Severe Dengue: risk factors and management

1. Severe Dengue: risk factors and management 高雄長庚感染科 李允吉醫師

2. Outline • Dengue case management • Clinical manifestations and risk factors for severe dengue • Severe dengue in adults (KSCGMH preliminary data)

3. Dengue case management

5. Patient assessment • Warning signs • Abdominal pain or tenderness • Persistent vomiting • Clinical fluid accumulation • Mucosal bleed • Lethargy, restlessness • Liver enlargement >2 cm • Laboratory: increase in HCT concurrent with rapid decrease in platelet count Warning signs and/or co-existing conditions Pregnancy Infancy Diabetes mellitus Old age Renal failure No warning signs 1. Severe plasma leakage leading to shock or fluid accumulation with respiratory distress 2. Severe bleeding as evaluated by clinician 3. Severe organ involvement Emergency management Outpatient management Inpatient management

6. Initial patient assessment In which phase of disease is the patient? Day onset of illness How much oral fluid intake ? How much urine output ? Fluid losses: diarrhea, vomiting Presence of warning signs Risk factors: infancy, pregnancy, diabetes mellitus, old age, renal failure What was the patient’s pulse volume?

7. Patient assessment • Hemodynamic assessment is the foundation of dengue clinical management CCTV-R Skin color Capillary refill Temperature Pulse volume Pulse rate

8. Principle of case management DON’Tuse corticosteroids. They are not indicated and can increase the risk of GI bleeding, hyperglycemia, and immunosuppression. DON’Tgive ibuprofen, aspirin, or aspirin-containing drugs, and intramuscular injection. DON’T give platelet transfusions for a low platelet count. Platelet transfusions do not decrease the risk of severe bleeding and may instead lead to fluid overload and prolonged hospitalization. DON’T give half normal (0.45%) saline. Half normal saline should not be given, even as a maintenance fluid, because it leaks into third spaces and may lead to worsening of ascites and pleural effusions. DON’T assume that IV fluids are necessary. First check if the patient can take fluids orally. Use only the minimum amount of IV fluid to keep the patient well-perfused. Decrease IV fluid rate as hemodynamic status improves or urine output increases.

9. Dengue fever without warning signs (Outpatient Management) • Prevent dehydration (病人及家屬衛教): (1) Give plenty of fluids (not only water) (2) Watch for signs of dehydration ▶ Decrease in urination ▶ Few or no tears when child cries ▶ Dry mouth, tongue or lips ▶ Sunken eyes ▶ Listlessness, agitation, or confusion ▶ Fast heartbeat (>100/min) ▶ Cold or clammy fingers and toes ▶ Sunken fontanel in an infant • Watch for warning signs

10. Dengue fever with warning signs (Adequate/inadequate oral fluid) Monitor fluid intake/output and encourage oral fluid intake Obtain baseline complete blood count Monitor vital signs every 4 hours Does patient have adequate oral fluid intake? Adequate oral fluid intake Inadequate oral fluid intake Observe for warning signs and early shock Inpatient Management

11. Dengue fever with warning signs (Inpatient Management) Inadequate oral fluid intake ⃰ Normal saline, Ringer’s lactate Check HCT Give isotonic crystalloids⃰ in stepwise manner: 5-7ml/kg/h for 1-2 h 3-5ml/kg/h for 2-4 h Stable and no change or minimal change in HCT Patient improving: Reduce fluid (stepwise); reassess before each change 5-10 ml/kg/h for 1-2 h 3-5 ml/kg/h for 2-4 h 2-3 ml/kg/h for 2-4 h Stop IV fluids at 48 h Worsening vital signs and increasing HCT Continue isotonic crystalloids: 2-3ml/kg/h for 2-4 h Isotonic crystalloids: 5-10ml/kg/h for 1-2 h Adequate fluid and urine output (0.5 ml/kg/h); HCT decreases to baseline. Stop IVF therapy within 24–48 h Recheck HCT Reassess vital signs Not improved: Emergency management

