• Users Online: 348
  • Print this page
  • Email this page

 
Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 3  |  Page : 107-111

Predictive value of serum lactate dehydrogenase in diagnosis of septic shock in critical pediatric patients: A cross-sectional study


1 Pediatric Critical Care Department, Cairo University School of Medicine, Egypt
2 Department of Clinical and Chemical Pathology, Cairo University School of Medicine, Egypt

Date of Submission23-Jan-2021
Date of Decision07-Mar-2021
Date of Acceptance19-May-2021
Date of Web Publication31-May-2021

Correspondence Address:
Elshymaa Salah Ahmed
Pediatric Critical Care Department, Cairo University School of Medicine
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2221-6189.316674

Get Permissions

  Abstract 

Objectives: To determine the predictive value of lactate dehydrogenase (LDH) in diagnosis of septic shock and its association with other prognostic scores in critical pediatric patients.
Methods: A cross-sectional study was performed at Children’s Hospital of Cairo University between June 2019 and December 2019. A total of 200 pediatric patients were divided into the septic shock group [100 critically ill patients with septic shock from the pediatric intensive care unit (PICU)] and the control group (100 patients with only sepsis). LDH was determined in the first 24 hours of admission. The sensitivity and specificity of LDH in diagnosis of septic shock were assessed; the levels of related indicators of patients with different etiologies were compared; correlations between LDH, Paediatric Index of Mortality Π, and Pediatric Sequential Organ Failure Assessment (PSOFA) were analyzed.
Results: LDH was 512 μL (406.50-663.00) in the septic shock group and was significantly higher than that (190 μL, range 160.00-264.50) in the control group (P<0.001). Besides, median LDH in children with chest infecion was higher than that in children with other diagnoses (P=0.047). A good positive correlation was found between PSOFA and LDH (r=0.503, P<0.001).
Conclusions: LDH could be a potential inflammatory marker in diagnosis of septic shock and is valuable for PICU admission decisions.

Keywords: Lactate dehydrogenase; Septic shock; Pediatrics version of the SOFA score


How to cite this article:
Algebaly HF, Abd-Elal A, Kaffas RE, Ahmed ES. Predictive value of serum lactate dehydrogenase in diagnosis of septic shock in critical pediatric patients: A cross-sectional study. J Acute Dis 2021;10:107-11

How to cite this URL:
Algebaly HF, Abd-Elal A, Kaffas RE, Ahmed ES. Predictive value of serum lactate dehydrogenase in diagnosis of septic shock in critical pediatric patients: A cross-sectional study. J Acute Dis [serial online] 2021 [cited 2021 Jun 16];10:107-11. Available from: http://www.jadweb.org/text.asp?2021/10/3/107/316674


  1. Introduction Top


Many cascade reactions involved in severe illness (e.g. sepsis) always begin with the pro-inflammatory process[1]. Lactate dehydrogenase (LDH) is one of the anaerobic metabolic pathway enzymes. Its serum level is elevated in multiple conditions resulting from tissue damage[2]. Several studies recorded a significant increase in LDH serum levels very early in sepsis[3]. Also, LDH levels have been proposed as a marker for sepsis prognosis[4]. They showed that LDH serum level was prognostically elevated in cases of severe sepsis and septic shock, and it is considered as an index to assess the extent to which the tissue was affected[5].

LDH was found associated with 28-day mortality in patients with severe sepsis[6]. Also, it has shown that pH, LDH and heart rate were the most important factors to assess the progress and outcome of a septic patient[7]. LDH level was found to be a prognostic marker for severe illness in neonates (e.g. early neonatal sepsis)[8]. Others said that if the LDH levels were not improved within 48 h in patients with severe sepsis, patients will be more likely to die[4].

