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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 3  |  Page : 350-354

Red cell distribution width predicts new-onset atrial fibrillation in sepsis patients


Department of Anesthesia and Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission20-Sep-2018
Date of Acceptance05-May-2019
Date of Web Publication29-Aug-2019

Correspondence Address:
MD Ahmed M Elsayed
Department of Anesthesia and Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, 38 Abbasia Square, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/roaic.roaic_74_18

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  Abstract 

Background Sepsis is a major cause of mortality in non-cardiac intensive care units, and ranks 10th among causes of death overall. Acute new onset atrial fibrillation is a common observation in critically ill patients admitted with sepsis, there is a direct relationship with disease severity. The red cell distribution width variations reflects a range of systemic diseases including heart failure, stable coronary disease, acute coronary syndrome and stroke.
Objectives In this study, we aimed to investigate the relation between red cell distribution width (RDW) and atrial fibrillation (AF) in critically-ill patients with sepsis.
Settings and Design We retrospectively examined 70 sepsis patients (35 sepsis patients with newly developed AF during intensive care unit (ICU) stay and 35 sepsis patients without AF matched with age and sex. We investigated the predictive potential for atrial fibrillation for RDW, Ejection fraction, central venous pressure (CVP), Heart rate and qSofa score.
Results The mean age of AF group was 54.49 ± 10.07 vs. 56.26 ± 11.766 for Non-AF group. Baseline Ejection fraction, systolic blood pressure, heart rate and CVP showed no significant differences. RDW on admission was significantly different between groups; 18.94 ± 1.126 (AF group) vs. 14.76 ± 0.97 (Non AF Group). ROC curve analysis was done on AF group to determine cut-off values for RDW. Cut-off point was at 17.6 with 97 % sensitivity and 60.7 % specificity.
Conclusions RDW levels were higher in sepsis patients with newly developed atrial fibrillation. An increased RDW level in the patient with sepsis may alert physician on developing or presence of atrial fibrillation.

Keywords: atrial fibrillation, quick sequential organ failure assessment, red blood cell distribution width, sepsis


How to cite this article:
Ibrahim DM, Anis SG, Elsayed AM. Red cell distribution width predicts new-onset atrial fibrillation in sepsis patients. Res Opin Anesth Intensive Care 2019;6:350-4

How to cite this URL:
Ibrahim DM, Anis SG, Elsayed AM. Red cell distribution width predicts new-onset atrial fibrillation in sepsis patients. Res Opin Anesth Intensive Care [serial online] 2019 [cited 2019 Nov 21];6:350-4. Available from: http://www.roaic.eg.net/text.asp?2019/6/3/350/265728


  Key Messages Top


Nowadays, there is a milieu of markers related to sepsis and sepsis-associated conditions. These include presepsin, preadrenomedullin, hs-crp and mean platelet volume among others. In this study we investigate the potential of a simple, inexpensive marker -red cell distribution width- to predict recent onset atrial fibrillation in the intensive care environment.


  Introduction Top


Sepsis is a serious condition characterized by disturbances in normal body homeostasis due to altered response to infection. It is a major cause of mortality in noncardiac ICUs, and ranks 10th among causes of death overall [1]. Septic shock is a variant of sepsis with a higher mortality rate. It is associated with hemodynamic, cellular, and metabolic changes [2].

Acute atrial fibrillation (AF) is a common observation in critically ill patients admitted with sepsis; there is a direct relationship with disease severity [3].

Of all causes of arrhythmia, AF is the most significant with prevalence higher in intensive care unit (ICU) patients than the general population with differences according to each type of ICU. The incidence in general ICUs ranges from 4 to 9%, in contrast to postcardiotomy patients, where it rises from 32 to 50%. This could be attributed to the dual origin of AF, cardiac and noncardiac. Cardiac causes include age, ischemic heart disease, and essential hypertension. On the other hand, noncardiac AF is usually precipitated by inflammation [3].

In addition, recent-onset AF helps predict mortality in heart failure patients. Despite not being a direct cause of death in these patients, the sudden decline in cardiac output and increased filling pressures is probably a contributor to worsened cardiac function. Furthermore, critically ill patients with new-onset AF may have thromboembolic complications − albeit with lesser frequency − similar to chronic AF patients [4].

