|Year : 2020 | Volume
| Issue : 3 | Page : 104-108
Correlation of red cell distribution width and serum lactate levels in critically ill pediatric patients
Ni Made Sukewanti1, I Nyoman Budi Hartawan1, Dyah Kanya Wati1, Ida Bagus Gede Suparyatha1, Christopher Ryalino2
1 Department of Child Health, Udayana University, Denpasar, Bali, Indonesia
2 Department of Anesthesiology and Intensive Care, Udayana University, Denpasar, Bali, Indonesia
|Date of Submission||19-Mar-2020|
|Date of Decision||28-Apr-2020|
|Date of Acceptance||12-May-2020|
|Date of Web Publication||18-Jul-2020|
Dr. I Nyoman Budi Hartawan
Department of Child Health, Udayana University, JL, PB Sudirman, Denpasar 80232, Bali
Source of Support: None, Conflict of Interest: None
Background: Blood lactate concentration has been widely used as a marker of altered tissue perfusion. An increase in lactate concentration to >1.5 mEq/L is associated with a higher mortality rate. Red cell distribution width (RDW) measures variability in red blood cell size. The purpose of this research is to see the correlation between lactate levels and RDW. Patients and Methods: We performed a cross-sectional study to assess the correlation between blood lactate concentration and RDW in critically ill children admitted to the pediatric intensive care unit (PICU) from October 2018 until February 2019. Blood lactate and RDW were taken during the first 24 h of admission. Data were obtained from the medical report. The association between RDW and lactate was determined using Spearman's correlation test. Results: There were forty patients enrolled in this study with a median age of 27 months (ranged from 2 months to 17 years), with an equal proportion of male and female. The median PICU length of stay was 7.5 days, with a mortality rate of 42.5%. The most common underlying disease was pneumonia (35%), followed by sepsis (17.5%) and meningitis (10%). The median lactate level was significantly higher in the nonsurvivor group compared to the survivor group (P = 0.002). The median RDW was also higher in the nonsurvivor group (P = 0.001). There is a moderate correlation between RDW and lactate (r = 0.532, P < 0.001). Conclusion: There was a moderate and significant correlation between RDW and serum lactate level in critically ill pediatric patients.
Keywords: lactate, pediatric, red cell distribution width
|How to cite this article:|
Sukewanti NM, Budi Hartawan I N, Wati DK, Gede Suparyatha IB, Ryalino C. Correlation of red cell distribution width and serum lactate levels in critically ill pediatric patients. Bali J Anaesthesiol 2020;4:104-8
|How to cite this URL:|
Sukewanti NM, Budi Hartawan I N, Wati DK, Gede Suparyatha IB, Ryalino C. Correlation of red cell distribution width and serum lactate levels in critically ill pediatric patients. Bali J Anaesthesiol [serial online] 2020 [cited 2020 Sep 30];4:104-8. Available from: http://www.bjoaonline.com/text.asp?2020/4/3/104/290091
| Introduction|| |
Since the early studies by Broder and Weil in 1964, blood lactate concentration has been used widely as a marker of altered tissue perfusion in critically ill patients. Lactate level as a clinical prognostic tool was first suggested when they observed that a lactate excess of >4 mmol/L was associated with poor outcomes in patients with undifferentiated shock. Normally, about 1500 mmol of lactate is produced daily from various organs, such as muscle, intestine, red blood cell (RBC), brain, and skin. Lactate is metabolized by the liver (60%), kidneys (30%), and other organs. The normal blood lactate concentration is around 1 mEq/L. Even a minor increase in the lactate concentration to >1.5 mEq/L is associated with a higher mortality rate.,
Numerous works of literature have been published about the importance of lactate concentration in critically ill patients. A systematic review conducted in 2016 consists of 96 studies that evaluated the capacity of serial blood lactate concentration to predict the outcome. Those 96 studies consisting of 14 studies in general intensive care unit (ICU) population, 5 studies in general surgical ICU, 5 in postcardiac surgeries, 14 in trauma patients, 39 in patients with sepsis, 4 in cardiogenic shock, 8 in patients after cardiac arrest, 3 in respiratory failure, and 4 in other conditions. A decrease in lactate levels over time was consistently associated with lower mortality rates in all subgroups.
