygen to tissues or an organism correlates directly with morbidity and
mortality. Not only does it result in reduced concentrations of high-energy metabolites
(creatine phosphate and ATP), it also sets the stage for an inflammatory reaction11-13 or
for reperfusion injury should oxygen be readmitted to the affected system14. These in
turn damage the vascular endothelia which may lead to organ failure or systemic
inflammatory response syndrome (SIRS) with attendant morbidity and mortality.
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Interpreting an elevated blood lactate concentration will require additional clinical
information. In addition to hypoxia, the degree of lactate elevation may reflect any of the
following: inadequate lactate metabolism via a severely compromised liver, the
concentration of blood glucose during the hypoxia15, the cause of the hypoxia (e.g.
sepsis, exercise, seizure, acute myocardial infarction, etc.)16, treatment with lactatedRinger's solution, or sudden release of pent-up lactate as perfusion is restored (washout
phenomenon).
In a general sense, lactate provides an early indicator for inadequate perfusion and
oxygenation, a semiquantitative value of tissue oxygen deficiency, a prognostic indicator
for admitting and triaging patients, and a marker for assessing the success of therapy. In
addition, it holds the promise for supporting transfusion decisions, recognizing donor
organ viability, backing off of positive end-point expiratory pressure or catecholamine
therapy, supporting burn resuscitation, and even aiding in the decision for cesarean
section (scalp lactate).
The lactate assay has been available for many years. Why should it receive increased
attention now? It can now be performed on a whole blood sample, eliminating the
centrifugation step required for serum or plasma analysis.17 This translates into a
dramatically reduced TAT allowing lactate to assume a significant position in the CCP
rather than to be viewed as archival information. It is the only marker which may identify
regional as well as global oxygen deficiency.
Potassium and calcium
The all-important perfusion pump, the heart, relies on regular conduction and
adequate contraction to maintain cardiac output. The resting potential on nerve and
muscle cell membranes is set by the extracellular concentration of potassium ions; the
threshold potential by extracellular ionized calcium (iCa).2 Normally the difference
between these two potentials is about 20 millivolts. An electrical impulse entering the
cell must exceed the difference in the two potentials for the cell to "fire" (or go to action
potential), resulting in a contraction. Should either of the potentials vary with respect to
the other, i.e. should extracellular K vary with respect to extracellular iCa, the ability of
the cell to fire will be altered. An arrhythmia may develop. If, for example, a patient
becomes hyperkalemic with the attending decrease in resting potential, the therapy may
be calcium infusion to reset the threshold potential thereby stabilizing the membrane.
Frequently only K is monitored in patients when in fact the ratio of the two cations,
K/iCa, is important to physiologic function.
In addition to measuring the appropriate electrolytes, four other points should be
considered. (1) The "ionized" or free form of the electrolyte is the physiologically active
form. In 1934, McClean and Hastings18 demonstrated that iCa, and not total calcium
concentration (TCa), is responsible for the strength of muscular contraction. (2)
Monitoring ionic versus total electrolyte is particularly important in critically ill patients
due to the rapidly changing ligand population. In the unstable, critically-ill patient,
iatrogenically administered anions, such as citrate in blood products or bicarbonate for the
treatment of acidosis, and physiologically generated ligands such as lactate or phosphate
may bind the cations rendering them physiologically inactive while the total concentration
of the electrolyte remains virtually the same. (3) Pharmacologic responses may be
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cation-activity dependent. Several authors report that the pharmacologic effects of
various cardiovascular medications are cation dependent.19-21 (4) Measuring a single
cation without considering other analytes may lead to inappropriate action. For example,
a patient with a plasma potassium concentration of 4.0 mmol/L is severely hypokalemic if
the patient has a pH of 7.0. Reference was made earlier to the dependence of K on iCa
for an appropriate physiologic response.
Magnesium
Ionized magnesium also plays a very important role in cardiovascular function. The
electrocardiogram demonstrates that each of the three major cations; K, iCa, and iMg,
play a role in rhythmic performance22. Ionized magnesium controls electrolyte balance
across nerve and muscle cell membranes.23,24 Mg is required as a cofactor for ATPase
function and thereby affects K and iCa distribution across these membranes. Minimal
replenishment of K occurs when infusing K-rich fluid into a hypomagnesemic patient.
