DECISION

ON PROMULGATION OF THE GUIDANCE ON DIAGNOSIS AND TREATMENT OF DENGUE HEMORRHAGIC FEVER

THE MINISTER OF HEALTH

Pursuant to the Government's Decree No. 188/2007/ND-CP dated December 27, 2007, defining the functions, tasks, powers and organizational structure of the Ministry of Health;

In consideration of the amendments to the “Guidance on diagnosis and treatment of Dengue fever and Dengue hemorrhagic fever” dated December 31, 2010;

At the request of the Director of Medical Service Authority - the Ministry of Health,

DECIDES:

Article 1. To promulgate together with this Decision the Guidance on diagnosis and treatment of Dengue hemorrhagic fever.

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Article 3. This Decision takes effect from the day on which it is signed. This Decision supersedes the Decision No. 794/QD-BYT dated March 09, 2009 on the promulgation of the “Guidance on diagnosis and treatment of Dengue fever and Dengue hemorrhagic fever”.

Article 4. Chief of the Ministry Office, the Chief Inspector of the Ministry, Directors of Departments affiliated to the Ministry of Health; Directors of hospitals affiliated to the Ministry of Health, Directors of Services of Health, heads of relevant units are responsible for the implementation of this Decision.

PP THE MINISTER
DEPUTY MINISTER




Nguyen Thi Xuyen

GUIDANCE

DIAGNOSIS AND TREATMENT OF DENGUE HEMORRHAGIC FEVER
(Promulgated together with the Decision No. 458/QD-BYT dated February 16, 2011 of the Minister of Health)

I. OVERVIEW

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This disease happens throughout the year and tends to increases during rainy seasons. This disease is caught by both children and adults. Symptoms of DHF are fever, hemorrhage, plasma leakage, possibly reduction of blood circulation volume, coagulation, organ failure that may lead to death if not diagnosed and cured early.

II. CLINICAL DEVELOPMENT OF DHF

Clinical symptoms of DHF are diverse and develop quickly. The disease strikes suddenly and goes through 03 phases: febrile phase, critical phase, and recovery phase. Early detection of this disease and understanding of clinical problems in each phase facilitate early diagnosis, correct and timely treatment to cure patients.

1. Febrile phase

1.1. Clinical manifestation

- Sudden and continuous high fever.

- Headache, anorexia, nausea.

- Petechiae.

- Muscle pain, joint pain, pain behind the eyes.

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- Usually skin hemorrhages, gingival bleeding or epistaxis.

1.2. Subclinical manifestation.

- Normal hematocrit.

- Platelet count is normal or reducing (above 100,000/mm³).

- Leukocyte count usually drops.

2. Critical phase: Usually 3^rd to 7^th day of the disease course

2.1. Clinical manifestation

a) The fever may or may not decrease.

b) The following manifestations are possible:

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+ Pleural effusion, peritoneal effusion, interstitial effusion, swollen eyelids, hepatomegaly, possibly pain.

+ Significant leakage of plasma will lead to shock manifested in restlessness, agitation, lethargy, cold extremities, cold and clammy skin, rapid and weak pulse, low pulse pressure (the difference between maximum and minimum blood pressure ≤ 20 mmHg), hypotension or undetectable blood pressure, decreased urine output.

- Hemorrhage:

+ Bleeding under the skin: scattered petechiae or ordinary petechiae in the front of both legs, the inside of both arms, abdomen, thighs, ribs, or bruises.

+ Mucous membrane hemorrhage: bleeding from the nose or gums, hematuria. Prolonged or early menstruation.

+ Bleeding from organs such as gastrointestinal tract, lungs, or brain is a severe manifestation.

c) Organ failures such as severe hepatitis, encephalitis, or myocarditis may be observed in severe cases. Those severe manifestations may be observed from patients without clear signs of plasma leakage or without shock.

2.2. Subclinical manifestation

- Hematocrit rises in comparison to the initial value or average value of the people in the same age group.

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- Enzyme AST, ALT usually rises.

- Coagulation may occur in severe cases.

- Pleural effusion and peritoneal effusion may be detected by ultrasound or x-ray.

