In right setting, POC testing
  can be kid stuff

March 2005
Feature Story

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 costs.

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," he said.

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 explained.

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 complete."

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," he said.

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.