Appropriate levels of iMg, as well as K and iCa, are required for the proper activity of
many cardiovascular drugs. For example low iMg, which allows more iCa into myocytes,
is accomplishing what digoxin does. The additive effect may lead to toxic digoxin
reactions, even when digoxin in within its therapeutic range.
Having adequate levels of iMg is important to tissue integrity. As a cofactor for over
325 enzymes, iMg is involved heavily in carbohydrate, lipid, and nucleic acid
metabolism. It is involved in virtually all high-energy reactions. Not only will cellular
metabolism suffer with inadequate iMg, but also, cells will be more vulnerable to oxygen
free radical damage and the inflammatory response.
Dietary magnesium, ligand-binding (as with calcium), and kidney function (filtering
ability of the glomerulus and the reabsorption ability of the distal tubules) are primarily
responsible for acute metabolic handling of plasma iMg.25
Although intracellular total magnesium concentration (TMg) is usually 20 to 30 times
plasma TMg, it has been shown by 31P-NMR, micro iMg electrode, and fluorescent
molecular probe studies that intracellular iMg activity is comparable to that of plasma or
serum.26-30 Also, data suggest that magnesium passage through the cell membrane may
be weakly- or non-facilitated and spontaneous.26,31,32 Comparable intra-and
extracellular iMg activities with ready transmembrane passage suggest that plasma/serum
iMg activities could represent the active fraction of magnesium inside as well as outside
the cell.
Clinical settings where a CCP may be important
Settings where rapid changes in a patient's hemodynamic status may occur include the
Emergency Department (ED), Operating Room (OR), and the Intensive Care Unit (ICU).
Emergency treatment, admission, and triage decisions are made in the ED. Frequently
quantities of fluid are administered to a patient in the OR dramatically altering CCP
analytes in the patient's blood . Surveillance and early response to rapid changes in the
patient's condition are considerations in the ICU. The following are emergency medical
settings where tests from a CCP have been reported to better support treatment strategies.
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Emergency Department
Critically ill patients presenting to the ED include those having experienced trauma,
cardiac arrest, acute myocardial infarction (AMI), and occult disease. A rapid CCP at
ED entry may guide emergency treatment, admission, and triage strategies.
• Trauma
Penetrating trauma accounted for about 30% of the trauma patients seen in the ED in
a study reported by Frankel.33 These patients were treated in the OR within 45 minutes
of hospital entry; too soon to have results from the central laboratory to guide therapy.
Providing a partial CCP in the ED demonstrated that 39% of these patients had abnormal
iK (14% with blunt trauma), 54% had abnormal pH (26% with blunt trauma), and 42% a
hematocrit < 33% (14% with blunt trauma). Glucose levels following acute brain injury
have been associated with greater severity of injury and poor neurologic outcome.34,35
Ionized magnesium has also been found to decrease relative to the severity of head
trauma.36
In a study of over 4000 admissions to the Johns Hopkins Hospital ED, lactate levels
predicted survival and correlated with Injury Severity Index and the Glasgow Coma
Score.37 The prognostic value of lactate for hospital admission and mortality led Aduen
et al38 to endorse bedside testing for ED and ICU patients. Abramson et al39 relied on
lactate to determine whether their trauma patients should be invasively monitored.
Should lactate levels fail to normalize in 24 hours, this group would return their trauma
patients to surgery to look for missed injury realizing that survival of their patients
decreased dramatically if the lactate value remained elevated. Intracranial pressure (ICP)
from head trauma was also associated with elevated lactate levels.40 Treatment with
fluids and inotropes, neither exacerbating the ICP, led to better outcomes.
• Cardiac Arrest
Cardiac arrest is a medical emergency with very few successful outcomes, 1-3% of
patients leaving the hospital alive or unimpaired.14,41 Denying the brain oxygen leads
rapidly to permanent damage or death. Carden et al42 determined the "downtime" of the
heart from the magnitude of the lactate value to guide them in the aggressiveness of their
resuscitation efforts. The risk of reperfusion injury with successful resuscitation is great,
many patients dying 48-72 hours following successfully reestablishing normal rhythm.4345 Predicting the level of oxygen debt could influence resuscitation measures. If the debt
is large, perhaps using ablative materials prior to re-introducing oxygen into the system
could ameliorate reperfusion injury.44 Safar et al43 have experimented with resuscitation
using fluids, initially containing no oxygen, but ablative materials to rid the system of free
radical substrates before re-introducing oxygen to try to reduce reperfusion injury.
