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Dengue Hemorrhagic Fever Management

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Dengue Hemorrhagic Fever Management

Dengue Hemorrhagic Fever Management

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    Dengue Hemorrhagic Fever Management Dengue Hemorrhagic Fever Management Presentation Transcript

    •  
      • Recognition of DengueFever/Dengue Haemorrhagic Fever (DF/DHF)
      • Dengue Fever - an acute febrile illness of 2-7 days duration (sometimes with two peaks) with
      • two or more of the following manifestations:
          • headache
          • Retro-orbital pain
          • myalgia / arthralgia
          • rash
          • leukopenia
      Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999
      • Dengue Hemorrhagic Fever (DHF)
      • - a severe case of dengue with hemorrhagic tendency evidenced by:
        • Positive tourniquet test
        • Petechiae, ecchymosis or purpura
        • Bleeding from mucosa (epistaxis or bleeding from gums), injection sites or other sites
      Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999
    • Tourniquet Test
      • AKA: Rumpel-Leede Capillary-Fragility Test determines capillary fragility.
      • bp cuff is inflated to a point between the systolic and diastolic bp for 5min.
      • (+): 10 or more petechiae per square inch. In DHF the test usually gives a definite positive result with 20 petechiae or more
        • Hematemesis or melena
        • Thrombocytopenia ( ≤ 100,000/cu.mm )
        • Evidence of plasma leakage manifested by:
          • – A >20% rise in hematocrit for age and sex
          • – A >20% drop in hematocrit following treatment
          • with fluids as compared to baseline
          • – Signs of plasma leakage (pleural effusion,
          • ascites or hypoproteinemia )
      Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999
      • Dengue Shock Syndrome (DSS)
      • - All the above criteria of DHF plus signs of circulatory failure manifested by the ff:
        • rapid and weak pulse
        • narrow pulse pressure (</= to 20mm Hg)
        • hypotension for age
        • cold and clammy skin
        • Restlessness
        •  or absent urine
      Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999
    • Grading the Severity of Dengue Infection Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999 DF / DHF Grade Symptoms Labs DF Fever with two or more of the ff: headache, retro-orbital pain, myalgia, arthralgia Leukopenia Thrombocytopenia < 100,000 No evidence of plasma loss DHF I Above signs plus positive tourniquet test Thrombocytopenia <100,000 Hct rise >20% DHF II Above signs plus spontaneous bleeding Thrombocytopenia <100,000 Hct rise >20% DHF III Above signs plus circulatory failure (weak pulse, hypotension restlessness) Thrombocytopenia <100,000 Hct rise >20% DHF IV Profound shock with undetectable blood pressure and pulse Thrombocytopenia <100,000 Hct rise >20%
    • Criteria For Hospitalization
      • General Condition
      • Continuous fever ≥ 3 days
      • Lethargy
      • Restlessness
      • Generalized Flushing
      • Excessive tiredness
      • Poor appetite
      • Dehydration
      • Unable to tolerate orally / vomiting
      • Diarrhea / frequent loose stools
      • Abdominal Discomfort
      • Right hypochondrium/epigastric pain
      • Tender hepatomegaly
      • Plasma leakage manifested by:
      • Rapid rising hematocrit
      • Hematocrit =/ ≥ 20% of baseline
      • Pleural Effusion, ascites
    • Criteria For Hospitalization
      • Hemorrhagic manifestations
      • (+) tourniquet test
      • Petechiae, ecchymoses, purpura
      • Spontaneous mucosal bleeding
      • Hematemesis, melena,
      • hematochezia, thrombocytopenia
      • Patients w/ bleeding regardless of platelet count
      • W/out bleeding but platelet count is on rapid down trend
      • Platelet count < 100,000/mm 3
      • Evidence of circulatory
      • failure/shock as manifested
      • by:
      • Rapid & weak pulse
      • Diminished peripheral pulses
      • Narrowing of pulse pressure
      • Hypotension for age
      • Cool, mottled or pale skin
      • Oliguria
      • Tachypnea ( due to metabolic
      • acidosis
      • Changes in mental status, lethargy,
      • restlessness
    • GENERAL MANAGEMENT OF DENGUE
      • 1.) Rest
      • 2.) Antipyretic
      • Do not give Aspirin or Ibuprofen
      • 3.) Oral rehydration therapy
      • 4.) Food according to appetite
      Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999
    • Treatment Of Dengue with hemorrhage & shock
      • 1.) Supportive measures
      • 2.) Fluid Resuscitation
            • Crystalloids vs Colloids
      • 3.) Blood Component Therapy
            • Packed Red Blood Cells
            • Fresh Frozen Plasma / Cryoprecipitate
            • Platelet concentrate
        • 4.) Oxygen therapy
        • 5.) Others
            • Inotropes - Dopamine,Dobutamine,
            • Epinephrine, Norepinephrine,Milrinone
      • CRYSTALLOIDS
      • vs.
