1. ANITA G. MARASIGAN, MD FPPS, FSPCCM
FLUID MANAGEMENT OF DENGUE FEVER AND DENGUE HEMORRHAGIC FEVER (2010 INTERIM GUIDELINES)
ANITA G. MARASIGAN, MD FPPS, FSPCCM
ASSOCIATE PROFESSOR
FEU – NRMF MEDICAL CENTER

2. OBJECTIVES:
To update the section on fluid management of the 2008 PPS Dengue Evidence – based guidelines.
To develop clinical algorithms on fluid resuscitation of patients with Dengue based on clinical features.

3. Proposed WHO Classification and Levels of Severity 2009
Current WHO Case Definition of Dengue and Levels of Severity (1997) as adapted by the PPS Clinical Practice Guidelines of Dengue 2008
Proposed WHO Classification and Levels of Severity 2009
Case Definition for Dengue Fever
Probable:
An acute febrile illness with 2 or more of the following:
headache
Retro-orbital pain
Arthralgia
Rash
Hemorrhagic manifestations
Leukopenia
Supportive serology
Confirmed:
a case confirmed by laboratory criteria
Non severe Dengue w/o Warning Signs:
Probable Dengue:
live in/travel to dengue endemic areas.
Fever and 2 of the following criteria
Nausea
Vomiting
Aches and Pains
Tourniquet test positive
Laboratory Confirmed Dengue:
(impt. when no sign of plasma leakage)

4. Current WHO Case Definition of Dengue and Levels of Severity (1997) as adapted by the PPS Clinical Practice Guidelines of Dengue 2008
Case Definition for: Dengue Hemorrhagic Fever (DHF)
The Following must ALL be present:
1. Fever, or history of fever, lasting for 2 to 7 days, occasionally biphasic
2. Hemorrhagic tendencies evidenced by at least one of the following:
(+) tourniquet test
Petechiae, ecchymosis, purpura
Bleeding from the mucosa, GIT, injection sites or other locations
Hematemesis or melena

5. Current WHO Case Definition of Dengue and Levels of Severity (1997) as adapted by the PPS Clinical Practice Guidelines of Dengue 2008
Case Definition for: Dengue Hemorrhagic Fever (DHF)
3. Thrombocytopenia (100,000 cells/mm3 or less)
4. Evidence of plasma leakage due to increased vascular permeability, manifested by at least one of the following:
A rise in the hematocrit equal to or greater than 20% above average for age, sex and population
a drop in the hematocrit following volume replacement treatment equal to or greater than 20% of baseline
Signs of plasma leakage such as pleural effusion, ascites and hypoproteinemia.

6. Hypotension for age AND Cold, clammy skin and restlessness
Current WHO Case Definition of Dengue and Levels of Severity (1997) as adapted by the PPS Clinical Practice Guidelines of Dengue 2008
Case Definition for: Dengue Shock Syndrome (DSS)
All of the four criteria for DHF must be present, plus evidence of circulatory failure manifested by:
Hypotension for age AND
Cold, clammy skin and restlessness

7. DHF Grade I Grading of Severity of DHF/DSS
Current WHO Case Definition of Dengue and Levels of Severity (1997) as adapted by the PPS Clinical Practice Guidelines of Dengue 2008
Proposed WHO Classification and Levels of Severity 2009
Grading of Severity of DHF/DSS
DHF Grade I
Fever accompanied by non-specific constitutional signs & symptoms such as anorexia, vomiting, & abdominal pain
The only hemorrhagic manifestation is a (+) tourniquet test &/or easy bruising
Non severe Dengue w/o warning signs OR
Dengue w/ (Mild) warning signs
Fever and 2 of the following criteria:
Nausea, Vomiting
Rash
Aches & pains
Tourniquet test positive
Leukopenia
Any mild warning sign, eg. Mild abdominal pain or tenderness, mild liver enlargement

8. DHF Grade II Dengue w/ warning signs
Current WHO Case Definition of Dengue and Levels of Severity (1997) as adapted by the PPS Clinical Practice Guidelines of Dengue 2008
Proposed WHO Classification and Levels of Severity 2009
Grading of Severity of DHF/DSS
DHF Grade II
Spontaneous bleeding in addition to manifestations of Grade I patients usually in the form of skin or other hemorrhages (mucocutaneous), GIT
Dengue w/ warning signs
Abdominal pain or tenderness
Persistent vomiting
Clinical fluid accumulation
Mucosal bleed
Lethargy, restlessness
Liver enlargement >2cm
Laboratory: increase in Hct concurrent with rapid decrease in platelet count
Requires strict observation & medical intervention