A study reported by Urban et al46 suggests that major electrolyte imbalances may be
present when arrest patients enter the ED, the average iCa value from 12 patients being
0.67 (range 0.26 - 0.89 mmol/L) where the reference range was 1.15 - 1.31 mmol/L.
These patients frequently receive epinephrine and DC voltage therapy in an effort to
restore normal rhythm; therapeutic results from both being cation-(iCa, K, and iMg)
dependent.
• Acute myocardial infarction (AMI)
It is well recognized that the earlier successful thrombolysis occurs, the better the
outcome in patients suffering infarction. Stasis time is frequently equated to quantity of
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cardiac muscle irreversibly damaged. However, the risk of stroke or other hemorrhage
from thrombolytic therapy, ~1-6% of patients,47-49 is weighed against its use. Many
clinicians hesitate to use the muscle- and possibly life-saving therapy when ECG
indication is negative or equivocal. Evidence for a significant rise in myoglobin50-52 to
rule in, or perhaps a low level of lactate to rule out53 AMI may aid in making this
therapeutic decision. Lactate is a prognosticator for cardiogenic shock in these
patients.54 Patients also tend to become more hypomagnesemic and hypokalemic
during the acute phase of infarction.25,55,56
• Occult disease
Rapid lactate determination in the ED is effective at identifying geriatric patients who
are at increased risk for morbidity and mortality and identifies many of those not
requiring acute intervention or admission.57
Operating Room
Large volumes of fluid are frequently introduced into surgical patients resulting in
changes to their plasma matrices. Although a CCP may benefit emergency surgeries, and
sometimes even general surgeries, two examples of surgical patients that are helped are
those receiving cardiopulmonary bypass or transplants.
• Cardiopulmonary bypass (CPB)
Many factors that may contribute to the overall plasma makeup in a CPB patient.
Prior to surgery, blood may be taken from the patient for autologous transfusion, with any
replacement fluid causing hemodilution. Anesthesia may alter the kidney's ability to
manage cation balance [e.g. K58 and iMg]. A cross-clamp denies cardiac myocytes
oxygen, setting them up for loss of iMg, reperfusion injury, and inflammatory response.
Cardioplegia is administered to the patient to reduce myocardial cell expenditure of
energy; i.e., adenosine triphosphate (ATP). The cardioplegia contains a high
concentration of K to induce cardiac arrest. It may also contain iMg, low iCa, cationactivity-dependent drugs, and various cation-binding ligands. The bypass pump requires
a cation-binding anticoagulant to avoid clotting and a prime that includes cation-binding
ligands and that results in hemodilution, particularly for pediatric patients. The attending
clinician may be administering insulin/glucose or calcium salts to control elevated K
levels, citrated blood products (citrate being a calcium and magnesium binder) and drugs
to improve hemodynamic status when the surgery is finished. Natural glucose generation
during bypass could lead to a greater lactatemia during regional ischemia, resulting in
increased tissue damage.5 An awareness of the plasma biochemistry as the cross clamp is
removed could be helpful as the heart is restored to normal rhythm. Post surgery,
hypomagnesemia has been associated with atrial arrhythmias.59-61
• Liver transplant surgery
The natural physiologic responses in CPB also occur in liver transplant surgery. In
addition, large volumes of citrated blood products are used in these patients. Hematocrit
or hemoglobin monitoring is important when these fluids are used. Kost and his
colleagues62 reported how dramatically TCa and iCa differed in these patients, iCa being
greatly depleted by citrate even though TCa was in excess. Citrate-binding likely affects
iMg and iCa similarly. Donor livers, transported in solutions containing various
electrolyte concentrations, buffers and other constituents, introduces K and hydrogen
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ions into their recipients. These changes in the plasma are thought to contribute to
cardiac instabilities over the first twenty minutes or so in the recipient as the donor's liver
is introduced. The value of Mg therapy and lactate monitoring are also being evaluated
for these patients.