Hyperlactatemia on admission is known to be a risk factor of mortality among critically ill patients. A study reported that in 1109 children admitted, 115 (10.4%) died in the hospital. The median (interquartile range) blood lactate level in critically ill children was 3.2 mmol/L (2.2–4.8 mEq/L). Among the children, 77.5% had a lactate concentration >2.0 mmol/L. The blood lactate level on admission was significantly associated with mortality. Nevertheless of its usefulness in predicting mortality, blood lactate examination is quite expensive and not available in all countries, especially developing countries.
Red cell distribution width (RDW) measures the variability in the RBC size and is a simple, low-cost, and widely available measure routinely reported as part of a complete blood count (CBC). Several recent studies suggest that RDW may also be useful as a biomarker of disease severity and clinical outcomes in critically ill patients. An increased RDW is an independent predictor of all-cause mortality in sepsis, congestive heart failure, and adult critical illness. Any disease involving RBC destruction or production can increase the variability in the RBC size and lead to RDW elevation.
In critical illness, the acute systemic inflammatory response resulting from various underlying etiologies can alter both erythropoiesis and erythrocyte maturation. The resulting acute rise in RDW may, therefore, reflect the degree of the underlying inflammatory state and provide useful prognostic information and risk of mortality. A retrospective observational study conducted in Chicago had RDW measured from 596 patients on the 1st day of pediatric ICU (PICU) admission. RDW was independently associated with PICU mortality (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.09–1.43). RDW <13.4% (upper limit of lower quartile) had 53% risk of length of stay (LOS) >48 h and 3.3% risk of mortality compared to patients with an RDW >15.7% (lower limit of upper quartile) who had 78% risk of LOS >48 h and 12.9% risk of mortality (P < 0.001 for both outcomes).
A similar study was conducted in Indonesia in 2013–2014 in forty pediatric sepsis patients admitted to the PICU. Using 14.5% as the cutoff point of RDW, they found that the mortality rate in group with increased RDW was 45% compared to 40% in group with normal RDW. There was no significant association between RDW and mortality (P = 0.749).
The increase of blood lactate concentration and RDW both indicates worse prognosis in critically ill patients. While lactate is expensive and not widely available, RDW is a simple marker that routinely evaluated in a CBC. There are still limited data about the correlation between lactate and RDW. A study in Turkey aimed to investigate the prognostic value of lactate and RDW in the critical care unit. A total of 147 patients enrolled in this study. A correlation was observed between the lactate value at 48 h and the mean RDW value at 48 h and mean RDW value during the hospital stay (P = 0.003 and P = 0.005, respectively). Such a correlation would be helpful in limited settings, especially in developing countries where lactate tools might not available. RDW value can be used as a prognostic marker in critically ill children to predict mortality since early recognition of patient at risk of poor prognosis would be helpful in providing timely management and treatment to improve outcome and to identify individuals who warrant early follow-up and intervention.
The purpose of this research is to see the correlation between lactate levels and RDW in critically ill children. Hopefully, this study can be a reference to use RDW as a prognostic marker for critically ill children treated in PICU, especially in limited setting hospitals. Research like this has never been done in Indonesia. This research is considered necessary in Indonesia because of the limited availability of blood lactate test.
| Patients and Methods|| |
This is a cross-sectional study to assess the correlation between blood lactate concentration and RDW in critically ill children admitted to the PICU from October 2018 until February 2019. Inclusion criteria were all patients aged 1 month to 18 years treated in the PICU. Exclusion criteria are children with hematologic diseases such as thalassemia, leukemia, hemolytic anemia, sickle cell anemia, aplastic anemia, and myelodysplastic syndrome and patients with acute bleeding. Informed consent was signed by the parents of the patient or their respective legal guardian. This study has been approved by the Research Ethics Committee of Sanglah General Hospital.
