Bedside ABG, electrolytes, lactate and procalcitonin in emergency pediatrics.

Point of care testing, is the term commonly applied to the bedside tests performed in sick patients. Common clinical conditions encountered in pediatric emergency rooms are respiratory, gastro-intestinal, infections and cardiac. Emergencies at most of the places, especially developing countries are overburdened. Availability of tests like arterial blood gas, lactate, electrolytes and procalcitonin, bedside tests or point of care tests can help identify sick patients quickly. Abnormalities like acid-base disturbances and dyselectrolytemias can be dealt with instantly, thus improving the overall prognosis. Lactate levels in emergency give the earliest clue to cardiovascular compromise and poor tissue perfusion. Procalcitonin has recently gained significant importance as an acute phase reactant for early identification of sepsis. Decisions for initiating or withholding antibiotic therapy can also be taken based on procalcitonin levels in emergency. Bedside estimation of serum electrolytes, blood gas analysis and procalcitonin thus facilitate the clinical evaluation and management of critical patients. An extensive literature review of current status of these investigations as point of care tests is appraised here.

Point of Care testing (POCT) is the term used for bedside tests that are usually performed on critically sick patients in intensive care units, emergency rooms, operating rooms, pre-hospital settings and inside transport ambulances. Delay in laboratory results due to delay in transport and analysis of sample can be critical in the management of pediatric patients. The ability to make rapid decisions and initiate appropriate treatment on time may decrease the stay in Emergency Department and therefore the costs. This is particularly important in developing countries where prolonged duration of stay in emergency departments increases financial as well as occupancy burden. To summarize, the main advantages that are making POCT more and more needed today are decreased turnaround time, reduced cost and improved decision making.[123] When applied in emergency units, POCT can be an aide in better bed management too. Amount of blood used is also less in such kind of testing.

Commonly applied tests as POCT in pediatric emergency include bedside dextrose, arterial blood gas analysis that help in detecting O2 and CO2 disturbances, acid base status, electrolytes and hematocrit. Results are available within 2 min and can be done with the help of simple hand held devices. Other tests that can be used as POCT include lactate, inflammatory markers like C-reactive protein and procalcitonin, coagulation studies, Troponin-T, drug profile in cases of suspected abuse specially adolescents, urinary dipstick for sugar, ketones etc., Arterial blood gas analysis, lactate, electrolytes and procalcitonin are frequently used Point of care tests in busy pediatric emergency setting, that can be applied for immediate diagnosis, making admission decision and emergent management and as a result, improve the outcomes.

In order to answer this need, researchers have used various handheld devices at patient's bedside. POCT for serum electrolytes is available from specialized equipment such as iSTAT or STAT Profile Critical Care Xpress analyzers. The portable i-STAT weighs 18 ounces, is a portable handheld analyzer which requires no special sample preparation or user calibration; with minimal maintenance. Each test cartridge contains chemically sensitive biosensors on a silicon chip that are configured to perform specific tests. To perform a test, 2 to 3 drops of blood are applied to a cartridge that is then inserted into i-STAT handheld. Prior to running a test, the cartridge initiates a series of preset quality control diagnostics, from monitoring the quality of the sample to validating the reagent. Test-specific, single-use i-STAT cartridges are available for a range of clinical tests, including cardiac markers, lactate, coagulation, blood gases, chemistries and electrolytes and hematology. Test results are uploaded automatically when i-STAT handheld is placed in a downloader. An evaluation of the performance of i-STAT using a disposable cartridge EG7+, measuring pH, pO2, pCO2 (blood gas), sodium, potassium, ionized calcium and hematocrit with only 10 microliters of heparinized blood was done by Pidetcha et al. The authors concluded that the results obtained from iStat were comparable to the routine laboratory results in terms of accuracy and precision accurate.[4]