9. Proposed WHO Classification and Levels of Severity 2009
Current WHO Case Definition of Dengue and Levels of Severity (1997) as adapted by the PPS Clinical Practice Guidelines of Dengue 2008
Proposed WHO Classification and Levels of Severity 2009
DHF Grade III
Circulatory failure manifested by rapid, weak pulse & narrowing of pulse pressure or hypotension w/ the presence of cold clammy skin and restlessness
Severe Dengue
Should be considered if the patient is from an area of dengue risk presenting with fever of 2-7 days plus any of the following features:
Severe plasma leakage, leading to:
Shock
Fluid accumulation w/ resp. distress
Severe bleeding, as evaluated by the clinician
Severe organ impairment
Liver: AST or ALT > 1000
CNS: impaired consciousness
Heart & other organs
DHF Grade IV
Profound shock w. undetectable blood pressure or pulse

10. Notes:
Shock
Is a critical condition that results from inadequate delivery of oxygen and nutrients to the tissues to meet metabolic demands.
Characterized by:
Inadequate perfusion
Low cardiac output

11. MOD ↓ Perfusion ↓ Cardiac Output Tissue hypoxia Anaerobic metabolism
↑ Lactic acid
& CO2
Irreversible cellular damage
Cardiovascular damage
MOD

12. SEVERITY OF SHOCK Compensated shock Hypotensive shock
signs of reduced perfusion as long as SBP is maintained
Hypotensive shock
When compensatory mechanism fails & SBP drops
SBP of <90mmHg or MAP <70mmHg or
SBP decrease of >40mmHg of <2 SD below normal for age

13. ASSESSMENT Level of consciousness Heart rate – Increased
CRT – sluggish, delayed, > 2 secs.
Pulse pressure – narrow
Peripheral pulses – thready, absent
Blood pressure – decreased
Output – decreased (<1mL/kg/hr in infants)
(<30ml/kg/hr in adolescents)
Skin – cold, diaphoretic

14. TABLE 4: HEMODYNAMIC ASSESSMENT: CONTINUM OF HEMODYNAMIC CHANGES
PARAMETERS
STABLE CONDITION
COMPENSATED SHOCK
HYPOTENSIVE SHOCK
Sensorium
Clear & Lucid
(shock can be missed if you don’t touch the patient)
Change of mental status (restless & combative)
CRT
Brisk
(<2sec )
Prolonged (>2sec)
Very prolonged, mottled skin
Extremities
Warm & pink
Cool peripheries
Cold & clammy
Peripheral Pulse
Good volume
Weak & thready
Feeble or absent
Source: WHO & Special Programme for Research & Training in Tropical Diseases, Dengue Guidelines for Diagnosis, Treatment, Prevention & Control, 2009

15. TABLE 4: HEMODYNAMIC ASSESSMENT: CONTINUM OF HEMODYNAMIC CHANGES
PARAMETERS
STABLE CONDITION
COMPENSATED SHOCK
HYPOTENSIVE SHOCK
Heart Rate
Normal for age
Tachycardia
Severe tachycardia w/ bradycardia in late shock
Blood Pressure
Normal pulse pressure for age
Normal SBP but rising DBP.
Narrowing pulse pressure,
Postural hypotension
Narrowed pulse pressure (<20mmHg) Hypotension, Unrecordable BP,
Metabolic Acidosis
Resp. Rate
Tachypnea
Hyperpnea, Kussmaul breathing
Source: WHO & Special Programme for Research & Training in Tropical Diseases, Dengue Guidelines for Diagnosis, Treatment, Prevention & Control, 2009

16. Fluid Management of Dengue Fever & Dengue Hemorrhagic Fever
A. Fluid Management for patients w/ DF/DHF (Dengue w/o warning signs) who are not admitted
In patients w/ DF/DHF Grade I who are not admitted, oral rehydration solution should be given as follows based on weight, using currently recommended ORS
Reduced osmolarity ORS containing Na 45 – 60mmol/L
Sports drinks (Na), <20meqs should not be given
Body Weight (Kg)
ORS to be given
> 3-10
100 mL/kg/day
> 10-20
75 mL/kg/day
> 20–30
50-60 mL/kg/day
> 30-60
40-50 mL/kg/day

17. Fluid Management of Dengue Fever & Dengue Hemorrhagic Fever
B. Fluid Management for patients who are admitted, without shock (DH/DHF Grade I & II or Dengue w/o warning signs
Isotonic solutions (D5LRS, D5 Acetate Ringers, D5 NSS or 0.9 NaCl) are appropriate for DHF patients who are admitted but without shock. Maintenance IVF computed using the caloric expenditure method (Holliday Segar Method) or calculation based on Weight (Barnes & Young Method)
Body Weight (Kg)
Total Fluid Requirement (mL/day)
0-10
100 mL/kg
> 10-20
1000 mL + 50mL/kg for each kg > 10kg
> 20
1000 mL + 50mL/kg for each kg > 20kg