Characteristic data, including age, sex, underlying disease, body weight, height, nutritional status; clinical conditions such as shock, acute respiratory distress syndrome (ARDS), use of mechanical ventilation, PICU LOS, and outcome; as well as laboratory data (CBC, blood gas analysis, and lactate) were obtained. Laboratory data were taken during the first 24 h of admission. Blood lactate concentration (mmol/l) was measured using Accutrend® Plus Meter (Roche Diagnostic, Indianapolis, USA) by taking approximately 0.1 ml of blood using a fingertip needle stick. RDW was part of CBC presented as percentage.
Data were analyzed with Statistical Package for Social Sciences (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. The Chi-square test was used for categorical data. The Student's t- test was used for parametric data, and the Mann–Whitney U-test was used for comparing nonparametric data that were not compatible with a normal distribution. The Spearman correlation analysis was used to assess whether a linear correlation existed between some parameters. Correlation coefficient (r) can be categorized into r = 0–0.19 (very weak), 0.2–0.39 (weak), 0.4–0.59 (moderate), 0.6–0.79 (strong), and 0.8–1 (very strong correlation). A P < 0.05 was considered statistically significant.
| Results|| |
There were 68 patients who met the inclusion and exclusion criteria during our study. Of the 68 patients, forty patients had RDW and lactate measured within 24 h of PICU admission and were included in analysis. The median age of the patients was 27 months (ranges from 2 months to 17 years), with an equal proportion of male and female. Baseline characteristics of the study population are presented in [Table 1].
The most common underlying disease of the patients was pneumonia (35%), followed by sepsis (17.5%) and meningitis (10%). ARDS accounts for 21 (52.5%) of the patients; among them, 17 were using ventilators. Oxygen partial pressure (PaO2)/FiO2 fraction (P/F ratio) was calculated for every patient, ranging from 72 to 562, with a mean P/F ratio of 269. The median PICU LOS was 7.5 days with a mortality rate of 42.5%. The comparison of patient based on mortality is presented in [Table 2].
ARDS was more frequently found in nonsurvivor group (76.5%) compared to the survivor group (34.8%, P = 0.009). The use of mechanical ventilator was also significantly higher in nonsurvivor group (64.7%) than in the survivor group (26.1%, P = 0.015). The mean P/F ratio was significantly lower in the nonsurvivor group (197 ± 123 vs. 323 ± 119, P = 0.003). The median lactate levels were also significantly higher in the nonsurvivor group compared to the survivor group (P = 0.002). The median RDW was higher in the nonsurvivor group (P = 0.001). There is a moderate correlation between RDW and lactate (r = 0.532, P < 0.001) as presented in [Table 3]. RDW has negative correlation with hemoglobin (r = −0.471, P = 0.002) and P/F ratio (r = −0.298, P = 0.062).
| Discussion|| |
Lactic acidosis is a broad anion gap metabolic acidosis caused by either overproduction or underutilization of lactate. Overproduction of lactate occurs when the body generates (adenosine triphosphate) ATP without oxygen such as in tissue hypoxia. Underutilization of lactate involves decreased removal of lactic acid. Lactate levels have been used as an indicator of severity and prognosis in patients with acute shocks, in particular, and in critically ill patients, in general.
High blood lactate levels are found in critically ill patients with shock of any etiology and sepsis due to various reasons. Various other illnesses can cause an increase in the blood lactate levels such as acute lung/liver injury, severe asthma, poisoning, and postcardiac surgery. Hyperlactatemia is a cardinal finding of sepsis and septic shock. It is said that the mechanism of hyperlactatemia for the two conditions is different. In sepsis, the increased lactate levels represent the increased glycolytic flux due to hypermetabolism, while in septic shock, the increase in glycolytic flux is because of tissue hypoxia. This suggests that there are two varieties of lactate: stress lactate and shock lactate.