Erythrocytes, commonly known as red blood corpuscles, are blood elements lacking a nucleus and exhibit an oval biconcave morphology [5].

Red blood cell (RBC) volume is normally between 80 and 100 fl. Certain physiological (e.g. pregnancy and aging) and pathological (e.g. hemolytic anemia, and thalassemia) conditions cause higher RBC volumes as a result of impaired erythropoiesis with appearance of larger (≤120 fl) and smaller (<60 fl) elements, a process known as anisocytosis [5].

The red cell distribution width (RDW) is calculated by dividing erythrocyte volume standard deviation (SD) by the mean corpuscular volume. The result is expressed in either a numerical value or as a percentage which is the more widely used method. There is enough evidence to suggest that in addition to common RBC disorders, RDW variations also reflect a range of systemic diseases [5].

Among the conditions reported with elevated RDW levels are heart failure, acute coronary syndrome, sluggish coronary flow, and noncardiac diseases such as cerebrovascular stroke [6].


  Aim Top


In this study, we aimed to investigate the relation between RDW and AF in critically ill patients with sepsis.


  Patients and methods Top


This retrospective, observational study was carried out in Ain Shams University Hospitals between January 2017 and January 2018.

After obtaining medical ethics committee approval (number R33/2018) with a waiver on individual patient consent, 70 patients aged between 18 and 65 years of both sexes were enrolled. They were admitted to the general ICU of Ain Shams University Hospitals with diagnosis of sepsis or septic shock. The study was registered in ClinicalTrials.gov trial registry (NCT03523676).

Result reporting adheres to STROBE statement for observational studies with references to STROBE statement and the broader EQUATOR guidelines [7].

Study design

Groups of patients

Patients enrolled in the study were allocated into two groups according to the presence of newly developed AF.

The method used for the selection of candidates in this study was consecutive sampling, a type of nonprobability assessment.

Group A

A total of 35 sepsis patients who did not develop AF during ICU stay.

Group B

A total of 35 sepsis patients with newly developed AF during ICU stay.

The inclusion criteria were as follows: for all patients according to Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [2], adult patients with suspected infection were identified, having quick Sequential Organ Failure Assessment (qSOFA) score meeting of more than or equal to 2 of the following criteria: respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mmHg or less [2].

For group B, in addition to the aforementioned criteria, patients with newly developed AF during ICU stay were retrospectively selected.

All patients with concomitant valvular disease, cardiomyopathy, cardiac dysrhythmias, previous cardiac surgery, secondary hypertension, hyperthyroidism, severe head injury, stroke, coma, acute coronary artery disease, severe liver disease (Child–Pugh grade C), and chronic renal failure were excluded from the study. In addition, pregnant patients were excluded from the study.

All patients were managed according to the Surviving Sepsis Guidelines 2017.

Venous samples were obtained from all patients on admission for complete blood count (CBC), liver profile, renal profile, and coagulation profile.

Laboratory tests

Daily CBC analysis including hemoglobin concentration, platelets, white blood cells, and RDW was performed using SYSMEX XN-550 automated analyzer (SYSMEX Corporation; Kobe, Japan).

Serum creatinine and blood urea nitrogen were measured on a daily basis, while alanine aminotransferase, aspartate aminotransferase, and serum albumin were measured every other day. Prothrombin time, international normalized ratio, and partial thromboplastin time were measured every 4 days.

Baseline electrocardiogram (ECG), chest radiograph, and echocardiography were done for all patients.

Sample power

Using STATA program version 10.0 (Stata statistical software: release 10; StataCorp LP., College Station, Texas, USA) setting α error at 0.05, power at 90%, the result of the previous study by Sarıkaya et al. [6] showed that the mean RDW with AF cases was 15.1±1.5, for the other group it was 14.05±1.15. On the basis of these findings, the required sample size was determined to be 35 cases.

