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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 3  |  Page : 99-103

Correlation of red cell distribution width value with the duration of mechanical ventilator usage in patients treated in pediatric intensive care unit


1 Department of Child Health, Udayana University, Denpasar, Bali, Indonesia
2 Department of Anesthesiology and Intensive Care, Udayana University, Denpasar, Bali, Indonesia

Date of Submission19-Mar-2020
Date of Decision01-May-2020
Date of Acceptance12-May-2020
Date of Web Publication18-Jul-2020

Correspondence Address:
Dr. Christopher Ryalino
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Udayana University, Denpasar, Bali
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/BJOA.BJOA_27_20

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  Abstract 


Background: Red cell distribution width (RDW) is the coefficient of erythrocyte volume variation. High RDW may indicate heterogeneous erythrocyte size in terms of size and volume (anisocytosis). RDW is affected by the degree of hypoxic tissue; the higher the hypoxia, the higher the RDW. The goal of the study was to see the correlation between RDW and the duration of ventilator usage on patients treated in the intensive care unit. Patients and Methods: This study employed a cross-sectional design. The participants of this research are children treated with mechanical ventilator in the pediatric intensive care unit (PICU) in Sanglah General Hospital from January to December 2018. The duration of mechanical ventilator usage and RDW value data was generated from the medical records. Results: There were sixty patients treated in the PICU during the study period, including 24 females (40%) and 36 males (60%). The average of oxygen index (OI) was 6.9 (0.9–20.57) and ventilator usage duration was 7.43 (1–32). Analysis of correlation between RDW and hemoglobin (Hb), FiO2, positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), mean airway pressure, OI, and days of ventilator usage revealed that RDW has a strong positive correlation with Hb (r = 0.43), FiO2(r = 0.82), PEEP (r = 0.17), PIP (r = 0.41), OI (r = 0.76), and days of ventilator usage (r = 0.87). The result of a subgroup analysis of days of ventilator usage had a strong positive correlation with RDW. In mild-degree pediatric acute respiratory distress syndrome, the correlation score was r = 0.89, moderate degree was r = 0.766, and severe degree was r = 0.71. Conclusion: There is a strong positive correlation between RDW and the duration of mechanical ventilator usage.

Keywords: Mechanical ventilator, red cell distribution width, ventilator duration


How to cite this article:
Budi Hartawan I N, Saputra Y, Ryalino C. Correlation of red cell distribution width value with the duration of mechanical ventilator usage in patients treated in pediatric intensive care unit. Bali J Anaesthesiol 2020;4:99-103

How to cite this URL:
Budi Hartawan I N, Saputra Y, Ryalino C. Correlation of red cell distribution width value with the duration of mechanical ventilator usage in patients treated in pediatric intensive care unit. Bali J Anaesthesiol [serial online] 2020 [cited 2020 Sep 30];4:99-103. Available from: http://www.bjoaonline.com/text.asp?2020/4/3/99/290090




  Introduction Top


Red cell distribution width (RDW) is the coefficient of erythrocyte volume variation. High RDW may indicate heterogeneous erythrocyte size in terms of size and volume (anisocytosis). RDW can be calculated as RDW-standard deviation (RDW-SD) and RDW coefficient variation. RDW-SD is the actual scale in terms of erythrocyte width in fL unit.[1],[2]

RDW examination is a part of a complete blood panel examination, usually performed to evaluate clinical conditions such as anemia, autoimmune disease, sepsis, heart problems, lung problems, and neonates. Increased RDW is found in iron deficiency anemia, folic acid deficiency anemia, and B12 vitamin deficiency anemia. Increased RDW may be a strong predictor of morbidity and mortality in patients with chronic heart failure, similarly in sepsis patients.[2]

Patients with a respiratory problem such as pneumonia and asthma experience oxygen exchange disturbance that causes tissue hypoxia. Hypoxia in tissue can increase the RDW in conjunction with acute fall of partial pressure of oxygen (PaO2) mechanism, which triggers the renal cortex to excrete erythropoietin (EPO). EPO induces erythropoiesis in renal marrow by suppressing apoptosis and therefore increasing the number of red blood cells (RBCs). A significant increase of RDW is noted in patients with pneumonia, which lasts for a few days up to 1 week after therapy.[2]