      • COLLOIDS
      FLUID RESUSCITATION
    • Fluids Required for Intravenous Therapy
      • Crystalloids
      • Plain/ 5% dextrose in isotonic normal saline solution (NSS)
      • Plain/5%dextrose in half-strength normal saline solution (O.45 %NaCl)
      • Plain/5% dextrose in lactated Ringer’s solution (LRS)
      Guidelines for Treatment of DF/ DHF in Small Hospitals WHO, New Delhi, 1999
    • Fluids Required for Intravenous Therapy
      • Colloids
      • Dextran
      • Hydroxyethyl starch
      • Gelatin solutions
      • Plasma
      • Albumin
      • Theoretically, colloid solutions offer advantages over crystalloid solutions for emergency resuscitation:
      • 1.) Immediate distribution of colloids within the intra vascular compartment
      • 2.) Colloid molecules increase plasma oncotic pressure thereby altering the balance of fluid flux across the endothelium and drawing fluid back into the intra vascular compartment
    • DRAWBACK IN THE USE OF COLLOIDS:
      • Colloids may leak into the interstitium and exert a reverse osmotic effect, drawing out intravascular fluid & worsening the shock
      • Risk in developing acute renal failure
      • Potential for allergic reactions
      • Adverse effects on blood coagulation
      • Expensive & not readily available
    • Advantages of Crystalloids:
      • Cheap & Readily available
      • Generally safe
      • Reaction free
    • Studies on the Different Fluid Regimen in the Initial Resuscitation of DSS
      • 1.) Fluid Replacement in DSS: A Randomized, Double Blind Comparison
      • of the Four Intravenous Fluid Regimen
      • by: Dung NM, Day NPJ, et al
      • Clinical Infectious Disease, 1999: 29: 787 – 795
      • 2.) Acute Management of DSS: A Randomized, Double Blind Comparison
      • of Four Intravenous Fluid Regimens in the First Hour
      • by: Nhan NT, Phuong CX, et al
      • Clinical Infectious Disease 2001: 32: 204 – 213
      • 3.) Comparison of Three Fluid Solutions for Resuscitation in DSS
      • by: Wills B et al
      • New England Journal Of Medicine, Sept 2005: 353, No 9: 877-889
      • The study aims to compare the efficacy of 4 fluid regimens in the initial resuscitation of DSS in children:
              • Dextran
              • Gelatin solution
              • Lactated Ringers
              • Normal Saline
      Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213
    • Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213
      • 230 Vietnamese children with DSS admitted at the ICU of Dong Nai Pediatric Hospital, Bien Hoa, Dong Nai Province, Southern Vietnam
      • Sept 1996 – Sept 1997 were included in the study
    • Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213
      • Results
      • Ringers Lactate performed the least well due to the following reasons :
        • Recovery times were longer
        • Initial therapy was considered a failure
        • Dextran was more likely to be required for
        • treatment of the initial episode of shock
        • Has greater # of children w/ profound shock
      • O.9% saline may be the crystalloid fluid of choice for resuscitation of the majority of patients with DSS
      Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213
      • The plasma volume – expanding capacity of the 2 crystalloid solutions is related to its sodium concentration:
          • Normal Saline – 154 m M
          • Lactated Ringers – 130 m M
      Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213
      • Conclusion
      • The study is unable to demonstrate a clear benefit of any 1 of the 4 fluids in the treatment of children with DHF 111
      • For the majority of patients w/ less severe disease, the type of fluid used for resuscitation may not matter
      • In more severely-ill patients , early treatment with colloids improve outcome
      Acute Management of DSS: A Randomized, Double blind Comparison of Four Intravenous Fluid Regimens in the First Hour by: Nhan NT, Phuong CX, et al Clinical Infectious Disease 2001: 32: 204 – 213
      • 383 Vietnamese children with moderately severe shock were randomly assigned to receive Ringer's lactate, 6 % dextran 70 (a colloid), or 6 % hydroxyethyl starch (a colloid)