Recently, LDH is considered a valuable biomarker in the diagnosis and follow-up of SARS-Cov-2 infection. One study concluded that LDH was a useful biomarker in the evaluation of case severity and for monitoring its response to treatment[9]. Another recommendation is successive measurements of LDH, C-reactive protein (CRP), and procalcitonin (PCT) in pediatric patients with COVID-19 infection as they may help follow the course of the illness[10]. Although there are a lot of studies on LDH, they have not explained the relation between LDH and severity in pediatric patients with sepsis. Moreover, several prognostic scores such as Sequential Organ Failure Assessment (SOFA) score and Paediatric Index of Mortality (PIM II) score have been applied to assess the severity and predict the risk of death at PICU admission, which can be a guide for treatment and caring. PIM II was first developed by Slater et al. in 1997, updated in 2003[11]. Also, the Sepsis-Related Organ Failure Assessment was developed initially to assess organ conditions in critically ill adults[12]. Recently, a pediatrics version of the SOFA score (PSOFA) was developed for critically ill children[13]. The score is composed of 6 variables for respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems, respectively[12]. This study aims to determine the predictive value of LDH in diagnosis of septic shock and its relationship with other proven prognostic scores.


  2. Patients and methods Top


2.1. Study design

A cross-sectional, case-control study was performed at University Children Hospital from June 2019 till December 2019.

2.2. Ethical approval

The institutional review board at our institution approved our study with ethical approval No. I.101015.

2.3. Inclusion and exclusion criteria

We included patients with sepsis, severe sepsis, or septic shock who met the criteria of the American College of Critical Care Medicine[14]. The American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock 2012 defines septic shock by clinical signs, including hypothermia or hyperthermia, altered mental status, and peripheral vasodilatation (warm septic shock) or vasoconstriction with capillary refill time more than 2 seconds (cold septic shock) before hypotension occurs.

We excluded patients with lipid disorders, metabolic disorders, tumors, acute hemolytic anemia, chronic liver or kidney disease, and patients on steroid therapy.

2.4. Patients and grouping

Two hundred pediatric patients were grouped into the septic shock group (100 critically ill patients with septic shock from PICU) and the control group (100 patients with only sepsis).

2.5. Sample collection and assessments

The sample was taken for LDH assay as follows: 2 mL of whole blood were collected with plain tubes (BDO vacutainer). Samples were immediately centrifuged, and the serum was used for analysis through blood chemistry analyzer Dimension RXL M AX integrated chemistry system from Siemens Health care S.A.E, Germany I*. Principle of the enzymatic assay is that the reaction between pyruvate and Nicotinamide adenine dinucleotide dehydrogenase (NADH) is catalyzed by LDH to produce Nicotinamide adenine dinucleotide (NAD) and L-lactate: LDH+Pyruvate+NADH=L-lactate+NAD. The stronger the catalytic activity of LDH, the more NAD oxidation. It was estimated by measuring the decrease in absorbance at 340 nm.

Also, the PIM II score at the time of admission was calculated. Ten items with yes or no answers for these variables scored as 1 or 0. These variables were entered into the system (www.sfar.org/scores2/ pim22.html). The system calculates the mortality rate based on standard methods using logistic regression equations[11].

2.6. Statistical analysis

All data was analyzed using the Statistical Package Social Science (SPSS) version 16 and expressed as mean ± standard deviation (SD) or median and interquartile range (IQR). Differences in clinical and biochemical characteristics were analyzed by student’s paired and unpaired t-test and Mann-Whitney U test. Areas under curves was used to assess the specificity and sensitivity of LDH in diagnosis of spetic shock. Correlation analysis were conducted to determine the association between LDH and different parameters in the septic shock group. Kruskall Wallis H test was applied to assess the differences among diagnoses of septic shock regarding laboratory and clinical criteria. The significant level of this study was set at α=0.05.