O’Shaughnessy et al., determined the accuracy of POCT quality control testing of an ED maintained ABG Analyzer. The authors compared comprehensive quality control data obtained when the ABG analyzer was maintained by the Department of Clinical Laboratories with data obtained from the same analyzer when it was maintained by ED attending physicians and reported that ED physicians were capable of maintaining a quality control as a POCT device under the parameters set by the College of American Pathologists.[5]

There are studies that have compared i-STAT portable clinical analyzer with blood gas analyzer in neonatal intensive care unit. Results of serum electrolytes from i-STAT correlated well with the blood gas analyzer for sodium and potassium with the exception of ionic calcium. Another important role of these POCT analyzers in this vulnerable group of population is prevention of iatrogenic anemia by minimizing the blood loss. Implementation of a bedside multi-parameter POCT analyzer in Neonatal intensive care unit (NICU) thus, decreases transfusions among neonates particularly among the low birth weight babies by reducing iatrogenic blood loss for central laboratory testing.[6]

Hsiao et al., compared the effect of point-of-care testing versus traditional laboratory methods on length of stay in a pediatric emergency department (ED). They concluded that Point-of-care tests significantly reduced the duration of stay in emergency room, thus facilitating patient flow in busy pediatric emergencies.[7]

Arterial blood gas

Arterial blood gas analysis (ABG) is an important investigation for every pediatric emergency physician. Serious acid base disturbances can co-exist without significant clinical manifestations in various pathologies involving respiratory, cardiovascular, gastro-intestinal, renal and endocrine organ systems. ABG analysis tells us about tissues oxygenation status, adequacy of ventilation and acid-base status disturbances. The parameters it measures are pH, partial pressures of carbon dioxide and oxygen and bicarbonate level in the blood. Hematocrit, electrolytes, including sodium, potassium and ionized calcium, lactate, oxyhemoglobin, carboxyhemoglobin and methemoglobin levels can also be measured by these machines within minutes.

Oxygenation and ventilation are important factors in the treatment of emergency patients. A number of studies have shown that the severity of hypoxemia is frequently underestimated, even by experienced emergency physicians. With noninvasive methods such as pulse oximetry and capnometry, the ability to obtain reliable measurements assessing oxygenation and ventilation can be limited by abnormal physiologic states commonly seen in emergency patients. In emergency conditions, ventilation/perfusion (V/Q) mismatch affects end tidal CO2 (EtCO2) measurements. Also, feeble pulse signal results in the failure of pulse oximetry to measure arterial hemoglobin saturation (SpO2). Prause et al., used a portable, battery-powered blood analyzer on patients in life threatening conditions to determine pH, pCO2, pO2, sodium, potassium and ionized calcium and concluded that knowledge of the patients’ pH, pCO2 and pO2 yields more objective information about oxygenation, carbon dioxide and acid-base regulation than pulse oximetry and/or capnometry alone. Additionally, it enables physicians to correct severe hypokalemia or hypocalcemia in cases of cardiac failure or malignant arrhythmia.[8] Thus, ABG as a point of care test plays a significant role in detecting impending respiratory failure and need for oxygen therapy and ventilator care. It also helps in detecting the serious abnormalities in the emergency room itself, so that normal homeostasis can be resumed and the organ function recovers fast.

Hypoxia, the initial abnormality in respiratory diseases can be detected at the bedside by ABG analysis. Although Burri et al., demonstrated that ABG failed to differentiate between pulmonary and non-pulmonary causes of acute dyspnea in ED,[9] it was highly predictive of intensive care unit admission and mortality, thus remaining an important point of care investigation. Camargo et al., studied the role of ABG managing asthma exacerbations in the Emergency Department and concluded that though ABG analysis tells us about oxygenation status in asthma; it did not affect management of asthma exacerbations.[10] Respiratory alkalosis and acidosis can also be detected by bedside ABG analysis thus, helps in deciding further management strategies.