      • 129 Vietnamese children with severe shock were randomly assigned to receive one of the colloids 6 % dextran 70 or 6 % hydroxyethyl starch
      Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353, No 9:877-889
    • Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889
      • Results
      • No significant difference among the fluids in terms of overall proportion of children requiring rescue colloid in either severity group
      • Children in group 1 who received Ringer's lactate for primary resuscitation took longer to achieve initial cardiovascular stability than patients receiving either of the colloids
    • Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353, No 9:877-889
      • Results
      • The time to final cardiovascular stability was not different among the fluid-treatment group
      • No difference in either severity group in the requirement for colloid subsequent to the initial episode of shock, in the volume of rescue colloid or total parenteral fluid administered, in the final recovery times or in the number of days in the hospital
    • Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889
      • Results
      • No significant differences in any adverse effects of the various fluid treatments except in the incidence of allergic type reactions
      • No difference among the fluid treatment groups in the development of new bleeding manifestations, clinical fluid overload, objective measures of the over-all severity of vascular leakage or the use of furosemide
    • Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889
      • Conclusion:
      • Most children with dengue shock syndrome respond well to judicious treatment with isotonic crystalloid solutions
      • The cheapest and safest choice, Ringer's lactate , is as effective as either of the colloids for initial resuscitation of children with moderately severe shock
      • Early intervention with colloid solutions is not indicated
    • Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353,No 9:877-889
      • Conclusion:
      • The fluid regimen of Ringer's lactate at 25 ml / kg over a period of two hours is now supported by strong prospective evidence and should be recommended for children with moderately severe shock
    • Comparison of Three Fluid Solutions for Resuscitation in DSS by: Wills B, Nguyen M. Dung, et al New England Journal Of Medicine, Sept 2005: 353, No 9: 877-889
      • Conclusion:
      • For those with severe shock , the situation is less clear-cut, and clinicians must continue to rely on personal experience, familiarity with particular products, local availability, and cost.
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • Compared the following outcomes of children w/ DSS
      • using the standard WHO therapy vs instituted
      • protocol for aggressive management:
          • duration of ventilation
          • ICU stay
          • incidence of ARDS
          • ICU & hospital mortality
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • 114 patients admitted at the Kanchi Kamakoti Childs Trust Hospital in South India between July 1997 and December 1999 received WHO standard therapy
      • 96 patients admitted at the Kanchi Kamakoti Childs Trust Hospital in South India between January 2000 and December 2001 received the instituted protocol for aggressive management
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • The 1st group ( W Group ):
      • Included patients who received standard WHO-prescribed therapy
      • Received volume resuscitation w/ isotonic fluids such as LR or Normal saline followed by colloids
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • The 2nd group or Treatment Protocol (P Group):
      • Included patients who received other therapies in addition to the standard WHO-prescribed therapy
      • Additional intervention employed in the P group:
      • Use of Controlled Fluid Removal Therapy in patients
      • w/ deterioration in respiratory function using :
      • 1.) low dose Furosemide infusion ( FI )
      • 2.) Peritoneal dialysis ( PD )
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • Controlled fluid removal therapy employed in the P group was used in selected patients who developed substantial deterioration in respiratory function:
          • Tachypnea
          • Grunting
          • Increased oxygen requirement
          • Need for assisted ventilation
          • Generalized pulmonary edema
          • Serum albumin of <3.0 g% after restoration of normovolemia
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • 1.) Low dose Furosemide infusion ( FI )
      • Preferred treatment in hemodynamically stable patients
      • Used at 0.05-0.4 mg/kg/hr and titrated to maintain a urine output of 2-5 mL/kg/hr
      • In the event of systemic hypoperfusion, the rate of fluid resuscitation was increased and FI was temporarily withheld
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • FAILURE OF FUROSEMIDE INFUSION:
      • IF URINE OUTPUT DID NOT INCREASE TO 2 ML/KG/ HR DESPITE A MAXIMUM DOSE 0.4MG/KG/HR
      • IF THE PATIENT EXPERIENCED FREQUENT EPISODES OF HEMODYNAMIC INSTABILITY
      • ACUTE INTERMITTENT
      • PERITONEAL DIALYSIS
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419
      • Results:
      • The duration of ventilation & mean length of ICU stay were significantly longer in the P group
      • The need for ventilation and incidence of ARDS were not significantly different in the 2 groups
    • Aggressive Management of Dengue Shock Syndrome May Decrease Mortality Rate : A Suggested Protocol by: Ranjit Suchitra, Kissoon Niranjan, Jayakumar Indira Pediatric Critical Care Medicine, Vol 6 (4), July 2005, 412 - 419 W group P group Mean time of death (days) 1.4 4.5 Mortality Rate 22% 7% # of patients dying within 24 hours of admission to the ICU 13 out of 19 2 out 6 Causes of death 7 - Refractory shock 10 - MODS (ARDS and DIC) 2 - Fulminant hepatic failure 5 – Refractory shock 1 - Fulminant hepatic failure
      • Blood Component Therapy
    • Indications For Blood Products in Dengue Infection
      • 1. ) PRBC - for volume depletion from massive bleeding
      • 2.) Platelet concentrate – generally avoided unless:
          • significant / massive bleeding regardless of PC
          • PC < 10,000/mm 3 with impending /established CNS
          • bleed or continuous bleeding from a pre – existing
          • peptic ulcer
      • 3.) FFP -for patients where coagulopathy causes massive
      • bleeding
    • Protrombin & Partial Thromboplastin Time as a Predictor of Bleeding in Patients w/ patients with DHF Chua MN, Molanida R, et al South East Asian Journal Tropical Medicine & Public Health,1993; 24(1): 141-143
    • Protrombin & Partial Thromboplastin Time as a Predictor of Bleeding in Patients w/ patients with DHF Chua MN, Molanida R, et al South East Asian Journal Tropical Medicine & Public Health,1993; 24(1): 141-143
      • Conclusion:
        • PTT can be an index in predicting bleeding in DHF. The tendency to bleed is greater with prolongation of > 30 seconds
        • Platelet count can be a predictor of mortality, with death six times greater among those platelet count < 50,000/microliters than those whose platelet count was > 50,000/microliters
        • PT can also predict bleeding in patients with DHF
    • Preventive transfusion in Dengue shock syndrome- is it necessary? Lum LC, Abdel-Latif Mel A, Goh AY. Chan PW, Lam SK (2003). J Pediatr, 143(5), Sep, pp 682-4
      • Preventive transfusion with platelet concentrates and FFP a in non-bleeding or fluid responsive DHF/DSS has not been shown to sustain the increase in platelet counts, prothrombin time or partial prothrombin time (PT/PPT)
      • This practice has been shown to increase the incidence of fluid overload and pulmonary edema, and puts the patient at risk of blood-borne infections from multiple donors
              
    • Preventive transfusion in Dengue shock syndrome- is it necessary? Lum LC, Abdel-Latif Mel A, Goh AY. Chan PW, Lam SK (2003). J Pediatr, 143(5), Sep, pp 682-4
      • The liberal use of blood products in the treatment of DHF / DSS creates a real
      • danger to the patient in addition to the
      • unnecessary cost & an incorrect focus in
      • the treatment
      • The practice was stopped in 1997
    • Role of platelet transfusion in dengue hemorrhagic fever Kabra SK, Jain Y,Madhulika et al Indian Pediatr 1998; 35 : 452-454.