12. How long does plasma leakage last? 24 – 48 hours

13. Compensated shock ⃰ Obtain HCT and organ function tests §Normal saline, Ringer’s lactate Systolic pressure maintained but has signs of reduced perfusion⃰ Isotonic crystalloid§5–10 ml/kg/h over 1 h Hemodynamic status not improved (HCT) Hemodynamic status improved Reduce fluid (stepwise): 1. 5–7 ml/kg/h for 1–2 h 2. 3–5 ml/kg/h for 2–4 h 3. 2–3 ml/kg/h for 2–4 h Decreasing HCT Increasing HCT Given isotonic crystalloid 10-20ml/kg bolus 1h Initiate transfusion RecheckHCT; reassess clinical status If: adequate fluid intake and urine output; HCT at baseline or slightly below baseline, Then: DC intravenous fluids (stop at 48 hours) Improving: Reduce fluid to 7-10ml/kg/h for 1-2 h Then reduce further

14. Hypotensive shock Obtain HCT and organ function tests ⃰ Normal saline, Ringer’s lactate §Gelatin-based, dextran-based and starch-based solutions Give 20 ml/kg isotonic crystalloid ⃰ or colloid§over 15 minutes Hemodynamic status not improved Hemodynamic status improved Isotonic crystalloid or colloid infusion at 10 ml/kg/h over 1 h Decreasing HCT Increasing HCT Reassess clinical status and HCT; if improving, reduce fluid in stepwise manner (IV crystalloid) 1. 5–7 ml/kg/h for 1– 2 h 2. 3–5 ml/kg/h for 2–4 h 3. 2–3 ml/kg/h for 2–4 h If patient continues to improve, stop at 48 h Give colloid 10–20 ml/kg over ½ to 1 hour Initiate transfusion Not improving; Repeat 2nd HCT Improving: Crystalloid/colloid 10 ml/kg/h for 1 hour, then reduce fluid

15. Phase of disease, day 3 vs. day 7 Hemodynamic state should be the principal driver of IV fluid therapy HCT level should only be guide

16. Rising or high HCT + Unstable hemodynamic state Active plasma leakage, fluid replacement Rising or high HCT + Stable hemodynamic state Does not require extra intravenous fluid, continue to monitor (encourage oral hydration) Decrease HCT + Unstable hemodynamic state Bleeding, need for urgent transfusion Decrease HCT + Stable hemodynamic state (+ phase of disease) Hemodilution or reabsorption, reduced or DC intravenous fluid

17. When to start and stop intravenous fluid therapy Febrile phase: oral fluid advice Critical phase: IV fluids are usually required for 24–48 hours Recovery phase: IV fluids should be stopped so that extravasated fluids can be reabsorbed

18. 4 Intravenous Fluid Regimens for DSSin the First Hour Clin Infect Dis 2001; 32:204–13

19. Three Fluid Solutions for Resuscitationin DSS • Kaplan–Meier Curves for Time from Study Entry to Initial (Panel A) and Sustained (Panel B) Cardiovascular Stability among Children in Group 1, According to the Resuscitation Fluid Received. N Engl J Med 2005; 353;9

20. Prophylaxis platelet transfusion in dengue Fever • Dengue patients with platelet count < 20 X 103 /uL Clin Infect Dis 2009; 48:1262–5

21. Preventive transfusion in dengue shock syndrome • Significant differences in the development of pulmonary edema and length of hospitalization (P<.05) (in preventive transfusions group) were observed • Preventive transfusions did not produce sustained improvements in the coagulation status in DSS J Pediatr. 2003 Nov; 143(5):682-4.

22. Platelet Transfusion in Dengue Fever • Acute lung injury after platelet transfusion in a patient with dengue fever Asian J Transfus Sci. 2014 Jul-Dec; 8(2): 131–134

23. Platelet Transfusion in Dengue Fever • Prophylactic platelet transfusions are not required in stable patients with platelet count below 20,000/μl. J Indian Med Assoc. 2011 Jan; 109(1):30-5.

