Since laboratory test results are only part of the information clinicians
use to diagnose and treat disease, demonstrating a direct relationship
between laboratory testing and improved patient outcomes has been a challenge
for laboratory researchers. Equally difficult is proving that point-of-care
testing is more efficacious and cost-effective than traditional laboratory
testing in certain circumstances. But emerging data suggest that when
caring for the sickest neonatal and pediatric populations, POC testing
can have a profound impact on patient outcomes, and potentially reduce
During a Jan. 19 audioconference titled, "Neonatal and Pediatric Point-of-Care
Testing: Opportunities and Outcomes," sponsored by the i-Stat Division
of Abbott Diagnostics and presented by the American Association for Clinical
Chemistry/National Academy of Clinical Biochemistry, researchers discussed
the promise of POC testing in neonatal and pediatric populations. For
these patients, POC testing "has great potential, mainly because it requires
less blood than traditional laboratory testing, and can there fore be
helpful in reducing blood loss and the need for transfusions," said James
Nichols, PhD, associate professor of pathology at Tufts University School
of Medicine, director of clinical chemistry at Baystate Health System
in Springfield, Mass., and moderator of the audioconference.
In addition, said Michael Bennett, PhD, FRCPath, professor of pathology
at the University of Pennsylvania School of Medicine and director of the
metabolic disease laboratory at Children’s Hospital, Philadelphia, the
use of POC testing in pediatric populations can be quite practical, since
multiple laboratory measurements—sometimes even in rapid succession—are
often necessary in diagnosing, treating, and managing sick neonates. "We
also need to do more frequent repeat analyses in this population, due
to the unique physiological demands of the newborn infant," he said.
Anthony Rossi, MD, director of the cardiac intensive care unit at Miami
Children’s Hospital Congenital Heart Institute in Florida, is all too
familiar with the physiological needs of sick babies, particularly those
with congenital heart defects. At Miami Children’s Hospital, Dr. Rossi
runs a 16-bed unit that’s dedicated to caring for children with congenital
heart disease. "The majority of patients admitted to this unit are candidates
for congenital heart surgery," and POC testing has become an essential
part of caring for them, Dr. Rossi said.
Convinced there was a way to improve the outcomes in neonatal and pediatric
cardiac surgery patients, Dr. Rossi and his colleagues decided to look
for a principle that they could apply universally to their patient population.
"What we realized is that oxygen delivery and monitoring oxygen delivery
were crucial in managing patients with any type of critical illness,"
he said. "From a review of the literature, we found that if you could
achieve a normal oxygen delivery, or even better a supernormal oxygen
delivery, mortality would be less, end organ damage would decrease, morbidity
would decrease, and hospital stays would be shorter."
The average person, Dr. Rossi noted, delivers about five times as much
oxygen as he or she consumes, but when this ratio becomes 2:1, he or she
begins to reach what Dr. Rossi calls the critical point of oxygen delivery.
"At that critical point of oxygen delivery, as we continue to diminish
oxygen delivery, oxygen consumption decreases," he said. "At a certain
point, oxygen consumption will be dependent on oxygen delivery, and that’s
where anaerobic metabolism begins." When patients reach this critical
point, further decreases in oxygen delivery place them at greater risk
of complications and mortality.
The solution, then, Dr. Rossi concluded, was to prevent patients from
reaching a point where oxygen deficits were putting them in peril. But
the problem was finding an objective, direct measure of oxygen delivery
that could be used in neonates and pediatric patients undergoing congenital
heart surgery. "Many such indicators are affected by our medical therapies,
so what we’re seeing in a patient we’re evaluating in terms of hemodynamic
measures often isn’t really an indicator of their true hemodynamic status,"
Dr. Rossi explained.
He and his colleagues began to explore biological indicators of oxygen
saturation, and this research led to an examination of pH and blood lactate
levels as the two indicators related to patient outcome in neonatal and
pediatric congenital heart surgery patients. "What we discovered is that
a number of postoperative patients have elevated blood lactate levels,
while their arterial pH level is in the normal range," Dr. Rossi said.
Arterial pH was probably being affected by medical therapies they were
using, he added, and therefore it could not be depended on to predict
when lactate levels were becoming elevated. "The presence or absence of
elevated lactate couldn’t be assumed by indirect measures of oxygen delivery,
so we had to measure lactate directly," he said.
Dr. Rossi and his colleagues also discovered that elevated lactate levels
on admission were associated with a higher risk of mortality, and low
lactate levels were associated with a lower mortality risk. "We found
that if your lactate level was not elevated or was less than 5 mmol/L
on admission, you had very low mortality, but only about one-third of
our patients with peak lactates greater than 20 mmol/L survived," he said.
Patients who had a lactate of 10 mmol/L or higher on admission had a much
greater chance of dying than patients with lower lactate levels around
6 or 7 mmol/L. "What was really interesting, however, was that patients
whose lactate levels peaked at three hours had a much better chance of
survival than those patients whose lactate levels peaked at eight hours,"
After examining their data, Dr. Rossi and his colleagues concluded that
serum lactate trends following cardiac surgery are reliable predictors
of mortality, and therefore it’s important to control lactate levels in
this population. In the cardiac ICU at Miami Children’s, Dr. Rossi decided
to use lactate levels as a target goal for medical management. In 2001,
he and his colleagues embarked on a study to determine the impact this
particular goal-directed therapy would have on the outcomes of patients
in the cardiac ICU. The study’s findings were published recently in Intensive
Care Medicine (2005; 31: 98-104).