3. Recovery phase

3.1. Clinical manifestation

Reabsorption of fluid into the vein from interstitial tissues occurs 24 - 48 hours after the critical phase. This phase lasts for 48 - 72 hours.

- The patient has no fever, regains appetite, urinate adequately, the condition improves.

- Pulse rate may be slow and ECG may be changed.

- Excessive fluid infusion during this phase may cause pneumochysis or heart failure.

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- Hematocrit returns to normal or lower due to blood dilution when fluid is reabsorbed.

- Leukocyte count usually rises after the fever reduces.

- Platelet count gradually returns to normal later than leukocyte count.

III. DIAGNOSIS

1. DHF is classified into 3 levels (by WHO in 2009):

- DHF.

- DHF with warning signs.

- Severe DHF.

Appendix 2: Levels of Dengue hemorrhagic fever.

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a) Clinical manifestation

Sudden and continuous high fever for 2 - 7 days with at least 2 of the following signs:

- Positive tourniquet test, skin hemorrhages, gingival bleeding or epistaxis.

- Headache, anorexia, nausea.

- Petechiae, rash.

- Muscle pain, joint pain, pain behind the eyes.

b) Subclinical manifestation

- Hematocrit is normal (no sign of blood coagulation) or rises.

- Platelet count is normal or slightly drops.

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1.2. DHF with warning signs.

Clinical symptoms of DHF and the following signs:

- Restlessness, lethargy.

- Pain in the liver area whether pressed or not.

- Enlarged liver > 2 cm.

- Frequently vomiting.

- Mucous membrane hemorrhage.

- Decreased urine output.

- Blood test:

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+ Platelet count drops quickly

The patients having the aforementioned signed must have their pulse, blood pressure, and urine amount monitored, undergo hematocrit test, platelet test, and be given fluid infusion.

1.3. Severe DHF

Manifestations:

- Severe plasma leakage that leads to hypovolaemic shock (Dengue shock syndrome), excess fluid accumulation in the pleural cavity or abdominal cavity

- Severe hemorrhage.

- Organ failure.

a) Dengue shock syndrome (DSS)

- Acute circulatory failure usually occurs on 3^rd - 7^th of the disease course, manifested in restlessness, agitation, or lethargy; cold extremities, cold and clammy skin; rapid and weak pulse, low pulse pressure (≤ 20 mmHg), hypotension or undetectable blood pressure; decreased urine output.

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+ DSS: signs of circulatory failure, rapid and weak pulse, low blood pressure or pulse pressure associated with cold and clammy skin, restlessness, or lethargy.

+ Profound DSS: profound shock, weak pulse, undetectable blood pressure.

- Notes: the disease may progress from mild phase to severe phase, thus clinical classification is necessary for forecasting and planning.

b) Severe hemorrhage

- Severe epistaxis, metrorrhagia, bleeding from the muscle and soft tissues, bleeding from the gastrointestinal tract and organs, usually associated with profound shock, thrombocytopenia, tissue anoxia, and metabolic acidosis that may lead to multiple organ failure and severe intravascular coagulation.

- Severe hemorrhage may also happen to patients that use anti-inflammatory medicines such as acetylsalicylic acid (aspirin), ibuprofen or corticoid, suffered from chronic hepatitis, gastric ulcer or duodenal ulcer.

c) Severe organ failure

- Acute liver failure, liver enzyme AST, ALT ≥ 1000 U/L.

- Acute kidney failure.

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- Myocarditis, heart failure, or failure of other organs.

2. Diagnosis of origins of dengue virus

2.1. Serological test

- Quick test:

+ Find NS1 antigen within the first 5 days of the disease.

+ Find IgM antibody from the 5^th day.

- ELISA test:

+ Find IgM antibody from the 5th day.

+ Find IgG antibody: take the second blood sample one week after the first one to find antibody dynamics (4 times greater).

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3. Differential diagnosis of:

- Viral typhus

- Febris Orientalis.

- Malaria.

- Septicemia caused by streptococcus suis, Meningococcemia, etc.

- Septic shock.

- Blood diseases.

- Acute diseases of the abdominal cavity, etc.

IV. TREATMENT

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Most cases are treated outside the hospital and monitored at local medical facilities, primarily treatment of symptoms and early detection of shocks to promptly respond.