Severe metabolic abnormalities like metabolic acidosis and alkalosis are often seen in emergency setting. In severe acidosis, i.e. pH <7.20, poor myocardial performance, arrhythmias, hypotension, pulmonary edema and hyperkalemia are likely to occur. Similarly, in severe alkalosis, i.e. pH >7.5, features like mental confusion, muscular irritability, seizures, arrhythmias, generalized tissue hypoxia and hypokalemia occur.[11] Identification of these clinical features that overlap with manifestations of the primary disease itself in a sick child, becomes difficult, making ABG analysis an important point of care investigation in this setting. Acute gastroenteritis (AGE) is a common condition seen in pediatric emergencies, both in developing as well as developed countries. Madati et al., performed ABG in 130 patients of AGE and observed that dry mucous membranes and duration of illness of more than 2 days were good predictors of acidosis (sensitivity 90%). Early identification of acidosis thus allow emergency physician to focus on more aggressive rehydration.[12] Metabolic acidosis is also reported as a promising tool for early detection of gastrointestinal syndromes.[13] Hyponatremia (56%), hypokalemia (46%) and metabolic acidosis (94%) were reported as common abnormalities in a study from Nepal in patients with diarrhea and dehydration. These abnormalities were found to be significantly high in patients who died during the course of illness,[14] thus giving a clue about the overall prognosis.

ABG can also be helpful in detecting psychogenic hyperventilation at the bedside itself, thus obviating the need for unnecessary extensive investigative workup. ter Avest et al., demonstrated hypocapnia and alkalosis in presence of high lactates in psychogenic hyperventilation.[15]

Lactate

Lactate levels can serve as one of the earliest markers of damage that has been caused at tissue level. Lactate accumulates as a result of anaerobic metabolism at tissue level in presence of inadequate oxygen delivery. Common conditions leading to lactic acidosis in ER are hypoxemia due to any reason, severe anemia or shock. When the underlying cause of lactic acidosis is alleviated, the liver is able to metabolize the accumulated lactate into bicarbonate, correcting the metabolic acidosis. In children with severe liver dysfunction, impairment in lactate metabolism may also lead to lactic acidosis.

Higher lactate levels in pre hospital setting in pediatric patients with shock were found to be associated with increased duration of intensive care unit stay and mortality.[16] Shinozaki et al., also reported high levels of lactate (>12mmol/l) and ammonia (>170mcg/dl) independently as prognostic factors in patients with out-of- hospital cardiac arrest.[17] Palaino et al., in their interesting work added lactate and base deficit to traditional vital signs in patients with trauma. Lactate levels are considered to be an indirect marker of hemorrhage as bleeding leads to decreased tissue perfusion. They found that adding these metabolic parameters identified major injuries with a sensitivity of 76.4% than vital signs alone that were able to recognize major injuries with 40.9% sensitivity.[18] Identification of shock in early stages may be at the stage of Systemic Inflammatory Response Syndrome (SIRS) being able to help to prevent the irreparable damage to the vital organs. Scott et al., hypothesized that early hyperlactatemia (serum lactate ≥4.0mmol/L) would be associated with increased risk of organ dysfunction among children with SIRS. They observed that increased lactate was associated with increased risk of organ dysfunction, resuscitative therapies and critical illness.[19] Mtove G did POC measurement of blood lactate and glucose in children between the ages of 2 months and 13 years with a history of fever. The authors demonstrated that POC lactate measurement can contribute to the assessment of children admitted to hospital with febrile illness and can also create an opportunity for more hospitals in resource-poor settings to participate in clinical trials of interventions to reduce mortality associated with hyperlactatemia.[20]

Thus, measurement of lactate as point of care test can certainly help not only in predicting the overall prognosis in pre-hospital and emergency setting, but also planning interventions to reduce morbidity and mortality.