      • Preventive transfusion with platelets
      • & FFP are not necessary for treating
      • DHF/DSS
    • Thrombocytopenia & Platelet transfusion in DHF & DSS Alex Chairulfatah, Setiabudi D, et al Institute of Tropical Medicine, Belgium, 1995; 75 (4) : 291-295
      • To evaluate the effect of platelet transfusions to prevent bleeding in DHF / DSS patients
      • All patients admitted with DHF / DSS between August 1995 – March 1996 in 4 major hospitals in Bandung Indonesia were included in the study
    • Thrombocytopenia & Platelet transfusion in DHF & DSS Alex Chairulfatah, Setiabudi D, et al Institute of Tropical Medicine, Belgium, 1995; 75 (4) : 291-295
      • Conclusion
      • In most DHF / DSS cases, platelet transfusions do not influence the incidence of severe bleeding
      • There are no prospective studies and consensus on platelet transfusion based on low platelet count w/ or w/out bleeding in dengue infection
      • There are no randomised prospective studies to show that administration of FFP or platelet concentrates have improved the outcome of DHF / DSS in adults
      Clinical Practice Guidelines, Dengue Infection in Adults Dengue Consensus 2003, Academy of Medicine Malaysia Ministry of Health
    • RECOMBINANT ACTIVATED FACTOR ( rFV11a )
    • Recombinant Activated Factor VII ( rFVIIa )
      • Provide effective hemostasis in severe uncontrolled bleeding in patients without preexisting coagulopathy undergoing various major surgeries or in patients receiving warfarin for thromboprophylaxis
      • Used in controlling life-threatening bleeding in Dengue Shock Syndrome
    • Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555
      • Objective:
      • To evaluate the efficacy and safety of Recombinant Activated Factor VII (rFVIIa) in children aged < 18 years old with grade II or grade III Dengue hemorrhagic fever (DHF) who required blood component therapy for controlling bleeding episodes
    • Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555
      • Patients who had been admitted or referred to the following
      • hospitals from July 2001 to December 2002 were included:
      • Ramathibodi Hospital (Bangkok, Thailand)
      • Buddhachinaraj Hospital (Phitsanuloke, Thailand)
      • Supprasithprasong Hospital (Ubonrajchathani, Thailand)
      • University of Santo Tomas (Manila, Philippines)
      • Research Institute for Tropical Medicine (Muntinlupa
      • City, Philippines)
    • Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555
      • The 1st dose of rFVIIa ( NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) or placebo at 100 ug/kg body weight was given by intravenous injection
      • When the bleeding was not effectively controlled, a 2nd dose (100 ug/kg) was given 30 min after the first dose
    • Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555
      • Conclusion:
      • rFVIIa appears to be useful as an adjunctive treatment to blood component replacement in controlling active bleeding episodes in children with grade II or grade III DHF when platelet concentrates are not available
    • Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555
      • The study could not show the effect of rFVIIa on the reduction of RBC transfusion requirement, possibly due to the small number of patients and non-optimized dose regimen of rFVIIa
    • Control of bleeding in children with Dengue Hemorrhagic Fever using Recombinant activated Factor VII: A Randomized, Double-blind, Placebo-controlled Study Ampaiwan Chuansumrita, Somporn Wangruangsatidb, et al Blood Coagulation and Fibrinolysis 2005, Vol 16 No 8, 549–555
      • Concerning safety, rFVIIa does not appear to aggravate clinical condition of patients with DHF grade II / III to full-blown DIC
    • The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome Ampaiwan Chuansumrita, Kanchana Tangnararatchakita, et al Blood Coagulation and Fibrinolysis 2004, 15:335–342
      • To report the use of recombinant activated factor VII (rFVIIa) in controlling life-threatening bleeding episodes in patients with grades III
      • and IV DHF
    • The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome Ampaiwan Chuansumrita, Kanchana Tangnararatchakita, et al Blood Coagulation and Fibrinolysis 2004, 15:335–342
      • The rFVIIa (NovoSeven; Novo Nordisk A/S, Bagsvaerd, Denmark) of 100 g/kg was given as a single dose or repeated doses at intervals of 4 h according to the bleeding symptoms
    • The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome Ampaiwan Chuansumrita, Kanchana Tangnararatchakita, et al Blood Coagulation and Fibrinolysis 2004, 15:335–342
      • Conclusion
      • The use of rFVIIa, given as bolus injection of 100 g/kg as a single dose or repeated doses at intervals of 4 h for one to three doses seems to be effective in restoring hemostasis to control life-threatening bleeding in a limited series of patients with DSS
    • OXYGEN THERAPY
      • Role of the following in DHF:
      • 1.) Immunoglobulin
      • 2.) Steroids
      • 3.) Dengue Vaccine
    • ROLE OF IV Ig
    • The use of intravenous gammaglobulin in dengue fever, a case report. Ascher DP , Laws HF , Hayes CG . Department of Pediatrics, 13th Air Force Medical Center, Manila, Phil Southeast Asian J Trop Med Public Health. 1989 Dec;20(4):549-54.