1.1. Symptom treatment

- Administer antipyretics, loosen clothes and the body with warm water if the body temperature is 39⁰C or greater.

- The only permissible antipyretic is paracetamol, 10 - 15 mg/kg body weight/dose. Repeat the dose after 4 - 6 hours.

- Notes:

+ Total dose of paracetamol must not exceed 60 mg/kg body weight/24 hours

+ Do not use aspirin (acetyl salicylic acid), analgin, ibuprofen because they may cause hemorrhage or acidosis.

1.2. Early oral rehydration: encourage the patient to drink a lot of oresol or cooled boil water, juices (coconut, orange, lemon juices, etc) or porridge with salt.

2. Treatment of DHF with warning signs.

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- Perfusion:

+ Consider giving fluid infusion if the patient is not able to drink, is vomiting, showing signs of dehydration, lethargy, hematocrit rise though blood pressure is still stable.

+ Intravenous fluids: Ringer lactate, NaCl 0.9%.

Appendix 4: Fluid infusion flow chart for treatment of DHF with warning signs.

- Notes:

+ If the patient is ≥ 15 years of age, stops vomiting and is able to eat, perfusion may be stopped.

+ The patients in a special condition such as pregnant women, breastfed children, obese patients; suffering from other diseases such as diabetes, pneumonia, bronchial asthma, heart diseases, liver diseases, kidney disease, etc.; the patients living alone or away from medical facilities should be hospitalized.

3. Treatment of severe DHF

The patient must be hospitalized.

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a) DSS

- The following intravenous fluids must be prepared:

+ Ringer lactate.

+ Isotonic saline solution (NaCl 0.9%)

+ Macromolecular solution (dextran 40 or 70, hydroxyethyl starch (HES)).

- Infusion method

+ The lost plasma must be quickly replaced with Ringer lactate or NaCl 0.9% by intravenous infusion with 15 - 20 ml/kg body weight/hour.

+ Assess the condition of the patient after 1 hour; check hematocrit after 02 hours of infusion:

(α) After 01 hour, if the patient is no longer in the state of shock, pulse pressure is no longer low, pulse is strong again, limbs are warm, urine output increases, the infusion speed may be decreased to 10 ml/kg body weight/hour for 1 - 2 hours, then 7.5 ml/kg body weight/hour for 1 - 2 hours, then 5 ml/kg body weight/hour for 4 - 5 hours, and 3 ml/kg body weight/hour for 4 - 6 hours depending on clinical response and hematocrit.

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• If the shock subsides and hematocrit drops, the infusion speed shall be reduced to 10 ml/kg body weight/hour for 1 - 2 hours.  • If the shock keeps subsiding and hematocrit keeps dropping, the infusion speed shall be reduced to 7.5 ml/kg body weight/hour, then 5 ml/kg body weight/hour for 2 - 3 hours.

Keep monitoring the patient and infuse electrolyte solution intravenously if the condition is stable (more details in Appendix 2).

• If shock does not subside, central venous pressure (CVP) shall be measured to reach a solution.

If shock does not subside and hematocrit drops quickly (still above 35% though), examination shall be carried out to find organ hemorrhage and consider blood transfusion. Blood shall be transfused at 10 ml/kg body weight/hour.

Notes: Every change to the transfusion speed depends on the pulse, blood pressure, output of urine, heart and lung condition, hematocrit every one or two hours, and CVP.

Appendix 5: Fluid infusion as treatment of DSS in children.

b) Profound DSS

Appropriate treatment must be promptly administered if the patient passes into the state of profound shock (pulse or blood pressure is undetectable (HA = 0))

- Lower the head of the patient.

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- Fluid infusion:

+ If the patient is under 15 years of age: inject ringer lactate or isotonic saline solution into the vein at 20 ml/kg body weight for 15 minutes. Then the patient shall be reassessed:

• If blood pressure and pulse are back to normal, infuse macromolecular solution at 10 ml/kg body weight/hour and handle similarly to DHF.

• If pulse is rapid, blood pressure or pulse pressure is low: infuse macromolecular solution at 15 - 20 ml/kg body weight/hour, and follow the instructions in (β).