"For this study, we measured serial lactate on all of our patients after
surgery, performing the lactate tests at the point of care whenever we
did our blood gases, which was usually about every four hours for most
patients having heart surgery, and every hour for the first four hours
in neonates having heart surgery," Dr. Rossi said. To factor the risk
of surgery into the study, the RACHS-1 scoring system was used. This system
"assigns a risk of one to six for all of the surgeries that are routinely
performed, with one being the lowest-risk surgeries and six being the
highest-risk surgeries," Dr. Rossi explained.
A total of 710 patients undergoing surgery from July 2001 through September
2003 were compared with a cohort of 1,656 patients who had surgery from
June 1995 through June 2001. In July 2001, Miami Children’s cardiac ICU
began to perform blood lactate measurements serially for 24 hours after
heart surgery, amending therapy based on lactate values and trends. "With
goal-directed therapy, we had a decrease in mortality that was statistically
significant," Dr. Rossi said. In surgeries with a RACHS-1 score of three
or four, there was also a statistically significant decrease in mortality,
and in surgeries with a RACHS-1 score of five or six, there was a marked
decrease in mortality.
"For all patients, we had a marked reduction in mortality from 4.7 percent
pre-goal-directed therapy to 1.6 percent post-goal directed therapy. In
addition, postoperative stay has been diminished by almost one-third since
we started our goal-directed point-of-care algorithm," Dr. Rossi observed.
Why was POC testing essential in instituting goal-directed therapy based
on lactate levels? First, as Drs. Nichols and Bennett said, it was important
to draw as little blood as possible from these infants, particularly since
they had already had surgery. "In preterm babies, up to 10 percent of
their total blood volume can be extracted from a single 10-mL blood draw,
and only when the infant reaches two years of age is a 10-mL blood draw
actually only one percent of the child’s total blood volume," Dr. Bennett
Second, rapid test turnaround times were an imperative part of the protocol,
and they were possible in Dr. Rossi’s hospital only with POC testing instruments.
"In patients who’ve had congenital heart surgery, an increase in CO2
or PCO2 in the blood can lead to a rapid
demise in clinical status, so quick turnaround times are important," he
said. "We wanted to give the clinicians the ability to react quickly to
changing physiologic conditions."
With POC testing, Dr. Bennett said, a large number of analytes can be
measured simultaneously on less than 100 µL of whole blood, which
is important in neonatal and pediatric patient populations. "When that
100 µL of whole blood comes from a newborn, it’s a very precious
commodity," he said.
Using POC testing to improve outcomes is being explored in other neonatal
and pediatric settings. "In the pediatric world," Dr. Bennett said, "we
don’t know whether a child is coming in with diabetes unless they have
been previously diagnosed, so we have to differentiate this clinical presentation
from other endocrine causes of elevated blood glucose. Now, it’s possible
to do this, because there are point-of-care devices in the emergency room
that can measure glycated hemoglobin, glucose, and other analytes using
only 5 µL of blood in a process that takes about six minutes to
Although his laboratory does not yet have hard data, Dr. Bennett said
caregivers in his lab believe that diabetic ketoacidosis children stabilize
much more rapidly in the emergency room when point-of-care devices are
used to monitor their status. "Our caregivers also believe that the use
of POC testing in this patient population leads to less time in ICU admissions,
and to earlier patient discharge," Dr. Bennett said.
Drs. Bennett and Nichols caution, however, that some POC testing technologies
have limitations. For example, Dr. Bennett said, most point-of-care glucose
testing devices weren’t designed for monitoring hypoglycemia. "We’ve set
a rule that any glucose level below 40 mg/dL should be confirmed by the
lab. In addition, most point-of-care glucose analyzers are inaccurate
at levels greater than 400 mg/dL, but in our hands, in patients with diabetic
ketoacidosis, where there are real issues related to hemoconcentration,
for instance, we’re not looking at the matrix in which most of the evaluations
of these devices were actually made," he said.
Matching the device to the clinical need of the patient is important,
said Dr. Nichols, who described that as the take-home message. "We need
to balance benefits with risks, and take into account the limitations
of the methodology, the accuracy of the methods we’re using, and the need
of the patient in terms of making a decision."
Dr. Rossi said what he and his colleagues have learned about the relationship
between lactate levels, POC testing, and patient outcomes could eventually
reach well beyond neonatal and pediatric congenital heart surgery patients.
In their view, the goal-directed, point-of-care combination has applications
in many high-risk patient populations, "and needs to be studied further,"
Sue Parham is a writer in Edgewater, Md. Dr. Nichols encourages those
who want to learn more about the use of POC testing in pediatric populations
to read the NACB’s draft laboratory management practice guideline on POC
testing, which can be found on the NACB Web site at www.nacb.org.