Intensive Care Unit
As in the OR, rapidly changing plasma matrices in unstable patients need to be
recognized and understood quickly. A periodic CCP along with emergency intervention
may help to support these patients. Perfusion deficits and electrolyte imbalances
frequently occur in the ICU.
• Shock
Shock has many origins, each resulting in inadequate perfusion to the tissues. Some
clinicians refer to the "golden hour of shock" which may be the amount of time they have
to resuscitate a patient before irreversible shock sets in, leading to death. Early, nonspecific markers for developing shock include a change in cardiac output and a decrease
in mixed venous oxygen saturation, neither of which may detect regional perfusion
deficiencies. A compensatory response in which the baroreceptors, recognizing
inadequate cardiac output, initiate the redirection of blood from the peripheral vasculature
to the more vital organs (heart and brain) provides some indication of developing shock
(e.g. reduced Na in urine, reduced transcutaneous pO2 vs arterial pO2, cooler toe
temperature). Insufficient oxygen to support cellular ATP synthesis, however, provides
one of the earliest reliable markers for developing shock; lactate. Lactate is the only
blood marker whose presence generally means that tissues are receiving inadequate
oxygen. As ATP reserves fail, electrolyte imbalances follow.63-66 If lactate is increased
in a patient; pH, pO2, glucose, hematocrit, and the electrolytes may provide clues to the
reason for its increase. As lactate increases, divalent cation activity may be reduced due
to lactate-binding. Several traditional parameters such as mean arterial pressure, heart
rate, central venous pressure, and cardiac output are poor criteria for monitoring the
circulatory status in critically ill patients.67
In a study of 79 sequential admissions to their ICU, Khastgir et al68 determined that 7
of the patients had unpredicted lactate elevations. They concluded that early intervention
in these patients led to better outcomes. In addition to indicating the need for invasive
hemodynamic monitoring, Abramson et al39 realized that elevated lactate 24 hours
following treatment for trauma suggested missed injury and the need for surgical
intervention. Information from sequential lactate determinations, specifically a decrease
of 5% in 20 minutes and 10% or more in 1 hour, suggested to Vincent et al69 that their
resuscitation strategy was working in their patients experiencing circulatory shock.
• Transfusion
In an era of concern about biotransmittible disease, the unnecessary use of blood
products is discouraged. Oxygen-carrying substitutes on the horizon will likely be very
expensive. To determine the need for oxygen-carriers, clinicians frequently rely on the
hematocrit (or hemoglobin) values and clinical judgment. For example, is a hematocrit
of 30% or perhaps 24% adequate for a given patient? Some institutions set guidelines for
transfusions based on a hematocrit value which may differ from that of a neighboring
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medical center. If a patient with a stable hematocrit of 20% has a normal lactate value, is
there a need for transfusion?
• Burns
Burn resuscitation has traditionally been guided by urine output, mean arterial
pressure, and/or central venous pressure. Jeng et al70 have recently reported that patients
who have been resuscitated to an hourly urine output of 30 ml and a mean arterial
pressure of >70 mm Hg may still have elevated blood lactate and base deficit values.
Patients resuscitated to the urine output and MAP guidelines, who have higher lactate
values, have poorer outcomes. Hemoconcentration as determined by hematocrit could be
a better indicator of volume repletion than urine output or mean arterial blood pressure.71
Additional studies noting electrolyte and glucose values during resuscitation are pending.
• Electrolyte imbalances
A patient recovering from surgery for pancreatic cancer developed cardiac
irregularity. While an arterial sample was being analyzed for blood gases via a criticalcare-profiling instrument, the patient arrested. In addition to the blood gases, the
instrument yielded an K value of 8.0 mmol/L and an iCa value of 0.85 mmol/L (reference
range 1.1 - 1.3). A successful resuscitation was immediately affected by administering a
bolus of calcium.72
In 98 sequential admissions, Broner et al73 determined that the analyte most
frequently abnormal in their pediatric ICU patients was TMg. Interestingly, the
hypermagnesemic patients carried a worse prognosis than those that were
hypomagnesemic. Chernow et al74 reported that 61% of their postoperative ICU patients
were hypomagnesemic (TMg) and that these patients tended to have a higher mortality
and more frequent hypokalemia than similar patients with normomagnesemia. Aglio75
and Fanning59 each pointed to the fact that a high incidence of atrial arrhythmias
following bypass surgery correlated with low magnesium values. Brookes et al61
suggested that iMg was affected more significantly than TMg in post CPB patients. A
study by Salem et al76 suggests that low magnesium values may have other clinical
consequences. They determined that animals with lower TMg values, developed through
controlled dietary insufficiency, were more vulnerable to endotoxin challenge.