24. Oral CorticosteroidTherapy in Dengue Infection • Randomized, Double-Blind Placebo Controlled Trial Clin Infect Dis 2012;55(9):1216–24

25. Balapiravir therapy in Dengue Infection • Randomized, Double-Blind Placebo Controlled Trial J Infect Dis 2013;207:1442–50

26. Chloroquine therapy in Dengue Infection • Double-blind, randomized, placebo-controlled trial PLoSNegl Trop Dis 2010; 4(8): e785

27. Clinical manifestations and risk factors for severe dengue

28. 台灣登革熱疫情(1998-20150906) Source: Taiwan CDC

29. Rash

30. Cutaneous hemorrhage

31. Retinal hemorrhage

32. Gastrointestinal bleeding

33. Pleural effusion

34. Pulmonary congestion and acute respiratory distress syndrome

35. Gallbladder swelling

36. Ascites

37. Acute abdomen in dengue N=1 N= 3 The importance of differential diagnosis in patients with acute abdomen in a dengue-endemic setting. Am J Trop Med Hyg 2006; 74: 901

38. Hyperlipasemia and acute pancreatitis in DHF • Hyperlipasemia developed in 14 patients with DHF • Pancreatitis was diagnosed in 3 patients Pancreas 2007; 35: 381

39. Spontaneous spleen rupture in DHF • 29-year-old female patient • Conservative management Am J Trop Med Hyg 2008; 78: 7

40. Myocarditis in dengue IntJ Infect Dis. 2010 Oct;14(10):e919-22

41. Rhabdomyolysis in dengue Am J Trop Med Hyg. 2015 Jan;92(1):75-81

42. HemophagocyticLymphohistiocytosis MMWR / January 24, 2014 / Vol. 63 / No. 3

43. Acute transverse myelitis in dengue J ClinVirol 2006; 35; 312

44. Concurrent bacteremia in dengue N=3 Clinicians should be alert to the potential for concurrent bacteremia when treating patients with DHF/DSS Am J Trop Med Hyg 2005; 72: 221

45. Case presentation • 71-year-old woman • Underlying: Senile dementia, hypertension, chronic anemia • Fever and malaise for 5 days • She was evaluated by her family physician and was prescribed some medication for a diagnosis of common cold • Gum bleeding and gross hematuriawere found one day before presentation at our emergency room

46. Case presentation • On examination, the patient appeared clear consciousness. She was afebrile with a temperature of 37°C, pulse rate 95 beats/min, and blood pressure 126/66 mm Hg (day 7 onset of illness) • Laboratory data showed leukopenia and thrombocytopenia • She living in dengue endemic area; and dengue virus infection was confirmed by serology test

47. Case presentation Haemodilution or reabsorption (29%) Platelet transfusion 12 units Platelet transfusion 12 units Admitted to ward at night time Dengue fever with warning signs No more gum bleeding and hematuria Intravenous fluid: N/S run 60cc/h

48. Case presentation - The patient became drowsy on the next day after admission (day 10 after illness onset). On examination she was unconsciousness with cold and clammy peripheries. Her blood pressure was 60/40 mmHg and with a heart rate of 95/minute. Immediately rapid saline intravenously infusion 1000cc (within 30 minute). Her blood pressure was 110/80 after fluid replacement. Additional fluid was given 500cc within 1 hour. - Maintenance intravenous fluid of 60cc/h and monitor hematocrit, platelet count and I/O. - Improvement of patient’s consciousness. Reduced intravenous fluid on day 2 after shock.

49. Case presentation • Pleural effusion, ascites and gallbladder swelling

50. Case presentation Day discharge from hospital • Day from onset illness to shock: 10th day • Plasma leak: pleural effusion, ascites, hemoconcentration • Critical phase: between 9th and 11th day after onset illness • Warning signs: mucosal bleeding (gum bleeding, hematuria), increase hematocrit concurrent decrease platelet count, drowsy (onset to shock: hours) (39%) Hemoconcentration