Electrolytes

Dyselectrolytemias greatly affect myocardium, central nervous system, muscle and gastrointestinal tract. Prompt identification and management of electrolyte abnormalities decreases morbidity and mortality. This requires rapid and accurate assessment of serum electrolyte levels in order to initiate appropriate treatment as early as possible. For the future period to get results from central laboratories ranges from 15 min to hours that could unfavorably impact outcomes.[21] ABG analyzer, used as a point of care test gives results faster than the central laboratory autoanalyzers, thereby gaining importance as Point-of-care testing (POCT) of electrolytes in the emergency department (ED), where rapid diagnosis and management can significantly alter the outcome. It enables us to take decisions rapidly but there are concerns related to its reliability, test validity and operational cost, a major deterrent of its use in developing countries. There are studies which have compared the reliability of electrolyte values obtained by ABG as compared to autoanalyzers. Chhapola et al., reported that ABG analyzers underestimated both sodium and potassium values in pediatric intensive care unit patients, in statistically significant terms.[22] Similar, conclusions were made by Morimatsu et al., for sodium and chloride values in They have concluded that the result from two different technologies differ significantly for sodium, potassium and chloride concentration.[23] They have attributed the difference to liquid sodium heparin which was used during sample collection.

Prichard JS evaluated ABL-77 as point of care analyzer for measuring blood gases, electrolytes and hematocrit and reported it to be a reliable tool in cardiovascular operating rooms.[24] Similarly, potassium values were found to be reliable in an Indian study on ICU patients, but not sodium.[25] Similar results were obtained by Chacko et al.[26] The authors compared the value of electrolytes obtained from central laboratory and from point of care blood analyzer. There was a significant difference in the mean sodium value between whole blood and serum samples. Potassium levels were similar in both methods of testing. Whereas another study conducted in Croatia found no difference in the electrolyte values obtained from Stat Profile Critical Care Xpress multiprofile point-of-care analyzer and standard laboratory methods.[27]

POCT can also be useful while we are transporting the patient to health facility. Rapidity of results can help us to save the patient while on the way to hospital. This is particularly important for serum electrolytes like potassium, calcium. Dyselectrolytemia can precipitate arrhythmias which can be fatal and if cared for during the transport it can be a life saving measure. The usefulness of POCT for measurement of electrolytes was evaluated by Prause et al. and they concluded that the system was very useful and reliable and could be an important part of a transport emergency system.[8]

Procalcitonin

Inflammation is a core problem in pediatric medicine. Rapid and reliable diagnosis of inflammation, whether viral or bacterial, is essential for appropriate treatment. Rapid diagnosis is critical because uncontrolled infections may lead to sepsis with a high mortality rate. Current markers of inflammation are leukocyte count and leukocyte differentiation, C-reactive protein (CRP), procalcitonin (PCT) and interleukins (IL)-6 and 8. PCT has emerged as an early and reliable inflammatory marker. The advantages of PCT over older markers are the specificity for bacterial infection (verses inflammation in general), the rapidity of its rise after an insult (6 h), the rapid decline with immune control on infection (half-life of 24 h), excellent correlation with severity of illness (higher levels in more severely ill) and the lack of impact of anti-inflammatory and immunosuppressive states on production.

Procalcitonin (PCT), a peptide precursor of hormone calcitonin comprising 116 amino acid residues with molecular weight of about 13 kDa is produced by C cells of thyroid gland. PCT production during inflammation is from neuroendocrine cells of lungs and intestine. Its production during inflammation is linked with bacterial endotoxin and inflammatory cytokines.[28] PCT is encoded by CALC-1 gene located on chromosome 11. PCT is devoid of any hormonal activity and it is after intracellular cleavage by proteolytic enzymes that active hormone is generated. Serum PCT has a half-life of 25 to 30 h. In normal patients the circulating value is less than <0.10ng/ml well below detection level of standard laboratory test.[29] Blood levels of PCT may raise up to 100μg/L in presence of systemic infections.