How to provide a CCP
All of the presently recognized critical analytes may now be measured in a whole
blood sample. Sample-handling time for clotting and/or centrifugation is no longer
necessary. The results of a CCP are now available from 200 uL of whole blood in less
than 90 seconds via a critical care instrument. The challenge then is to reduce sample
transit time in order to reduce turnaround times. Although it has been reported that the
use of a pneumatic tube system allows a TAT of about 6 minutes77, many clinicians are
relying on testing being provided closer to the patient. Stat TAT from a central lab was
determined to be about 1 hour, from a satellite lab about 30 minutes, and from point-ofcare (POC) analysis, 1-5 minutes.78 This study also indicated significant blood savings
by providing POC analysis. Two other advantages of POC analysis are the minimizing of
sample degradation before analysis (preanalytical error) and queuing of samples in the
critical care unit to accommodate the most seriously ill patient.
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Summary
With the advent of critical care profiling, an appropriate menu of tests is now
available via analysis of ~200 uL of whole blood is less than 90 seconds. Where critical
care profiling and point-of-care testing strategies are used, real-time therapy is becoming
a reality for our sickest patients.
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References
Ellison DA, Forman DT. Transient hyperglycemia during abdominal aortic surgery.
Clin Chem 1990;36:815-7.
Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders. McGrawHill, NY, & London 1984
Mills NL, Beaudet RL, Isom OW, Spencer FC. Hyperglycemia during
cardiopulmonary bypass. Ann Surg 1973;177: 203-5.
Inamura K, Smith M-L, Olsson Y, Siesjoe BK. Pathogenesis of substantia nigra
lesions following hyperglycemic ischemia: Changes in energy metabolites, cerebral
blood flow, and morphology of pars reticulata in a rat model of ischemia. J Cereb
Blood Flow Metabol 1988;8: 375-84.
Sieber FE, Traystman RJ. Special issues: glucose and the brain. Crit Care Med
1992;20: 104-14.
Wessel DL, Adatia I, Thompson JE, Hickey PR. Delivery and monitoring of inhaled
nitric oxide in patients with pulmonary hypertension. Crit Care Med 1994;22: 930-8.
Shoemaker WC, Appel PL, Kram HB, Bishop M, Abraham E. Hemodynamic and
oxygen transport monitoring to titrate therapy in septic shock. New Horizons
1993;1: 145-59.
Wetzel RC. The intensivist's system. Crit Care Med 1993 ;21/9 (Suppl): S341-4.
Wessel DL. Inhaled nitric oxide for the treatment of pulmonary hypertension before
and after cardiopulmonary bypass. Crit Care Med 1993;21/9 (Suppl): S344-5.
Meadow W. Vascular endothelium as a target and effector organ. Crit Care Med
1993;21/9 (Suppl): S345-7.
Ghezzi P, Dinarello CA, Bioanchi M, Rosandich ME, Repine JE, White CW.
Hypoxia increases production of interleukin-1 and tumor necrosis factor by human
mononuclear cells. Cytokine 1991;3: 189-94.
Paty PB, Banda MJ, Hunt TK. Activation of macrophages by l-lactic acid. Surg
Forum 1988;39: 27-8.
Jensen JC, Buresh C, Norton JA. Lactic acidosis increases tumor necrosis factor
secretion and transcription in vitro. J Surg Res 1990;49: 350-53.
Krause GS, White BC, Aust SD, Nayini NR, Kumar K. Brain cell death following
ischemia and reperfusion: A proposed biochemical sequence. Critical Care
Medicine 1988;16/7, 714-26.
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11
15. Siesjo BK. Mechanisms of ischemic brain damage. Critical Care Med 1988;16:
954-63.
16. Schuster HP. Prognostic value of blood lactate in critically ill patients.
Resuscitation 1984;11: 141-6.