Researches regarding the correlation between RDW and mechanical ventilator usage were carried out in some countries. One USA-based study reported that 637 samples of children treated in a pediatric intensive care unit (PICU) revealed that children with RDW value higher than >14.5% have a longer ventilator usage duration with an average ventilator usage of 12 days (P < 0.001).[3] Another study in Belgium revealed that the average RDW value of children treated with ventilator is 14.8%, with a duration of 10-day ventilator usage.[4] Increase in RDW is related with the 28 low ventilator-free days (P = 0.003), mechanical ventilator needs, and ventilators' usage with >4-day duration.[4]

In contrast to those studies, a Chinese-based study in 2017 with 362 children treated in PICU using ventilator (average duration 16.5 h), found that there was no statistically significant difference between the duration of ventilator usage and increasing RDW value (P = 0.008).[1] This result was also supported by a study held in Indonesia by Devina et al.,[3] who reported RDW media value to be 14.8% (11.2%–27.8%) and not correlated with hemoglobin (Hb) level (r = 0.056, P = 0.73). Mortality event in normal and increased RDW groups was 40% and 45%, respectively. There was no statistically significant correlation between RDW groups with the mortality occurrence (P = 0.749) and treatment duration (P = 0.280).

A mechanical ventilator is routinely given to children with hypoxia in the intensive care unit. The mechanical ventilator can provide adequate ventilation and oxygenation, leading to improved partial pressure of oxygen (PaO2), partial pressure of carbon dioxide, oxygen saturation, and balanced pH.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]

Up to the current period, studies regarding the correlation between RDW and mechanical ventilators generated various results. Therefore, researchers are interested in performing a study regarding the correlation between RDW and the duration of ventilator usage on patients treated in the intensive care unit.


  Patients and Methods Top


This study employed a cross-sectional design from January 2018 to May 2018 in Sanglah General Hospital, Bali, Indonesia. The target population was all children treated using ventilator in the PICU. The inclusion criteria were all children treated with mechanical ventilator recorded from the medical records. The exclusion criteria were those with incomplete data of the medical records and children with cyanotic congenital heart disease. The study protocol was approved by the Ethical Research Committee of Udayana University/Sanglah General Hospital.

RDW was taken from a complete blood count (CBC) test result. The duration of ventilator usage is the total days of mechanical ventilator usage stated in days. Patients with mechanical ventilator are patients who are endotracheally intubated and are using mechanical ventilator in the PICU. FiO2 is defined as oxygen fraction given initially by the mechanical ventilator stated in percentage unit. Oxygen index (OI) is calculated using the following formula: (FiO2 × mean airway pressure [MAP] × 100)/PaO2 and further classified as pediatric acute respiratory distress syndrome (pARDS) mild degree (OI: 4–8), moderate degree (OI: 8–16), and severe degree (OI: >16). The score was generated from mechanical ventilators and results of blood gas analysis to classify if such child suffers pARDS.

The sample size was calculated using the standard sample size formula of the correlation of two numerical variable hypothesis, which resulted 60 as the minimum number of patients. The raw data were then analyzed using computer, which were later on presented in narration and table. Statistical tests were performed using descriptive statistics to value the patient's characteristics. Spearman's correlation test was performed to prove the correlation between RDW and duration of ventilator usage. P < 0.05 was considered statistically significant. This research obtained approval from the Ethical Research Committee of Sanglah General Hospital.


  Results Top


A total of sixty patients were involved in this research, consisting of 24 (40%) females and 36 (60%) males. The basic characteristics are shown in [Table 1]. The CBC test was performed on sixty patients in the emergency department; parameters reviewed were parameters related with oxygenation such as RBC, Hb, and RDW. The mean RBC was 3.98 (1.92–6.01), Hb was 10.49 (5.13–15.85), and RDW was 15.9 (10.3–24.9).
Table 1: Characteristic of the patients (n=60)

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An analysis of correlation between RDW and Hb, FiO2, positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), MAP, OI, and days of ventilator usage revealed that RDW is strongly and positively related with Hb (r = 0.43), FiO2(r = 0.82), PEEP (r = 0.17), PIP (r = 0.41), OI (r = 0.76), and days of ventilator usage (r = 0.87). The correlation analysis is shown in [Table 2]. A subgroup analysis was performed to confirm the correlation between RDW based on the pARDS degree and ventilator usage duration. On mild-degree pARDS, the correlation score was noted as r = 0.89, moderate degree as r = 0.766, and severe degree as r = 0.71.
Table 2: Correlation of red cell distribution width with observed variables

