Serum lactate as predictor and diagnostic biomarker of plasma leakage in adult dengue patients

Main Article Content

Rika Bur
Suhendro Suwarto
Widayat Djoko Santoso
Kuntjoro Harimurti

Abstract

Background
Dengue fever (DF) and dengue hemorrhagic fever (DHF) are differentiated by the occurrence in DHF of plasma leakage into the interstitial space as shown by pleural and peritoneal effusion, hemoconcentration, and intravascular hypovolemia. Perfusion dysfunction causes anaerobic metabolism, which leads to increased serum lactate. This study was to determine serum lactate as prognostic predictor and diagnostic biomarker of plasma leakage in adult dengue patients.

Methods
A cross-sectional retrospective cohort study was conducted on 57 adult dengue patients hospitalized in the internal medicine ward of Cipto Mangunkusumo Hospital and Persahabatan Hospital in Jakarta. Serum lactate was examined to determine its mean difference between DF and DHF. The data was analyzed by independent t-test and the cut-off points were identified for presence as well as absence of plasma leakage, then the receiver operating characteristics (ROC) curve was used to determine sensitivity and specificity.

Results
Mean serum lactate was significantly higher in DHF than in DF. From the ROC curve, the cut-off point for serum lactate as prognostic predictor on day 3 of fever was ³2.65 mmol/L with AUC of 0.626 (95% CI 0.480-0.772; p=0.108). The cut-off point for diagnostic biomarker of plasma leakage on day 5 of fever was 2.55 mmol/L with sensitivity 66.6%, specificity 54.2%, and AUC 0.668 (95% CI 0.550-0.826; p=0.016).

Conclusion
There was a significant difference in serum lactate between DF and DHF. In the critical phase, serum lactate of 2.55 mmol/L could be used as plasma leakage diagnostic marker of low accuracy.

Article Details

How to Cite
Bur, R., Suwarto, S., Santoso, W. D., & Harimurti, K. (2016). Serum lactate as predictor and diagnostic biomarker of plasma leakage in adult dengue patients. Universa Medicina, 35(3), 213–221. https://doi.org/10.18051/UnivMed.2016.v35.213-221
Section
Original Articles
Author Biographies

Rika Bur, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

Suhendro Suwarto, Division of Tropical and Infectious Disease, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

Division of Tropical and Infectious Disease, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

Widayat Djoko Santoso, Division of Tropical and Infectious Disease, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

Division of Tropical and Infectious Disease, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

Kuntjoro Harimurti, Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia Clinical Epidemiology and Evidence-based Medicine (CEEBM) Unit, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

Department of Internal Medicine, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

 

Clinical Epidemiology and Evidence-based Medicine (CEEBM) Unit, Faculty of Medicine, University of Indonesia-RSUPN Cipto Mangunkusumo, Jakarta, Indonesia

References

Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature 2013; 496:504-7.

Kementerian Kesehatan Republik Indonesia. Demam berdarah dengue. Jakarta: Pusat Data dan Surveilans Epidemiologi Kementerian Kesehatan Republik Indonesia;2010.

Kementerian Kesehatan Republik Indonesia. Profil kesehatan indonesia 2013. Jakarta: Kementerian Kesehatan Republik Indonesia; 2014.

Srikiatkhachorn A. Plasma leakage in dengue haemorrhagic fever. Thromb Haemost 2009;102: 1042-9.

Simmons CP, Farrar JJ, Chau NV, et al. Dengue. N Engl J Med 2012;366:1423-32.

Lee YR, Liu MT, Lei HY, et al. MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells. J Gen Virol 2006;87:3623-30.

Yacoub S, Mongkolsapaya J, Screaton G. The pathogenesis of dengue. Curr Opin Infect Dis 2013;26:284-9.

Santosa D, Alwi EH, Idjradinata PS. Validitas kadar laktat darah dalam mendeteksi kebocoran plasma pada infeksi virus dengue anak. Majalah Kedokteran Indonesia 2011;61:58-62.

World Health Organization. Dengue: guidelines for diagnosis, treatment, prevention and control. Geneva: World Health Organization;2009.