Statistical analysis

The statistical analysis was performed using a standard SPSS software package version 17 (SPSS Inc., Chicago, Illinois, USA). Normally distributed numerical data are presented as mean±SD and the differences between groups were compared using the independent Student’s t-test; data not normally distributed were compared using the Mann–Whitney test and are presented as median (interquartile range) and categorical variables were analyzed using the χ2-test or Fisher’s exact test and are presented as number. All P values are two-sided. P value less than 0.05 is considered statistically significant.

Receiver operating characteristic curve analysis was done using MedCalc software version 14.8.1 (MedCalc Software bvba, Ostend, Belgium).


  Results Top


Patients’ characteristics and clinical diagnosis

There were no statistically significant differences between patients of both groups as regards age, sex, height, and weight. The mean age of the AF group was 54.49±10.07 versus 56.26±11.766 for the non-AF group. Baseline ejection fraction, systolic blood pressure, heart rate, and central venous pressure (CVP) showed no significant differences.

RDW on admission was significantly different between groups; 18.94±1.126 (AF group) versus 14.76±0.97 (non-AF group); similarly alanine aminotransferase showed significant differences between groups on admission: 22.77±4.84 (AF group) versus 29.23±6.68 (non-AF group) ([Table 1]).
Table 1 Patient characteristics and demographic data

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Moreover, there were no statistically significant differences between both groups regarding the causes of sepsis and percentage of septic shock ([Table 2]).
Table 2 Causes of sepsis and percentage of septic shock

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qSOFA score results were comparable between both groups with exception to the third and seventh days there were statistically significant differences, with higher values in the AF group than the non-AF group ([Table 3]).
Table 3 Quick Sequential Organ Failure Assessment score

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RDW values were higher in AFsignificantly group than non-AF group over the whole study period ([Table 4]).
Table 4 Red cell distribution width

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Analysis of data by multivariate logistic regression showed that RDW was the only independent risk factor for AF in the study population (odds ratio: 60.0769; 95% confidence interval: 3.4156–1056.6902; P<0.05; [Table 5]).
Table 5 Predictors of atrial fibrillation

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Receiver operating characteristic analysis was done on patients who developed AF to determine cutoff values for RDW. The cutoff point was at 17.6 with 97% sensitivity and 60.7% specificity ([Figure 1]).
Figure 1 Receiver operating characteristic curve.

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  Discussion Top


Sepsis is associated with some serious complications including new-onset AF. The aim of this study was to identify the relationship between a blood analysis marker, RDW, and the ability to predict onset of acute AF in critically ill patients admitted with sepsis with qSOFA score more than or equal to 2, excluding patients with major systemic complications.

RDW is a simple, cheap, and readily available marker. Predictive ability of RDW was demonstrated in different publications in other patient groups.

In this study, RDW was the only independent risk factor of new-onset AF among patients included in the study.

The usefulness of RDW in predicting AF in hypertensive patients was noted by Sarıkaya and colleagues. He retrospectively examined 126 patients and found out that RDW and left atrial dimensions were the only independent risk factors for the development of AF.

Similarly Ertaş et al. [8] conducted a retrospective study on 132 patients undergoing nonemergency coronary artery bypass graft (CABG). A subset of inflammatory markers was used to assess their association with postoperative AF. They found that preoperative AF was associated with increased risk for new-onset AF after CABG.

Korantzopoulos et al. [9] pointed to the relationship between RDW variation and AF after cardiac surgery. Similar to our study, they found that RDW was the only independent risk factor for AF.

Cutoff values for RDW at which AF starts to occur seem to vary according to the underlying etiology. It was reported to be 14 195 in hypertensive patients [6] and 13.35 in post-CABG patients [8].

In this study, the cutoff value for AF in sepsis patients admitted to the ICU was 17.6 with 97% sensitivity and 60.7% specificity.Several theories have been proposed to describe the relationship between elevated RDW values and negative sequelae. One such mechanism is that elevated RDW impairs microcirculation by decreasing RBC deformability leading to tissue ischemia [10].

Another theory links high RDW values with oxidative stress, the latter stimulates erythropoiesis which leads to synthesis of large immature blood cells with poor oxygen transport properties leading to hypoxia [11].