18. Fluid Management of Dengue Fever & Dengue Hemorrhagic Fever
If the patient shows signs of mild dehydration, the volume needed for mild dehydration is added to maintenance fluids over the next 6-8 hours.
The following formula may be used to calculate the required volume of intravenous fluid to infuse:
Maintenace IVF + Fluids as for Mild Dehydration
Where volume of fluids for mild dehydration is computed as follows (to be added to the maintenance fluid volume):
Infant
50ml/kg/6-8 hours
Older Child or Adult
30 mL/kg/6-8 hours

19. Fluid Management of Dengue Fever & Dengue Hemorrhagic Fever
Periodic reassessment is needed so that fluid rate may be adjusted accordingly.
After 6-8 hours, fluid rate is computed at maintenance rate over hours
Clinical parameters should be monitored closely & correlated w/ hematocrit. This will ensure adequate hydration, avoiding under and over hydration. The IVF rate may be decreased any time as needed.

20. Improvement (b) See table 4
C. Fluid Management for patients ADMITTED to the hospital w/ DHF GRADE III (Compensated Shock)
Compensated shock (systolic pressure maintained but has signs of plasma leakage (hemoconcentration or reduced perfusion)
Box A. Obtain baseline Hct (a) Fluid resuscitation with plain isotonic crystalloid 10-15ml/kg/hour over 1 hour. Give oxygen support
Improvement (b) See table 4
Yes No
Box B. IV Crystalloid 5-7ml/kg/hr for 1-2 hours, then reduce to 3-5 ml/kg/hr for 2-4 hours;
reduce to 2-3 ml/kg/hr for 2-4 hours;
Fluids should not exceed 3L/day to avoid fluid overload.
If feasible, monitor Hct every 8-12 hours or as necessary (a)
Reassess hemodynamic status frequently (see table 4) including urine output (f)
Monitor signs of bleeding
If patient is stable & Hct increases by 10% from baseline, correlate clinically & assess need to increase fluid rate
If patient is unstable and Hct increases, go to Box B.
If patient is unstable & there is a sudden drop in Hct, look for signs of bleeding. Consider transfusion w/ fresh whole blood 20ml/kg or pRBC 10ml/kg
If patient is stable for 48 hours, stop IVF or give maintenance fluids or ORS

21. Improvement (b) See table 4
C. Fluid Management for patients ADMITTED to the hospital w/ DHF GRADE III (Compensated Shock)
Compensated shock (systolic pressure maintained but has signs of plasma leakage (hemoconcentration or reduced perfusion)
Box A. Obtain baseline Hct (a) Fluid resuscitation with plain isotonic crystalloid 10-15ml/kg/hour over 1 hour. Give oxygen support
Improvement (b) See table 4
Yes No
Box C. Administer 2nd bolus of fluid, colloid/crystalloid (c ) 10-20ml/kg/hr in 1 hour
Box B.
Box D. If there are signs of occult/ overt bleeding
Patient is stable
Hct Decreases
Patient is unstable
Hct Increases
Administer 3rd bolus of fluid (colloid/ crystalloid) 10-20ml/kg/hr for 1 hour
Go to Box B
Box E. If patient does not improve, consider inotropes (d) & refer to tertiary center
If patient improves, go to Box B

22. If patient does not improve, go to Box E
C. Fluid Management for patients ADMITTED to the hospital w/ DHF GRADE III (Compensated Shock)
Compensated shock (systolic pressure maintained but has signs of plasma leakage (hemoconcentration or reduced perfusion)
Box A. Obtain baseline Hct (a) Fluid resuscitation with plain isotonic crystalloid 10-15ml/kg/hour over 1 hour. Give oxygen support
Improvement (b) See table 4
Yes No
Box B.
Box C.
Box D. If there are signs of occult/ overt bleeding, initiate transfusion with fresh whole blood 20ml/kg or prbc 10ml/kg
Reassess hemodynamic status & bleeding parameters
If improved, go to Box B
If patient does not improve, go to Box E