Villar-Centeno LA, Diaz-Quijano FA, Martinez-Vega RA. Biochemical alterations as markers of dengue hemorrhagic fever. Am J Trop Med Hyg 2008;78:370-4.

Potts JA, Thomas SJ, Srikiatkhachorn A, et al. Classification of dengue illness based on readily available laboratory data. Am J Trop Med Hyg 2010;83:781-8.

Kuo MC, Lu PL, Chang JM, et al. Impact of renal failure on the outcome of dengue viral infection. Clin J Am Soc Nephrol 2008;3:1350-6.

Fuller BM, Dellinger RP. Lactate as a hemodynamic marker in the critically ill. Curr Opin Crit Care 2012;18:267-72.

Krishna U, Joshi SP, Modh M. An evaluation of serial blood lactate measurement as an early predictor of shock and its outcome in patients of trauma or sepsis. Indian J Crit Care Med 2009; 13:66-73.

Puspanjono MT, Latief A, Tumbelaka AR, et al. Comparison of serial blood lactate level between dengue shock syndrome and dengue hemorrhagic fever (evaluation of prognostic value). Paediatrica Indonesiana 2007;47:151.

Sirikutt P, Kalayanarooj S. Serum lactate and lactate dehydrogenase as parameters for the prediction of dengue severity. J Med Assoc Thai 2014;97 Suppl 6:S220-31.

Halstead SB. The World Health Organization definition of dengue hemorrhagic fever is inadequate for clinical and epidemiological purposes. In: Pascol G, Hoffman SL, editors. Dengue tropical medicine: science and practice. 5th vol. London: Imperial College Press; 2008.p. 427-31.

Thanachartwet V, Wattanathum A, Oer-areemitr N, et al. Diagnostic accuracy of peripheral venous lactate and the 2009 WHO warning signs for identifying severe dengue in Thai adults: a prospective observational study. BMC Infect Dis 2016;16:46. doi: 10.1186/s12879-016-1386-5.

Thanachartwet V, Desakorn V, Sahassananda D, et al. Serum procalcitonin and peripheral venous lactate for predicting dengue shock and/or organ failure: a prospective observational study. PLoS Negl Trop Dis 2016;10: e0004961. doi:10.1371/journal.pntd.0004961.

Madiyono B, Moeslichan SMZ, Sastroasmoro S, et al. Perkiraan besar sampel. In: Sastroasmoro S, Ismael S, editors. Dasar-dasar metodologi penelitian klinis. 5th ed. Jakarta: Sagung Seto; 2014.p.352-87.

Hajian-Tilaki K. Sample size estimation in diagnostic test studies of biomedical informatics. J Biomed Informatics 2014;48:193-204.

Nainggolan L. Pengembangan sistem skor sebagai prediktor kebocoran plasma pada demam berdarah dengue: peran sTNFR-1, VEGF, sVE- CADHERIN dalam patofisiologi kebocoran plasma [Disertasi]. Jakarta: Universitas Indonesia;2012.

Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580-637.

Huy NT, Van Giang T, Thuy DHD, et al. Factors associated with dengue shock syndrome: a systematic review and meta-analysis. PLoS Negl Trop Dis 2013;7:e2412. doi: 10.1371/journal. pntd.

Thanachartwet V, Oer-Areemitr N, Chamnanchanunt S, et al. Identification of clinical factors associated with severe dengue among Thai adults: a prospective study. BMC Infect Dis 2015;15:420.

Sterling SA, Puskarich MA, Jones AE. The effect of liver disease on lactate normalization in severe sepsis and septic shock: a cohort study. Clin Exp Emerg Med 2015;2:197-202.

Premaratna R, Ragupathy A, Miththinda JK, et al. Timing, predictors, and progress of third space fluid accumulation during preliminary phase fluid resuscitation in adult patients with dengue. Int J Infect Dis 2013;17:e505-9.

Bakker J, Nijsten MWN, Jansen TC. Clinical use of lactate monitoring in critically ill patients. Ann Intensive Care 2013;3:12.