  3. Results Top


CRP in the septic shock group was 46.3 (23.35-80.80) mg/L, which was significantly higher than that in the control group of 11.00 (1.60-24.00) mg/L (P<0.001). Serum glutamic-oxaloacetic transaminase (SGOT) in the septic shock group was 32.00 (22.00-56.50) μL, which was significantly higher than that in the control group of 23.00 (18.00-31.00) μL (P=0.001). Besides, LDH in the septic shock group was 512.00 (406.50-663.00) μL, which was significantly higher than that in the control group of (190.00 (160.00-264.50) μL (P<0.001) [Table 1]. The cutoff point of 272 μL of LDH was a potential adjuvant for clinical evaluation and differentiation of septic shock from sepsis only with a sensitivity of 91% and specificity of 77% [Figure 1].
Figure 1: Sensitivity and specificity curve for serum lactate dehydrogenase level. The area under curves is 0.9; Sensitivity: 91%; Sepecificity:77%; Green line: Reference line; Blue line: lactate dehydrogenase (μΙ)

Click here to view
Table 1: Comparison of the clinical and laboratory criteria of the two groups

Click here to view


Also, our study revealed that there was a good positive correlation between LDH and liver enzyme (SGOT and SGPT) (r=0.581, P<0.001; r=0.491, P<0.001, respectively), and creatinine (r=0.202, P=0.043). Besides, the higher the PSOFA score, the higher the LDH (r=0.503, P<0.001), unlikely with other score systems as PIM Π (r=0.034, P=0.738) [Figure 2] [Table 2].
Figure 2: Correlation between lactate dehydrogenase and Pediatrics version of the SOFA score. PSOFA: Pediatrics version of the SOFA score; LDH: Lactate dehydrogenase

Click here to view
Table 2: Correlation between LDH and different parameters in the septic shock group (n=100).

Click here to view


The results showed that the median of LDH in chest infection was higher than that in other diagnoses (P=0.047) [Table 3].
Table 3: Differences among diagnoses of septic shock regarding laboratory and clinical criteria

Click here to view



  4. Discussion Top


Last decade, a lot of biomarkers and scores have been developed for early diagnosis and assessment of severe illness in the Emergency Department[15]. LDH is the cornerstone in the diagnosis of different illnesses[16]. Erez et al. recorded a significant increase in serum level of LDH at the onset of sepsis[2].

In our study, the median value of LDH in patients with severe sepsis/septic shock was 512 μΙ. A neonatal study by Ozkiraz et al. described the usefulness of LDH and lactate in deciding to refer neonates who suffer from transient tachypnea of new born to high-level neonatal care before the clinical situation deteriorates[17].

In our study, the cutoff value of 276 μL. as a predictor for organ failure and the need for PICU admission with a sensitivity of 90% and specificity of 77% were able to distinguish septic shock and severe sepsis from sepsis only. Karlsson et al. concluded that LDH might be a significant value during the neonatal period, and its predictive value is more important than that of lactate. Preterm infants presented with a serum LDH level range of 500-700 μL with a cut-off of 600 μL were predicted to have a strong need for NICU admission[18].

Our study showed that LDH in chest infection was higher than that in other diagnoses (P=0.047). Another study shows LDH is a good biomarker for a limited list of diseases, mostly infections, particularly chest infection, tumor, liver metastases, and hematologic malignancies[19]. Hendya et al. showed in a case presented with community-acquired pneumonia, LDH, albumin, CRP, and neutrophils should be determined to give an idea about the course, prognosis, and complication[20]. Pleural fluid LDH is useful for assessing the severity of pediatric community-acquired pneumonia patients with mycoplasma pneumonia and fever lasting for >3 d had a high level of LDH and total leucocytic count[21]. LDH is usually used besides another marker and clinical criteria in the diagnosis of certain opportunistic infections, like pneumocystis crania pneumonia and toxoplasmosis[22], especially in patients suffering from AIDS[23]. Another report argued the specificity of LDH as it is highly increased within minutes of hypoxic-ischemic state occurring anywhere in the body[24]. However, we suggest its use in addition to other clinical signs of infection rather than to replace them to quantify sepsis severity.

Current study observed a good positive correlation between pSOFA and LDH, the higher the SOFA score, the higher the LDH (r=0.503, P<0.001). Similarly, García-Gigorro et al. concluded that SOFA and changes in the SOFA score over time are good tools for assessing and follow up critically ill patients in ICUs[25].