• If blood pressure and pulse are still undetectable: inject macromolecular solution directly into the vein at 20 ml/kg body weight for 15 minutes. CVP should be measured to reach a solution. • If pulse and blood pressure are perceptible, macromolecular solution shall be infused at 15 - 20 ml/kg body weight/hour, and follow the instructions in (β).

Appendix 6: Fluid infusion as treatment of profound DSS in children.

+ If the patient is ≥ 15 years of age: follow the diagram in Appendix 7.

* Recommendations during fluid infusion

- Stop the infusion when blood pressure and pulse are back to normal and urine output increases. Rehydration is not necessary from 24 hours after the shock diminishes.

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- If the patient is admitted in the state of shock and has been given treatment for shock before being transferred, he will be treated as in a case of no improvement (recurrent shock). Pay attention to the amount of fluid infused before hospitalization to calculate the amount of fluid to be infused.

- If the adult patient suffers from a recurrent shock, no more than 1,000 ml of Dextran 40 or no more than 500 ml of Dextran 70 shall be used. If the condition does not improve, the following are recommended:

+ Measure CVP to give rehydration

+ Closely monitor the pulse, blood pressure, breath rate, and find internal hemorrhage to give transfuse blood in time.

+ Great care must be taken when performing the procedure at the positions where bleeding is hard to stop such as jugular vein and subclavian vein.

- In event of low pulse pressure, especially after a period of recovery, the following causes must be identified:

+ Hypoglycemia

+ Recurrent shock due to insufficient compensation for leakage.

+ Internal hemorrhage

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- Pay attention to regulating electrolyte disorder and acid-base balance: Hyponatremia usually occurs in most cases of persistent profound shock, and sometimes with metabolic acidosis. For this reason, it is necessary to find measure the degree of electrolyte disorder and, if possible, measure gases in blood of patients suffering from profound shock or patients that do not respond quickly to treatment.

3.2. Treatment of severe hemorrhage.

a) Transfusion of blood and blood products

- When blood group of the patient in shock must be determined for future blood transfusion where necessary.

- Transfuse erythrocyte or whole blood:

+ Shock does not subside after rehydration; hematocrit significantly drops (still above 35%).

+ Severe hemorrhage.

b) Transfusing platelets

- When platelet counts falls below 50,000/mm³ with severe hemorrhage.

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c) Consider infusing fresh, cold, precipitated plasma when the patient suffers from coagulation that leads to severe hemorrhage.

3.3. Treatment of severe organ failure

a) Liver injury, acute liver failure

- Respiratory assistance: give oxygen therapy or NCPAP; consider placing endotracheal tube for mechanical ventilation if the patient suffers from persistent shock.

- Circulatory assistance

+ If shock occurs: treat with NaCl 9% or a macromolecular solution. Do not use Ringer lactate.

+ If shock does not occur: infuse electrolyte as demanded or 2/3 of the demand when the patient suffers from perception disorder.

- Control hypoglycemia: keep blood sugar at 80-120mg%, inject glucose 30% intravenously at 1-2 ml/kg and keep glucose at 10-12.5% when injecting through peripheral veins or glucose 15-30% through central vein (note that the solution is mixed with electrolyte).

- Adjusting electrolyte:

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Blood sodium < 120 mmol/L associated with perception disorder: infuse NaCl 3% intravenously for one hour, 6-10 ml/kg.

Blood sodium < 120-125 mmol/L without perception disorder: infuse NaCl 3% intravenously for 2 - 3 hour, 6-10 ml/kg.

+ Hypokelemia: give oral or intravenous fluid therapy.

- Regulating metabolic acidosis: infuse bicarbonate 1-2mEq/kg (slow intravenous injection)

- Regulating coagulation/gastrointestinal hemorrhage:

+ Frozen fresh plasma 10-5 ml/kg: coagulation + gastrointestinal hemorrhage.

+ Frozen precipitate 1 unit per 6 kg: gastrointestinal hemorrhage + fibrinogen < 1g/L.

+ Condensed platelet: gastrointestinal hemorrhage + platelet count < 50000/mm³.

+ Vitamin K1: 1mg/kg/day (not more than 10 mg of slow intravenous injection for 3 days.

