Effect of Hypertonic Sodium Lactate on sVCAM-1 Level as Surrogate Marker of Endothelial Capillary Leakage in Pediatric Dengue Shock Syndrome Patients (DSS)
Summary
Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are among the leading causes of pediatric hospitalization in Asia.Mortality rates range from 1% at centres experienced in fluid resuscitation, to upto 44% in established shock.The mainstay of DSS treatment is prompt, vigorous fluid resuscitation with isotonic crystalloid solutions, followed by plasma or colloid solutions for profound or continuing shock. However, this administration is often associated with fluid overload and induces edema in these patients. Hence, we planned a parallel, randomized controlled trial comparing the efficacy and safety of solution containing half molar sodium lactate (Totilac™) with standard treatment(isotonic crystalloid Ringer's Lactate) in pediatric Dengue Shock Syndrome patients, using plasma soluble Vascular Cell Adhesion Molecule(sVCAM-1) levels as an indicator. Hypertonic solutions restore hemodynamic status rapidly with increased cardiac performance and improved tissue perfusion. This is obtained with much smaller volumes.We plan to assess the efficacy and safety of hypertonic sodium lactate in resuscitation of DHF/DSS patients.
Timeline
- Start
- 2008-05
- Primary completion
- 2009-04
- Completion
- 2009-12
Publications
- Background Ampaiwan Chuansumrit, MD & Kanchana Tangnararatchakit, MD, Pathophysiology and management of dengue hemorrhagic fever, Journal Compilation, 2006. Transfusion Alternatives in Transfusion Medicine 8 (Suppl. 1), 3-11
- Background Murgue B, Cassar O, Deparis X. Plasma concentrations of sVCAM-1 and severity of dengue infections. J Med Virol. 2001 Sep;65(1):97-104.
- Background Wills BA, Nguyen MD, Ha TL, Dong TH, Tran TN, Le TT, Tran VD, Nguyen TH, Nguyen VC, Stepniewska K, White NJ, Farrar JJ. Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med. 2005 Sep 1;353(9):877-89. doi: 10.1056/NEJMoa044057.
- Background Bethell DB, Gamble J, Pham PL, Nguyen MD, Tran TH, Ha TH, Tran TN, Dong TH, Gartside IB, White NJ, Day NP. Noninvasive measurement of microvascular leakage in patients with dengue hemorrhagic fever. Clin Infect Dis. 2001 Jan 15;32(2):243-53. doi: 10.1086/318453. Epub 2001 Jan 15.
- Background Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials. BMJ. 1998 Mar 28;316(7136):961-4. doi: 10.1136/bmj.316.7136.961.
- Background Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev. 1998 Jul;11(3):480-96. doi: 10.1128/CMR.11.3.480.
- Background Jiang G, Klein JD, O'Neill WC. Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism. Am J Physiol Cell Physiol. 2001 Dec;281(6):C1948-53. doi: 10.1152/ajpcell.2001.281.6.C1948.
- Background Boldt J. New light on intravascular volume replacement regimens: what did we learn from the past three years? Anesth Analg. 2003 Dec;97(6):1595-1604. doi: 10.1213/01.ANE.0000089961.15975.78.
- Background Leverve XM, Boon C, Hakim T, Anwar M, Siregar E, Mustafa I. Half-molar sodium-lactate solution has a beneficial effect in patients after coronary artery bypass grafting. Intensive Care Med. 2008 Oct;34(10):1796-803. doi: 10.1007/s00134-008-1165-x. Epub 2008 Jun 18.
- Background Leverve XM, Mustafa I. Lactate: A key metabolite in the intercellular metabolic interplay. Crit Care. 2002 Aug;6(4):284-5. doi: 10.1186/cc1509. Epub 2002 Jul 8.
- Background Mustafa I, Leverve XM. Metabolic and hemodynamic effects of hypertonic solutions: sodium-lactate versus sodium chloride infusion in postoperative patients. Shock. 2002 Oct;18(4):306-10. doi: 10.1097/00024382-200210000-00003.
- Background Valero N, Espina LM, Anez G, Torres E, Mosquera JA. Short report: increased level of serum nitric oxide in patients with dengue. Am J Trop Med Hyg. 2002 Jun;66(6):762-4. doi: 10.4269/ajtmh.2002.66.762.
- Background Ngo NT, Cao XT, Kneen R, Wills B, Nguyen VM, Nguyen TQ, Chu VT, Nguyen TT, Simpson JA, Solomon T, White NJ, Farrar J. Acute management of dengue shock syndrome: a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis. 2001 Jan 15;32(2):204-13. doi: 10.1086/318479. Epub 2001 Jan 15.
- Background O'Neill WC. Physiological significance of volume-regulatory transporters. Am J Physiol. 1999 May;276(5):C995-C1011. doi: 10.1152/ajpcell.1999.276.5.C995.
- Background Avirutnan P, Malasit P, Seliger B, Bhakdi S, Husmann M. Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis. J Immunol. 1998 Dec 1;161(11):6338-46.
- Background Rocha-e-Silva M, Poli de Figueiredo LF. Small volume hypertonic resuscitation of circulatory shock. Clinics (Sao Paulo). 2005 Apr;60(2):159-72. doi: 10.1590/s1807-59322005000200013. Epub 2005 Apr 26.
- Background Lawn SD, Tilley R, Lloyd G, Finlayson C, Tolley H, Newman P, Rice P, Harrison TS. Dengue hemorrhagic fever with fulminant hepatic failure in an immigrant returning to Bangladesh. Clin Infect Dis. 2003 Jul 1;37(1):e1-4. doi: 10.1086/375601. Epub 2003 Jun 25.
- Background Svensen CH. Hypertonic Solutions: An Update. ITACCS Clinical Issues. 2002, 6 -12
- Background Tan TS, Tan KH, Ng HP, Loh MW. The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis: an in vitro assessment using thromboelastography. Anaesthesia. 2002 Jul;57(7):644-8. doi: 10.1046/j.1365-2044.2002.02603.x.
- Background World Health Organization, Dengue, Dengue Haemorrhagic Fever and Dengue Shock Syndrome in the Context of the Integrated Management of Childhood Illness, 2005
- Somasetia DH, Setiati TE, Sjahrodji AM, Idjradinata PS, Setiabudi D, Roth H, Ichai C, Fontaine E, Leverve XM. Early resuscitation of dengue shock syndrome in children with hyperosmolar sodium-lactate: a randomized single-blind clinical trial of efficacy and safety. Crit Care. 2014 Sep 5;18(5):466. doi: 10.1186/s13054-014-0466-4.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Hypertonic lactate | Unknown | 1 unknown | — |
| Comparator | Ringer's Lactate | Other / unclassified | 3 unknown | — |