The high LDH level was associated with a bad outcome in the form of more admission days, a higher risk factor for in-hospital mortality[26]. Its level was not considered as a dependent risk factor for mortality in patients with sepsis[6]. The patients with serum LDH more than 1 000 μL also had a long hospital stay and multiple organ affection as evident by SOFA score[27]. This is in agreement with Chkhaidze et al., who found that SOFA scores are an excellent tool to assess the organ affection in critically ill patients while PIM II gives a good rank for diagnosis risk rather than specific organ involvement[28].

All in all, LDH could be a potential inflammatory marker in conjunction with the other clinical criteria to discriminate against critically ill children with severe sepsis. This can guide the decision of PICU admission.

Conflict of interest statement

The authors report no conflict of interest.

Authors’ contributions

H.A.F.A.: Creating idea of the work; A.A: Data collection; R.E.K.: Laboratory analysis; E.S.A.: Paper writing.

 
  References Top

1.
Van Eijk LT, Dorresteijn MJ, Smits P, Van der Hoeven JG, Netea MG, Pickkers P. Gender differences in the innate immune response and vascular reactivity following the administration of endotoxin to human volunteers. Crit Care Med 2007; 35(6): 1464-1469.  Back to cited text no. 1
    
2.
Erez A, Shental O, Tchebiner JZ, Laufer-Perl M, Wasserman A, Sella T, et al. Diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients. Isr Med Assoc J 2014; 16(7): 439-443.  Back to cited text no. 2
    
3.
Trepos E, Katodritou E, Roussou M. High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents. Eur J Haematol 2010; 85(2): 114-119.  Back to cited text no. 3
    
4.
Joe GZ, Gregory LL, Maroun RN, Mohammed D, Gary TK. Prognostic significance of elevated serum lactate dehydrogenase (LDH) in patients with severe sepsis. Chest 2004; 126(4): 873S.  Back to cited text no. 4
    
5.
Bekhit OE, Algameel AA, Eldash HH. Application of pediatric index of mortality version 2: score in pediatric intensive care unit in an Africandeveloping country. Pan Afr Med J 2014; 17: 185.  Back to cited text no. 5
    
6.
Lu J, Wei ZH, Jiang H, Cheng L, Chen QH, Chen MQ, et al. Lactate dehydrogenase is associated with 28-day mortality in patients with sepsis: a retrospective observational study. J Surg Res 2018; 228: 314-321.  Back to cited text no. 6
    
7.
Duman A, Akoz A, Kapci M, Ture M, Orun S, Karaman K, et al. Prognostic value of neglected biomarker in sepsis patients with the old and new criteria: predictive role of lactate dehydrogenase. Am J Emerg Med 2016; 34(11): 2167-2171.  Back to cited text no. 7
    
8.
Anh TN, Hao TK, Hoang HH. The role of plasma lactate dehydrogenase testing in the prediction of severe conditions in newborn infants: A prospective study. Res Rep Neonatol 2020; 10: 31-35.  Back to cited text no. 8
    
9.
Wu MY, Yao L, Wang Y, Zhu XY, Wang XF, Tang PJ, et al. Clinical evaluation of potential usefulness of serum lactate dehydrogenase (LDH) in 2019 novel coronavirus (COVID-19) pneumonia. Respir Res 2020; 21(1): 171.  Back to cited text no. 9
    
10.
Henry BM, Benoit SW, Santos de Oliveira MH, Hsieh WC, Benoit J, Ballout RA, et al. Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): A pooled analysis and review. Clin Biochem 2020; 81: 1-8.  Back to cited text no. 10
    
11.
Slater A, Shann F, Pearson G. PIM2: a revised version of the pediatric index of mortality. Intensive Care Med 2003; 29(2): 278-285.  Back to cited text no. 11
    
12.
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(8): 801-810.  Back to cited text no. 12
    
13.
Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a Pediatric Sequential Organ Failure Assessment Score and evaluation of the Sepsis-3 definitions in critically ill children. JAMA Pediatr 2017; 171(10): e17235.  Back to cited text no. 13
    
14.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41(2): 580-637.  Back to cited text no. 14
    
15.
Biron BM, Ayala A, Lomas-Neira JL. Biomarkers for sepsis: What is and what might be? Biomark Insights 2015; 10s4: 7-17.  Back to cited text no. 15
    