23. Improvement (b) See table 4
D. Fluid Management for patients admitted to the hospital w/ shock DHF IV/DSS (Hypotensive Shock)
HYPOTENSIVE SHOCK
Box A. Obtain baseline Hct (a) fluid resuscitation w/ 20ml/kg plain isotonic crystalloid or colloid over 15 mins. ( c). Give oxygen support
Improvement (b) See table 4
Yes No
If patient is stable & Hct increases by 10% from baseline, correlate clinically & assess need to increase fluid rate
Box B. Crystalloid/ Colloid 10mL/kg/hr for 1 hr, then continue w/:
5-7ml/kg/hr for 1-2 hrs;
Reduce to 3-5 ml/kg/hr for 2-4 hrs;
Reduce to 2-3 ml/kg/hr for 2-4 hrs.
Fluids should not exceed 3L/day to avoid fluid overload.
If feasible, monitor Hct every 6 hrs or as necessary. Reassess hemodynamic status frequently (see table 4) including output (f). Monitor signs of bleeding.
If patient is unstable & Hct increases, go to Box B.
If patient is unstable & there is a sudden drop in Hct, look for signs of bleeding. Consider transfusion w/ fresh whole blood 20ml/kg or
pRBC 10ml/kg
If patient is stable for 48 hours, stop IVF or give maintenance fluids or ORS

24. Improvement (b) See table 4
D. Fluid Management for patients admitted to the hospital w/ shock DHF IV/DSS (Hypotensive Shock)
HYPOTENSIVE SHOCK
Box A. Obtain baseline Hct (a) fluid resuscitation w/ 20ml/kg plain isotonic crystalloid or colloid over 15 mins. ( c). Give oxygen support
Improvement (b) See table 4
Yes No
Box C. Administer 2nd bolus of fluid, (colloid) 10-20ml/kg over ½ to 1 hr. Check hemodynamic parameters (see table 4)
Box D. If there are signs of occult/ overt bleeding initiate transfusion w/ fresh whole blood 20ml/kg or prbc 10ml/kg
Reassess hemodynamic status & bleeding parameters
Box B.
Patient is stable
Hct Decreases
Patient is unstable
Hct Increases
Reduce IVF rate to 7-10ml/kg/hr for 1-2 hrs
Administer 3rd bolus of fluid (colloid/ crystalloid) 10-20ml/kg/hr for 1 hour
If improved, go to Box B
If patient improves, go to Box B
Box E. If patient does not improve, consider inotropes (d) & refer to tertiary center
If patient remains stable, go to Box B.
If patient doesn’t improve, go to Box E

25. Notes
If Hct is not readily available, assess hemodynamic status of patient using parameters in table 5.
Assessment of improvement should be based on 7 parameters: mental status, heart rate, blood pressure, respiratory rate, capillary refill time, peripheral blood volume and extremities

26. Crystalloids (Ringer’s Lactate or 0.9 NaCl Solutions
Have been shown to be safe & effective as colloid solutions (dextran, starch or gelatin
Comparable to colloids in terms of total amount of fluids used in resuscitation in moderately severe (compensated) dengue shock8-12
Colloids are associated with increased risk of allergic reactions and new bleeding manifestations10-11
Colloids may be used in patients who primarily present with hemodynamic instability
8-12 Jalal SLR et al, The use of colloids and crystalloids in pediatric dengue shock; Dung NM et al, Fluid replacement in DSS; Ngan Ngo Thi et al,. Acute management of dengue; Wills Ba et al, Comparison of 3 fluid solutions for resuscitation; Prasetyo RV et al Comparison of efficacy and safety between hydroxyethyl starch and ringer lactate in children
10-11 Ngan Ngo Thi et al,. Acute management of dengue; Wills Ba et al, Comparison of 3 fluid solutions for resuscitation

27. Crystalloids (0.9% saline/ Normal saline/ NSS)
Saline is a suitable option for initial fluid resuscitation, but repeated large volumes of 0.9% saline may lead to hyperchloremic acidosis
Hyperchloremic acidosis – may aggravate or be confused with lactic acidosis from prolonged shock
When serum Cl level exceeds normal range, it is advisable to change the to other alternatives such as Ringer’s lactate solution

28. Ringer’s Lactate
Has lower Na (131mmol/L) and Cl (115mmol/L) and osmolality of 273mOsm/L
It may not be suitable for resuscitation of patients with severe hyponatremia
It is a suitable solution after 0.9 Saline has been given and the serum Cl level has exceeded the normal range
Avoided in liver failure and patients taking metformin where lactate metabolism may ne impaired

29. Colloids
The types of Colloids are gelatin based, dextran based & starch based solutions
One of the biggest concerns regarding their use is their impact on coagulation
Dextrans – may bind to von Willebrand factor/Factor VIII complex and impair coagulation the most
Dextran 40 can potentially cause an osmotic renal injury in hypovolemic patients