17. Toffaletti J, Hammes ME, Gray R, Lineberry B, Abrams B. Lactate measured in
diluted and undiluted whole blood and plasma: comparison of methods and effect of
hematocrit. Clin Chem 1992;38: 2430 -4.
18. McLean FC, Hastings AB. A biological method for the estimation of calcium ion
concentration. J. Biol Chem 1934;107, 337-350.
19. Scheidegger D, Drop LJ, Laver MB. Interaction between vasoactive drugs and
plasma ionized calcium. Intensive Care Med 1977;3: 200-5.
20. Zaloga G, Prielipp R, Dudas L, Royster R, Butterworth J. Calcium impairs
dobutamine's cardiovascular actions. Crit Care Med 1991;April: S52.
21. Rude R, et al. Mechanism of BP regulation by Mg in man. Magnesium 1989;8: 26673.
22. Seelig M. Cardiovascular consequences of magnesium deficiency and loss:
Pathogenesis, prevalence and manifestations--magnesium and chloride loss in
refractory potassium repletion. Am J Cardiology 1989;63: 4G-21G.
23. Woods KL, Fletcher S, Roffe C, Haider Y. Intravenous magnesium sulphate in
suspected AMI: results of the second Leicester Intravenous Magnesium Intervention
Trial (LIMIT-2). Lancet 1992;339: 1553-8.
24. Roden DM. Magnesium treatment of ventricular arrhythmias. Am J Cardiology
1989;63: 43G-46G.
25. Schechter M, Kaplinsky E, Rabinowitz B. The rationale of magnesium
supplementation in acute myocardial infarction. Arch Intern Med 1992;152: 218996.
26. Altura BT, Shirey TL, Young CC, Dell'Orfano K, Altura BM. Characterization and
studies of a new ion selective electrode for free extracellular magnesium ions in
whole blood, plasma and serum. Electrolytes, blood gases, and other critical
analytes: the patient, the measurement, and the government. Eds: D'Orazio, Burritt,
Sena; pub: Omnipress 1992; (Cape Cod Meeting):152-173.
27. Iseri LT. Magnesium-potassium interactions in cardiac arrhythmias. Magnesium in
clinical medicine and therapeutics, pub. by American Society for Magnesium
Research, proceedings from May 2-4 meeting in LaJolla 1991
28. Levine BS, Coburn JW. Magnesium, the mimic/antagonist of calcium. NEJM
1984;310: 1253-5.
29. Salem M, Munoz R, Chernow B. Hypomagnesemia in critical illness: a common
and clinically important problem. Crit Care Clinics 1991;7: 225-52.
30. Elin RJ, Ryschon TW, Rosenstein DL, Rubinow DR, Niemela JE, Balaban RS.
Intracellular ionized magnesium concentration compared with blood total
magnesium parameters in normal subjects. Clin Chem 1994;40: 1094.
31. Quamme GA, Rabkin SW. Cytosolic free magnesium in cardiac myocytes:
identification of a Mg++ influx pathway. Biochemical and Biophys Res Comm
1990;167: 1406-12.
32. Polimeni P, Page E. Magnesium and heart muscle. Circ Res 1973;33: 367-74.
12
12
33. Frankel HL, Rozycki GS, Ochsner MG, McCabe JE, Harviel JD, Jeng JC, Champion
HR. Minimizing admission laboratory testing in trauma patients: use of a
microanalyzer. J. Trauma 1994;37: 728-36.
34. Michaud LJ, Rivara FP, Longstreth WT, Grady MS. Elevated initial blood glucose
levels and poor outcome following severe brain injuries in children. J. Trauma
1991;31: 1356-62.
35. Merguerian PA, Perel A, Wald U, Feinsod M, Cotev S. Persistent nonketotic
hyperglycemia as a grave prognostic sign in head-injured patients. Crit Care Med
1981;9: 838-40.
36. Altura BM, Zhang A, Cheng TP-O, Altura BT. Intracellular free ionized magnesium
concentration (IMg2+) and its regulation in vascular smooth muscle cells (VSMCs)
as probed by digital-imaging microscopy. IVth European Congress on magnesium
1992: 25.
37. Milzman D, Boulanger B, Wiles C, Hinson D. Admission lactate predicts injury
severity and outcome in trauma patients. Crit Care Med 1992;20/4 (Suppl.): S94.