16.
Khan AA, Allemailem KS, Alhumaydhi FA, Gowder SJT, Rahmani AH. The biochemical and clinical perspectives of lactate dehydrogenase: An enzyme of active metabolism. Endocr Metab Immune Disord Drug Targets 2020; 20(6): 855-868.  Back to cited text no. 16
    
17.
Ozkiraz S, Gokmen Z, Boke SB, Kilicdag H, Ozel D, Sert A. Lactate and lactate dehydrogenase in predicting the severity of transient tachypnea of the newborn. J Matern Fetal Neonatal Med 2013; 26(12): 1245-1248.  Back to cited text no. 17
    
18.
Karlsson M, Dung K, Thi TL, Borgström E, Jonstam K, Kasström, et al. Lactate dehydrogenase as an indicator of severe illness in neonatal intensive care patients: a longitudinal cohort study. Acta Paediatr 2012; 101(12): 1225-1231.  Back to cited text no. 18
    
19.
Wasserman A, Shnell M, Boursi B. Prognostic significance of serum uric acid in patients admitted to the department of medicine. AMJ Med Sci 2010; 339(1): 5-21.  Back to cited text no. 19
    
20.
Hendya RM, Elawadyb MA, Abd EL Kareemc HM. Role of lactate dehydrogenase and other biomarkers inpredicting prognosis of community-acquired pneumonia. Egypt J of Bronchol 2020; 13(4): 539-544.  Back to cited text no. 20
    
21.
Jeong JE, Soh JE, Kwak JH, Jung HL, Shim JW, Kim DS, et al. Increased procalcitonin level is a risk factor for prolonged fever in children with Mycoplasma pneumonia. Korean J Pediatr 2018; 61(8): 258-263.  Back to cited text no. 21
    
22.
Butt AA, Michaels S, Kissinger P. The association of serum lactate dehydrogenase level with selected opportunistic infections and HIV progression. Int J Infect Dis 2002; 6(3): 178-181.  Back to cited text no. 22
    
23.
Deng C, Li Y, Li Y. Systemic review: the accuracy of lactic dehydrogenase in the diagnosis of pneumocystis pneumonia. Zhonghua Wei Zhong Bing Ji Jiu Yi 2018; 30(4): 322-326.  Back to cited text no. 23
    
24.
Helliksson F, Wernerman J, Wiklund L, Rosell J, Karlsson M. The combined use of three widely available biochemical markers as predictor of organ failurein critically ill patients. Scand J Clin Lab Invest 2016: 76(6): 479-485.  Back to cited text no. 24
    
25.
García-Gigorro R, Sáez-de la Fuente I, Marín Mateos H, Andrés-Esteban EM, Sanchez-Izquierdo JA, Montejo-González JC. Utility of SOFA and -SOFA scores for predicting outcome in critically ill patients from the emergency department. Eur J Emerg Med 2019; 26(4): 309-310.  Back to cited text no. 25
    
26.
Farah R, Makhoul N. Usefullness of various inflammatory markers to differentiate pulmonary edema from pneumonia. Isr Med Assoc J 2011: 13(4): 225-229.  Back to cited text no. 26
    
27.
Anand M, Radhakrishnan A, Rajendiran C, Kanagasabai V. Serum lactate dehydrogenase and C reactive protein levels in sepsis and itscorrelation with APACHE-II score. [Online] Available from: http://repository-tnmgrmu.ac.in/6754/1/200100112anand.pdf. [Accessed on 20 January 2021].  Back to cited text no. 27
    
28.
Chkhaidze MG, Kheladze ZS, Pruidze DR, Abelashvili DI, Gvetadze PR. Comparison of PIM and SOFA scoring systems for mortality risk prognosis in critically ill children with sepsis. Georgian Med News 2006; (131): 66-68.  Back to cited text no. 28
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
1. Introduction
2. Patients and ...
3. Results
4. Discussion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed334    
    Printed0    
    Emailed0    
    PDF Downloaded53    
    Comments [Add]    

Recommend this journal