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- Perception disorder/convulsion:

+ Prevention of cerebral edema: mannitol 20% 2.5ml/kg/30 minutes x 3-4 times per day.

+ Prevention of recurrent convulsions: slow intravenous injection of diazepam 0.2-0.3 mg/kg or slow intravenous injection of midazolam 0.1 - 0.2mg/kg. Contraindication: phenobarbital.

+ Low blood ammonia: douching with warm saline water, lactulose, metronidazol, neomycin (gavage).

- Broad-spectrum systemic antibiotic. Avoid using the antibiotics that are absorbed through the liver such as pefloxacine and ceftraxone.

- Do not use high doses of paracetamol due to its toxicity to the liver.

- Notes: Pay attention to intensive shock treatment if shock occurs during treatment of liver injury. Provide early respiratory assistance if shock does not subside. Monitor the levels of electrolytes, blood sugar, blood gases, blood ammonia, blood lactate, and coagulation every 4 - 6 hours to make timely intervention.

b) Acute renal failure: Conversation and hemodialysis when indicated and hemodynamics is stable. Continuous renal replacement therapy (CRRT) shall be administered if manifestations of multi-organ failure or acute renal failure associated with unstable hemodynamics are observed. Hemodialysis shall be administered when hemorrhagic fever is associated with acute renal failure.

- Electrolyte acid-base disorder without responding to medical treatment.

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+ Developing blood sodium disorder ([Na] > 160 or < 115 mmol/L).

+ Severe blood acidification without responding to bicarbonate infusion (pH < 7.1).

- High blood urea: perception disorder, vomiting, gastrointestinal hemorrhage, blood urea > > 200 mg% and/or creatinine >1.5 mg% (small children) or > 2 mg% (older children).

3.4. Fluid without response to medical treatment

- Congestive heart failure, hypertension.

- Acute pneumochysis.

- Continuous renal replacement therapy shall be administered when multi organ failure associated with acute renal failure or acute renal failure associated with unstable hemodynamics is observed.

3.5. Cerebral Dengue encephalitis, perception disorder, convulsion

- Respiratory assistance: oxygen therapy, low pressure CPAP (4-6cmH₂O), or mechanical ventilation if the other methods fail.

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- Treat convulsion

- Treat cerebral edema.

- Reduce fever.

- Provide liver assistance if injury is found.

- Regulate electrolyte disorder or acid-base imbalance.

- Ensure adequate nutrition and care.

- Early rehabilitation.

3.6. Myocarditis, heart failure: dopamine, dobutamine, measure CVP to assess circulatory volume.

4. Oxygen therapy: every patient that suffers from a shock must be given low-flow oxygen delivery.

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- If the fever persists, CVP must be measures to reach a solution.

- If adequate fluid has been infused but blood pressure does not increase and central venous pressure has exceeded 10 cm of water, intravenous infusion shall be administered.

+ Dopamin, 5-10 mcg/kg body weight/minute.

+ If dopamin has been used at 10 mcg/kg body weight/minute but blood pressure does not increase, dobutamin shall be used at 5 - 10 mcg/kg body weight/minute.

6. Other treatment methods

- When peritoneal effusion or pleural effusion occurs and causes dyspnea, SpO₂ shall be reduced to below 92%. It is recommended that the patient be given NCPAP prior to this reduction. Consider aspirating to reduce fluid in peritoneum or pleura if the condition does not improve.

- Patients with DHF shall be nursed in accordance with Appendix 12.

7. Nursing and monitoring patients in shock

- Keep the patient warm.

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- Measure hematocrit once every 1 - 2 hours during the first 6 hours of the shock, and once every 4 hours thereafter until shock is treated.

- Record the output and input of water over 24 hours.

- Measure the output of urine.

- Monitor the effusion of fluid into the peritoneum, pleura, or pericardium

8. Criteria for discharging inpatients

- Absence of fever for 2 days, consciousness.

- Normal pulse and blood pressure.

- Platelet count is over 50,000/mm3.

9. Prevention

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- No vaccines are available.

- Primary prophylactic measures are controlling vectors such as avoiding mosquito bites, exterminating mosquito larva and mosquitoes, and removing stagnant water.

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