38. Aduen J, Bernstein WK, Khastgir T, Miller J, Kerzner R, Bhatiani A, Lustgarten J,
Bassin AS, Davison L, Chernow B. The use and clinical importance of a substratespecific electrode for rapid determination of blood lactate concentrations. JAMA
1994;272: 1678-85.
39. Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J.
Lactate clearance and survival following injury. J of Trauma 1993;35: 584-91.
40. Scalea TM, Maltz S, Yelon J, Trooskin SZ, Duncan AO, Sclafani SJA.
Resuscitation of multiple trauma and head injury: Role of crystalloid fluids and
inotropes. Crit Care Med 1994;22: 1610-15.
41. Earnest MP, Yarnell PR, Merrill SL, Knapp GL. Long-term survival and neurologic
status after resuscitation from out-of-hospital cardiac arrest. Neurology 1980;30:
1298-1302.
42. Carden DL, Martin GB, Nowak RM, Foreback CC, Tomlanovich MC. Lactic acid as
a predictor of downtime during cardiopulmonary arrest in dogs. Am J Emergency
Med 1985;3: 120-4.
43. Safar P. Resuscitation from clinical death: pathophysiologic limits and therapeutic
potentials. Critical Care Med 1988;16: 923-41.
44. Hoshino T, Maley WR, Bulkley GB, Williams GM. Ablation of free radicalmediated reperfusion injury for the salvage of kidneys taken from non-heartbeating
donors. Transplantation 1988;45/2: 284-9.
45. Bulkley GB. Free radical-mediated reperfusion injury: A selective review. British J
Cancer 1987;55, Suppl VIII: 66-73.
46. Urban P, Scheidegger D, Buchmann B, Barth D. Cardiac Arrest and Blood Ionized
Calcium Levels. Annals of Internal Medicine 1988;109, 110-113.
47. Ayres SM. Initial management of the patient with presumptive myocardial
infarction. Compendium from the 28th annual U.S.C. symposium on critical care
medicine 1990;(Los Vegas, Nev.): 363.
48. Tiefenbrunn AJ, Sobel BE. The impact of coronary thrombolysis on myocardial
infarction. Fibrinolysis 1989;3: 1-15.
13
13
49. Rackow EC. Myocardial ischemia and its acute management. Critical care medicine
symposium 1992;(green handout book): 274-88.
50. Mair DC, Whipkey R, Bruns DE, Savory J. Potential use of the serum myoglobin in
the emergency room. Clin Chem 1993;39: 1148.
51. Gibler WB, Gibler CD, Weinshenker E, et.al. Myoglobin as an early indicator of
acute myocardial infarction. Annals of Emergency Med 1987;16: 351-6.
52. Vaidya HC. Myoglobin as a marker for myocardial infarction and reperfusion.
Handout at AACC roundtable 1991;49N and 59N.
53. Milzman DP, Pressman D, Manning D, Linden J, Howell J, Lill D, Shirey T.
Emergency department use of lactate to evaluate acute chest pain. abstract submitted
to American College of Cardiology 44th Annual Scientific Session 1995.
54. Mavric Z, Zaputovic L, Zagar D, Matana A, Smokvina D. Usefulness of blood
lactate as a predictor of shock development in AMI. Am J Cardiology 1991;67:
565-8.
55. Rasmussen HS, Cintin C, Aurup P, Breum L, McNair P. The effect of intravenus
magnesium therapy on serum and urine levels of potassium, calcium and sodium in
patients with ischemic heart disease, with and without acute myocardial infarction.
Arch Intern Med 1988;148: 1801-5.
56. Salem M, Kasinski N, Dndrei AM Brussel T, Gold MR, Conn A, Chernow B.
Hypomagnesemia is a frequent finding in the Emergency Department in patients with
chest pain. Arch Intern Med 1991;151: 2185-90.
57. Milzman DP, Manning D, Presman D, Lill D, Howell J, Shirey T. Rapid lactate can
impact outcome prediction for geriatric patients in the Emergency Department. Crit
Care Med 1995; 23 (Suppl.): A32.
58. Williams ME, Rosa RM. Hyperkalemia: disorders of internal and external potassium
balance. J Intensive Care Med 1988;3: 52-64.