Our data demonstrate that RDW at the time of PICU admission differs significantly between the survivor and nonsurvivor groups. The nonsurvivor group tends to have higher RDW value compared to the survivor group (P = 0001). A study by Ramby et al. found that RDW was independently associated with PICU mortality (OR: 1.25, 95% CI: 1.09–1.43). Another study in Indonesia with the subject population pediatric patients with sepsis found that patients with elevated RDW had higher mortality rate compared to normal RDW group (45% vs. 40%), but the difference was not significant (relative risk: 1.12, 95% CI: 0.55–2.32, P = 0.749).
There were limited studies of RDW in the pediatric population. In adults, RDW has been known as a prognostic marker in patients with critical illness, sepsis, congestive heart failure, acute myocardial infarction, pulmonary embolism, pneumonia, cardiac arrest, and stroke. In a study by Bazick et al., RDW was a strong predictor of all-cause mortality, with 2.8- and 5.0-fold higher of mortality in patients with RDW values in the fourth (RDW 14.7%–15.8%) and fifth highest quintiles (RDW >15.8%), compared to those in the bottom quintile (RDW <13.3%).
RDW is a measure of the variability in the size of circulating RBCs. RDW could be elevated in any condition in which RBCs are produced ineffectively or increasingly destructed, which result in the release of reticulocytes, and several mechanisms have also been suggested. As predicted, RDW was inversely correlated with hemoglobin in this study (r = −0.472, P = 0.002). Elevation of RDW in sepsis may be associated with inflammation. Pro-inflammatory cytokines such as tumor necrosis factor α, interleukin-6, and interleukin-1β could suppress RBC maturation and decrease the half-life of RBCs. Therefore, the inflammatory response could lead to elevated RDW. In addition to inflammation, oxidative stress and neurohormonal response in sepsis might contribute to reduce the half-life of RBC and induce accelerated RBC production, resulting in an increase of RDW.,
An increased RDW can be linked to hypoxemia. A transient decrease in PaO2 will lead to erythropoietin release through hypoxia-inducible transcription factors. These will trigger the release of immature reticulocyte into the circulation, leading to anisocytosis and a higher RDW. Supporting this hypoxemia–anisocytosis pathway, elevated RDW values have been found in diverse respiratory disease. Schepens et al. reported that patients with higher RDW upon admission are associated with a greater need for invasive mechanical ventilation, lower 28-day ventilator-free days, and lower P/F ratios. In this study, RDW and P/F ratio had weak-negative correlation (r = −0.298, P = 0.062), meaning the higher RDW correlates with lower P/F ratio, supporting the hypoxemia–anisocytosis theory.
An increase in lactate concentration to >1.5 mEq/L is associated with a higher mortality rate. In this study, we found that the median lactate level during admission was higher in the nonsurvivor group compared to the survivor group (4.3 vs. 1.2, P = 0.002). It was in accordance with P/F ratio value which is significantly lower in the nonsurvivor group, indicating a more hypoxemia condition in the nonsurvivor group. In condition of hypoxemia, cells undergo anaerobic metabolism and thus will result in increased blood lactate level.
This study found that the nonsurvivor group had both higher RDW and higher lactate level compared to the survivor group. Spearman correlation test was used to determine whether there was a linear correlation between RDW and lactate. There was a moderate and significant correlation between RDW and lactate level (r = 0.532, P < 0.001). It stated that high RDW correlates with high blood lactate level. This association might occur since both RDW and lactate increased in similar condition such as hypoxemia, inflammation, and altered tissue perfusion, which are found in various underlying diseases in critically ill patients. This correlation supports previous studies that RDW might be used as a prognostic marker in critically ill patients.
There are several limitations to this study. RDW and lactate were only measured once during admission; therefore, they might not reflect the improvement or worsen of the condition. The patient presented with acute illness might not show an increase in RDW value. There is a need to perform serial RDW and lactate measurements. Larger sample size would allow stratification based on RDW quartile, more allowing for subject-matching based on diagnosis, age, and gender. The degree of inflammation should be measured using one inflammatory marker such as C-reactive protein or procalcitonin.
| Conclusion|| |
There was moderate and significant correlation of RDW and serum lactate level in critically ill pediatric patients. An increase in RDW value was associated with an increased lactate level. This result showed RDW as a promising prognostic marker in critically ill patients.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]