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  Discussion Top


This research involved 38 infants (63.3%) treated with ventilators. The average age of the infants was 36.8 months. The result of this research is related to the growth and maturation of the alveoli. Alveoli are mature in age approaching 5 weeks. Two types of cells which are pneumocyte cell type 1 and 2 play an important role in pulmonary maturation. Pneumocyte 1 is in charge of gas exchange, whereas pneumocyte 2 produces surfactant. Infants aged below 5 weeks have a thin-type 1 pneumocyte cell, “primitive saccule.” In the septa growth process, pneumocytes undergo remodeling where the total cell count is increasing and forming a capillary loop, which creates a complex that plays an important role in the gas exchange.[14]

This research involved more male patients (60%). This finding was in line with a research performed in India by Chhajed in 2017 on 72 children treated with mechanical ventilator in the PICU. The researchers noted that more males used the mechanical ventilator compared with females, with a ratio of 1.25:1.[15] This research shows that males are more susceptible to critical diseases. Sexual hormones play a role in the development of the lung, proven by the receptor for androgen found in the mesenchyme cell of the lung. Androgen and estrogen are against each other in the development of the lung. Androgen hampers surfactant production in males through a mechanism that involves transforming growth factor-beta. In females, the estrogen receptor is found in the alveoli. Estrogen triggers pneumocyte cell type 2 to excrete surfactant, and therefore female alveoli mature faster.

Underlying diseases in this research are community pneumonia in 24 patients (40%), sepsis in 13 patients (21.6%), meningitis in 4 patients (6.7%), Intracranial bleeding (ICB) in 4 patients (6.7%), and hospital-acquired pneumonia (HAP) in 3 patients (5%). This result was supported by some researches in Spain in 2004 with a total sample of 33 children who were treated using mechanical ventilator because of acute respiratory failure (46.5%), chronic respiratory failure (10.4%), coma (11.6%), and patients who required mechanical ventilation postoperatively (10.5%). A study conducted in Turkey in 2016 with a total sample of 91 children also showed similar results with underlying diseases such as respiratory problem in 64.8%, heart problems in 19.7%, central nervous system disturbances in 9.8%, and safety airway in 5.4%.[5],[6] A latest research in Brazil in 2006 conducted on 1185 children using mechanical ventilator noted that the indications of children using mechanical ventilator I are acute respiratory failure in 78%, followed by loss of consciousness in 15%, and chronic pulmonary disease in 6%.[7] pARDS is the main indication of using mechanical ventilator. pARDS is further classified into three degrees, namely, mild, moderate, and severe based on the OI calculation.

This research involved 26 (43.3%) children treated due to mild-degree PARDS, 9 children (15%) with moderate degree, and 7 children (11.7%) with severe degree. Farias et al. in 2005 found that the main sources of PARDS are pneumonia (35%), aspiration (15%), sepsis (13%), near-drowning (9%), and heart problems (7%).[8] Pneumonia is due to microorganism invasion to alveoli. Phagocytized-bacteria induced inflammation reaction which conducted by TNF-alfa and IL-12, resulting exudate which contains fibrin inside the alveoli cavity, causing alveoli cells to stick to each other. Inflammation stimulates neutrophil to proliferate, resulting in necrosis of alveoli, therefore fibrosis and pulmonary edema are formed. High fibrin exudate then interferes with the oxygen exchange, wherein the severe degree usually requires a ventilator.[16]

Ventilator usage is important in ARDS. The main purpose of mechanical ventilator usage is to normalize the arterial blood gas level and the acid–base balance by giving adequate ventilation and oxygenation. Until now, there is no specific ventilator setting for ARDS patients; in common practice, the setting is based on clinical conditions and the result of blood gas analysis. The mean of FiO2 was 74.5% (25%–100%), PEEP was 6 cmH2O (13–20), and MAP was 10.64 cmH2O (8.3–14.2). The ventilator setting was set lower in this study compared to a research by Newth et al. in the United States of America in 2017. A study reported the characteristic in pediatric patients who suffered from ARDS and required ventilators in 121 children. They found that the FiO2 was found to be 60% (40%–80%), PEEP was 7 cmH2O (5–10), and PIP was 27 cmH2O. The PIP value may rise to 29–32 cmH2O with damaged lung compliance. PIP is the pressure that is given above the PEEP pressure to prevent barotrauma. This recommendation is in accordance with our research where the maximal inspiration pressure given was 28 cmH2O (18–28). Rimensberger recommends PEEP of 10–15 cmH2O, which could be lowered based on oxygenation and hemodynamics. The purpose of giving PEEP is to prevent the lungs from collapsing at the end of expiration (prevent atelectasis). Two meta-analyses noted that high PEEP could lower mortality in adult patients, however this has not been tested on pediatric patients. Until now, the average PEEP given is 6–8 cmH2O, which is in line with our research where the median of distributed PEEP is 6 cmH2O.[9]