30. Colloids
Gelatin
has the least effect on coagulation among all the colloids but has the highest risk of allergic reaction
Allergic reactions: Fever, chills and rigors have also been observed in Dextran 70

31. Hypotension Systolic pressure of <90mmHg
Mean arterial pressure of <70mmHg in adults
Systolic blood pressure decrease of >40mmHg of <2 standard deviation below normal for age
In children below 10 years of age the 5th centile for systolic pressure can be determined by the following formula:
Systolic blood pressure = 70 + (age in yrs x 2)mmHg

32. Urine Output
A good urine output indicates sufficient circulatory volume and may be used as an index or guide for decreasing the amount of fluid administered
An adequate urine output is at least 1ml/kg/hr & urine specific gravity of is ideal
WHO Dengue Guidelines 2009 – 0.5cc/kg/hr is considered acceptable and may have been chosen to avoid congestion in the course of the disease
Monitor urine output hourly till the patient is out of shock then 1-2 hourly

33. Inotropes
The use of inotropes should be decided on carefully and it should be started after adequate fluid volume has been administered.
To calculate the AMOUNT of DOPAMINE to be added to 100 mL of IV base solution:
mg of Dopamine = 6 x desired dose (mcg/kg/min) x wt(kg)
desired fluid rate (ml/hr)

34. Inotropes
To calculate the VOLUME of Drug to be added to 100 mL of IV base solution:
mL of Dopamine = mg of drug (determined using formula above)
Concentration of drug (mg/mL)
Preparation of Dopamine: 40mg/mL and
80mg/mL

35. Appendix A Calculation of Fluids in Obese or Overweight Patients
For Obese & Overweight Patients, Use the Ideal Body Weight for Calculation of Fluid Infusion
Estimated Body Weight or IBW (kg)
Normal Maintenance fluid (mL/hr) based on Holliday-Segar Formula
Fluid Regimen based on 2-3ml/kg/hr (ml/hr)
Regimen based on 1.5-2mL/hr (ml/hr) 5 10
10-15 20
20-30 15 30
30-45 60
40-60 25 65
50-75 70
60-90 35 75
70-105 40 80
80-120 50 90
100
90-120
110
105—140
120

36. Estimated Ideal Body Weight for Overweight
or Obese Adults
Height in cm
Estimated Ideal Body weight in kg for Adult Males
150 50
45.5
160 57 52
170 66
61.5
180 75 70

37. Causes of Fluid Overload
Excessive and/or too rapid intravenous fluids
Incorrect use of hypotonic rather than isotonic crystalloid solution
Inappropriate use of large volumes of intravenous fluids in patients with unrecognized severe bleeding
Inappropriate transfusion of fresh-frozen plasma, platelet concentrates and cryoprecipitates
Continuation of intravenous fluids after plasma leakage has resolved (24-48 hrs from defervescence)
Co-morbid conditions such as congenital or ischemic heart disease, chronic lung disease and renal disease

38. Early Clinical Features of Fluid Overload
Respiratory distress, difficulty in breathing
Rapid breathing
Chest wall indrawing
Wheezing rather than crepitant rales
Large pleural effusions
Tense ascites
Increased jugular pressure
hypertension

39. Sample Monitoring Sheet for Dengue Patients
Appendix C
Sample Monitoring Sheet for Dengue Patients
Parameters
Date
Time
Sensorium
Body temperature
Respiratory rate
Heart Rate
Bloo pressure
Pulse pressure/ volume
Capillary refill time
Temperature of extremities
Abdominal pain
Vomiting
Bleeding
IVF infusion rate
Urine Output

40. Members of the Technical Working Group on the 2010 PPS Interim Guidelines on Fluid Management of DF/DHF
Ma. Liza Antoinette M. Gonzales, MD: Overall Chair and Chair, Committee on Dengue, HV/AIDS, another Emerging Infectious disease
Maria Anna P. Banez, MD: Co-chair, Committee on Dengue, HIV/AIDS, and other Emerging Infectious Diseases
Members:
Cynthia A. Aguirre , MD Benjamin T. Lim, MD
Gyneth Lourdes G. Bibera , MD Anna Lisa T. Ong-Lim, MD
Rosario Z. Capeding , MD Ma. Louisa U. Peralta , MD
Reynaldo C. De Castro, Jr. , MD Anita G. Marasigan, MD
Flerida G. Hernandez , MD Ma. Norma V. Zamora , MD
Magdalena Lagamayo , MD
Adviser: Arturo C. Ludan, MD
Anna Lisa T. Ong-Lim , MD
Anita G. Marasigan , MD

41. p
THANK YOU !