A growing body of evidence suggests a relationship between AF and oxidative processes, which may include alteration in gene transcription, increases enzyme activity such as Nicotinamide adenine dinucleotide phosphate (NADPH) and xanthine oxidase and triggering of the renin–angiotensin system [12].

Furthermore, some authors have suggested a relationship between elevated RDW and limited physiological reserve with a higher incidence of complication, such as AF [13].

There are some shortcomings for this study. First, there are other inflammatory markers such as interleukin, tumor necrosis factor (TNF-α), and presepsin which might contribute to the development of AF that was not evaluated in this study.

We hypothesize that by adding or combining other inflammatory markers with RDW in quality-controlled trials we can reach a higher specificity and predictive power for AF.

Similarly, hemoglobin was the only measured factor while there are other factors which reflect RBC function such as iron, folate, and vitamin B12 levels. Lastly, the design of the study was observational and indicates an association between AF and RDW and not causality.

In brief, RDW is a readily available, cheap parameter that is routinely incorporated into the CBC; it has the potential to be used as a marker for the prediction of AF in this particularly frail subset of patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Rhee C, Klompas M. New sepsis and septic shock definitions: clinical implications and controversies. Infect Dis Clin North Am 2017; 31:397–413.  Back to cited text no. 1
    
2.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315:801–810.  Back to cited text no. 2
    
3.
Seguin P, Launey Y. Atrial fibrillation is not just an artefact in the ICU. Crit Care 2010; 14:182.  Back to cited text no. 3
    
4.
Kuipers S, Klouwenberg PM, Cremer OL. Incidence, risk factors and outcomes of new-onset atrial fibrillation in patients with sepsis: a systematic review. Crit Care 2014; 18:688.  Back to cited text no. 4
    
5.
Danese E, Lippi G, Montagnana M. Red blood cell distribution width and cardiovascular diseases. J Thorac Dis 2015; 7:E402.  Back to cited text no. 5
    
6.
Sarıkaya S, Şahin Ş, Akyol L, Börekçi E, Yılmaz YK, Altunkaş F et al. Is there any relationship between RDW levels and atrial fibrillation in hypertensive patient? Afr Health Sci 2014; 14:267–272.  Back to cited text no. 6
    
7.
Simera I, Moher D, Hoey J, Schulz KF, Altman DG. A catalogue of reporting guidelines for health research. Eur J Clin Invest 2010; 40:35–53.  Back to cited text no. 7
    
8.
Ertaş G, Aydin C, Sönmez O, Erdoğan E, Turfan M, Tasal A et al. Red cell distribution width predicts new-onset atrial fibrillation after coronary artery bypass grafting. Scand Cardiovasc J 2013; 47:132–135.  Back to cited text no. 8
    
9.
Korantzopoulos P, Sontis N, Liu T, Chlapoutakis S, Sismanidis S, Siminelakis S et al. Association between red blood cell distribution width and postoperative atrial fibrillation after cardiac surgery: a pilot observational study. Int J Cardiol 2015; 185:19–21.  Back to cited text no. 9
    
10.
Patel KV, Mohanty JG, Kanapuru B, Hesdorffer C, Ershler WB, Rifkind JM. Association of the red cell distribution width with red blood cell deformability. In: Welch J, Palm F, Bruley DF, Harrison DK, editors. Oxygen transport to tissue XXXIVW. New York, NY: Springer 2013. pp. 211–216.  Back to cited text no. 10
    
11.
Friedman JS, Lopez MF, Fleming MD, Rivera A, Martin FM, Welsh ML et al. SOD2-deficiency anemia: protein oxidation and altered protein expression reveal targets of damage, stress response, and antioxidant responsiveness. Blood 2004; 104:2565–2573.  Back to cited text no. 11
    
12.
Korantzopoulos P, Kolettis TM, Galaris D, Goudevenos JA. The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation. Int J Cardiol 2007; 115:135–143.  Back to cited text no. 12
    
13.
Hunziker S, Celi LA, Lee J, Howell MD. Red cell distribution width improves the simplified acute physiology score for risk prediction in unselected critically ill patient. Crit Care 2012; 16:89.  Back to cited text no. 13
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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