      • The documented case of dengue fever with thrombocytopenia was managed with IV IgG. Clinically, and by laboratory parameters, the case dramatically improved after IV IgG administration
      • The use of IV IgG in cases of thrombocytopenia associated with dengue has both theoretical advantages and disadvantages
      • IV IgG may have a role in the management of DHF/DSS
    • ROLE OF STEROIDS
    • Studies on the Role of Steroids in Dengue Shock Syndrome
      • 1.) Failure of High – Dose Methylprednisolone in established DSS: A Placebo-Controlled, Double-Blind Study
      • S Tassniyom, S Vasanawathana, et al Pediatrics, 1993 July; 92 (1): 111-5
      • 2.) Failure of Hydrocortisone to Affect Outcome in DSS
      • Sumarmo, Talogo W., et al Pediatrics 1982, January; 69 (1) 45-9
      • 3.) Hydrocortisone in the Management of DSS
      • Min M, U T, Aye M, et al Southeast Asian Journal of Tropical Public Health. Dec 1975; (4):573-9
    • DENGUE VACCINE
    • Recommendations of the Scientific Working Group on Dengue (2000)
      • Development live-attenuated tetravalent vaccines
        • Guidelines for the safety of dengue vaccines
        • Dengue vaccination may sensitize a recipient so that ensuing dengue infection could result in hemorrhagic fever (Halstead)
    • Is dengue vaccine possible?
      • In principle, an effective vaccine against DV is highly
      • feasible because:
      • it causes only acute infection
      • the virus replication is effectively controlled after a
      • short period of 3 to 7 days of viremia.
      • the individuals who have recovered from DV infection,
      • are immune to rechallenge with the same type but
      • not to other types of DV
      • Developing a vaccine for dengue is a very challenging task because:
          • Dengue infections can be more severe in individuals who have dengue antibodies acquired passively or actively
          • A suitable animal model to evaluate candidate dengue vaccines is not available
    • Dengue Vaccines
      • Conventional vaccines
      • Flavivirus-based recombinant vaccines
      • Intertypic chimeric vaccines
      • ChimeriVax vaccines
      • Recombinant dengue vaccines based on non-flavivirus vectors
    • Dengue Vaccines
      • Conventional vaccines: empirically attenuated
      • strains of all four dengue serotypes have been
      • created by repeated serial passage in non-
      • permissive cell lines
        • Mahidol vaccine (licensed to Aventis Pasteur): after reducing the concentrations of serotype 3 strain: about 71% seroconversion against all four types
        • Walter Reed Army Institute for Research (licensed to Glaxo-SmithKline): 80-90% seroconversion against all four serotypes
      • THE KEY TO THE SUCCESS IN THE MANAGEMENT OF DENGUE IS…
      • GOOD CLINICAL EVALUATION
      • PROMPT & PRECISE
      • INTERVENTION