It was in 1993, when Assicot et al., first performed procalcitonin levels in children to differentiate bacterial from viral meningitis that its role as a marker of sepsis.[30] Since then, numerous studies were conducted to evaluate its role as a marker of sepsis. A multicentre study compared procalcitonin with C reactive protein (CRP) for the early diagnosis of invasive bacterial infections in febrile infants and found that PCT offers better specificity than CRP for differentiating between the viral and bacterial etiology of the fever with similar sensitivity and can detect invasive infections if the evolution of the fever is <12 h.[31] Another study compared PCT with CRP and neutrophil count and reported that high PCT levels correlated with bad prognosis, particularly in presence of MODS or shock. The measurement of PCT gives information about the severity of bacterial infection in all pediatric ages.[32] Neonatal sepsis is an important cause of neonatal morbidity. Studies have confirmed the superiority of PCT over CRP in identifying both early and late onset sepsis.[3334] Recently role of PCT to initiate or discontinue antibiotics in acute respiratory tract infections was studied.[35] This systematic review included 14 randomized control trials on adult patients on a wide spectrum of acute respiratory diseases. The authors concluded that use of procalcitonin to guide antibiotic therapy was not associated with higher mortality rates or treatment failure. This conclusion is especially useful in countries where antibiotic use is rampant. Procalcitonin has also been used in identification of at risk febrile young infants as a marker of bacterial infection in sequential systematic approach.[36]

PCT can be detected by standard laboratory techniques which require 4-6 h to provide test result. Recently new automated rapid quantitative assay, the VIDAS B·R·A·H·M·S PCT assay (bioMe@rieux, Lyon, France) and BRAHMS PCT-Q (B·R·A·H·M·S Aktiengesellschaft, Hennigsdorf, Germany), has been developed which are fully adapted for emergency conditions.[37]

VIDAS B·R·A·H·M·S PCT assay is based on an enzyme-linked fluorescent immunoassay (ELFA) and with a functional sensitivity of 0.09 ng/mL as per the manufactures. PCT-Q® (Brahms, Germany) is a semi-quantitative rapid immunochromatographic test that uses lateral-flow immunochromatography to measure procalcitonin. The test requires 200 μL of serum/plasma obtained from venepuncture and a 30-minute incubation period to complete. At PCT concentrations of ≥0.5 ng/mL, a reddish band forms, the colour intensity directly proportional to the PCT concentration. The test is read with a reference card, which allows the patient's PCT level to be classified into one of four semi-quantitative categories (<0.5 ng/ml, 0.5 to 2 ng/ml, 2 to 10 ng/ml and >10 ng/ml). In clinical practice, PCT values appear to be available within one hour of venepuncture. Analytical performance of the VIDAS (R) BRAHMS PCT assay was assessed and also compared with the semi-quantitative PCT-Q test (BRAHMS Aktiengesellschaft, Germany) at Dong-A University Medical Center.[38] The authors conclude that, compared with CRP, the measurement of PCT using the new ELFA is a better diagnostic biomarker of sepsis.

Procalcitonin is one of the biomarkers that have the potential to be effectively used as a point of care test in emergency conditions, for identification of bacterial infections thus, to decide about antibiotic initiation and continuation.

CONCLUSION

Arrival of new technologies in microprocessors and microcomputers has shifted the laboratory to patient's bedside. There has been evolution of technology from the simple observation of samples (eg, clarity, color and odor) and comparing colour changes in reagent strips to sophisticated, automated, portable cost effective instruments called the point of care analyzers. Advantages of POCT over conventional laboratory measures are decreased reporting time which helps in early decision making and rapid response to critical values of electrolytes, lactate and blood gas. Besides, procalcitonin, a biomarker of inflammation is rapidly proving itself useful as a point of care investigation than CRP. The results are obtained in minutes and helps clinicians to initiate or withdraw antibiotic treatment. It aid in shortening the duration of stay in emergency department, by helping emergency physicians make quick decisions, thus, being convenient for both patients and physicians. The instrument used for POCT is portable, light and user-friendly. Small blood samples required to perform the test is another valuable asset for neonatal and pediatric patients, in the emergency areas.