59. Fanning WJ, Thomas CS, Roach A, Tomichek R, alford WC, Stoney WS.
Prophylaxis of atrial fibrillation with magnesium sulfate after coronary artery bypass
grafting. Ann Thorac Surg 1991;52: 529-33.
60. England MR, Gordon G, Salem M, Chernow B. Magnesium administration and
dysrhythmias after cardiac surgery. JAMA 1992;268: 2395-2402.
61. Brookes CIO, Fry CH. Ionised magnesium and calcium in plasma from healthy
volunteers and patients undergoing cardiopulmonary bypass. Br Heart J 1993;69:
404-8.
62. Kost, Gerald K, Jammal, Mary A, Ward, Richard E, Safwat, Amira M. Monitoring of
ionized calcium during human hepatic transplantation. Am J Clin Path 1986;86, 6170.
63. Speich M, Bousquet B, Nicolas G. Concentration of Mg, Ca, K, and Na in Human
Heart Muscle after AMI. Clin Chem 1980;26, 1662-5.
64. Siesjo BK. Cell damage in the brain: a speculative synthesis. J Cerebral Blood
Flow and Metabolism 1981;1: 155-85.
65. Siesjo BK. Mechanisms of ischemic brain damage. Critical Care Med 1988;16:
954-63.
66. Sidi A, Rush W, Davis RF. Regional Myocardial Metabolism and Electrolyte
Balance During Acute Ishemia in Dogs. J. Cardiothorasic Anesthesia 1988;2, 650-7.
14
14
67. Shoemaker WC. Circulatory mechanisms of shock and their mediators. Critical
Care Med 1987;15: 787-94.
68. Khastgir T, Lustgarten J, Bassin A, Stacey J, Chernow B. Advanteges of bedside
lactate determination--a prospective comparative trial. Crit Care Med 1992;(April):
S36.
69. Vincent J-L, Dufaye P, Berre J, Leeman M, Degaute J-P, Kahn RJ. Serial lactate
determinations during circulatory shock. Crit Care Med 1983;11: 449-51.
70. Jeng JC, Lee K, Jablonski K, Silva C, Jordan MH. Serum lactate and base deficit
suggest inadequate resuscitation of burn patients. (abstract/talk accepted for
American Burn Assn. meeting 1995)
71. Jeng JC, Lee K, Frankel H, Silva CA, Jablonski K, Jordan MH. Hemoconcentration
suggests inadequate resuscitation of burn patients: application of a point of care
laboratory instrument. Crit Care Med 1995; 23(Suppl.): A88.
72. Fleisher M. (personal communication)
73. Broner CW, Stidham GL, Westenkirchner DF, Tolley EA. Hypermagnesemia and
hypocalcemia as predictors of high mortality in critically ill pediatric patients.
Critical Care Medicine 1990;18: 921-8.
74. Chernow B, Bamberger S, Stoiko M, Vadnais M, Mills S, Hoellerich V, Warshaw
AL. Hypomagnesemia in patients in postoperative intensive care. Chest 1989;95:
391-397.
75. Aglio LS, Stanford GG, Maddi R, Boyd JL, Nussbaum S, Chernow B.
Hypomagnesemia is common following cardiac surgery. J Cardiothoracic and
Vascular Anesthesia 1991;5: 201-8.
76. Salem M, Kasinski N, Munoz R, Chernow B. Progressive magnesium deficiency
increases mortality from endotoxin challenge: the protective effects of acute
magnesium replacement therapy. Crit Care Med 1995;23 : 108-18.
77. Winkelman JW, Wybenga DR. Quantification of medical and operational factors
determining central versus satellite laboratory testing of blood gases. Amer J Clin
Path 1994;102: 7-10.
78. Salem M, Chernow B, Burke R, Stacey J, Slogoff M, Sood S. Bedside diagnostic
blood testing: its accuracy, rapidity, and utility in blood conservation. JAMA
1991;266: 382-9.
79. Shirey TL. Critical care profile testing for informed treatment of severely ill patients.
Am J Clin Pathol (Suppliment in October issue) 1995;104: S79-87.
80. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M,
Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in
critically ill patients. N Engl J Med 2001;345: 1359-67.
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