The average Hb level during patient treatment was 10.49 g/dL. Other researchers noted that Hb level of >8 g/dL has lower duration of ventilator usage (odds ratio, 2.95; 95% confidence interval, 0.88–9.96).[10] Hb level is related to RDW value. If the Hb level is low, the tissue will suffer hypoxia and the hypoxia will stimulate the kidney to excrete EPO. EPO will stimulate the bone marrow to produce RBC. Our research noted moderate correlation between RDW level and Hb (r = 0.43).[16]

The average duration of ventilator usage within this research was 1–32 days with a mean of 7.43 days. The RDW value ranged between 10.3 and 24.9 (15.9%). Ventilator usage duration is strongly positively correlated with RDW; the correlation coefficient between these two variables is 0.87. Based on these results, it can be said that the higher the RDW, the longer the duration of ventilator usage in the patient. The result of this research is supported by Schepens et al.'s research in 2017, which is a retrospective cohort research conducted on 960 children treated in the PICU. The result of the research shows that 145 of the patients had increased RDW by 13.8% (interquartile range 13.0–15.1%). Increased RDW is related to lower ventilator-free days (28 days) (P = 0.003), mechanic ventilator requirement, and the ventilator usage duration of >4 days.[3] Another study reported that 673 patients treated in the ICU found that increased RDW (≥14.5%) is associated with longer treatment duration and longer ventilator usage by 16% compared with the RDW value of <14.5%.[4],[16]

A strong correlation between RDW and Hb and duration of ventilator usage is caused by tissue hypoxia mechanism. Some researchers noted that increase in RDW is related to higher RBC productivity due to EPO stimulation in hypoxia condition. Hypoxia causes EPO spikes, resulting in macrocyte and normocyte discharge simultaneously, which is noted as the increment of RDW. EPO surge not only increases the speed of RBC production, but also increases the RBC size. The higher the EPO surge, the bigger the RBC size. RBC size gets increased by 0.5%–0.25% after the EPO surge. RBC with a bigger size (>120 fL) does not deliver oxygen as it supposed to be and has a lower life span of 1–2 months.

Besides affecting the size and the production speed of RBC, EPO also stimulates primitive RBC (neonatal RBC [nRBC]) to circulation. Primitive RBC has Fetal hemoglobin (HbF) with lower affinity to oxygen compared to HbA2 in normal RBC. nRBC is related to oxygen saturation, with only minimal amount; it could lead to severe desaturation which is a high mortality predictor in chronic disease. Hypoxia should be treated to normalize the RDW value; ventilator is required in severe lung problems. Increased RDW follows the acute response to hypoxia. However, in a condition where hypoxia has been treated, but RDW is not normal yet, this will relate to the age of RBC. The higher the RDW, the longer the duration required for RDW to return to normal value.

The weaknesses of this study were the lack of anemia history taking in the patient and some underlying diseases that affect the homogeneity of the research sample. Therefore, further research with more specific subject criteria is required.


  Conclusion Top


This study found a strong positive correlation between RDW and the duration of mechanical ventilator usage.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Zuk M, Migdal A, Dominczak J, Brzezinska-Rajszys G. Usefulness of red cell width distribution (RDW) in the assessment of children with pulmonary arterial hypertension (PAH). Pediatr Cardiol 2019;40:820-6.  Back to cited text no. 1
    
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Otero TMN, Yeh DD, Bajwa EK, Azocar RJ, Tsai AL, Belcher DM, et al. Elevated red cell distribution width is associated with decreased ventilator-free days in critically ill patients. J Intensive Care Med 2018;33:241-7.  Back to cited text no. 2
    
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Devina T, Lubis M, Mutiara E, Yanni GN, Saragih RAC, Trisnawati Y, et al. Red cell distribution width and mortality in pediatric sepsis. Paediatrica Indonesiana. 2016;56:320-4.  Back to cited text no. 3
    
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Schepens T, De Dooy JJ, Verbrugghe W, Jorens PG. Red cell distribution width (RDW) as a biomarker for respiratory failure in a pediatric ICU. J Inflamm (Lond) 2017;14:12.  Back to cited text no. 4
    
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Yčas JW, Horrow JC, Horne BD. Persistent increase in red cell size distribution width after acute diseases: A biomarker of hypoxemia? Clin Chim Acta 2015;448:107-17.  Back to cited text no. 13
    
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