Severe Dengue Infection in ICU. Shirish Prayag MD, FCCM Pune, India

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1 Severe Dengue Infection in ICU Shirish Prayag MD, FCCM Pune, India

2 Greetings from India

3 Declaration Honararia from MSD, Astra Zenecea, Fresenius Kabi, Pfizer, Intas, Glenmark for conducting lectures. No conflict in relation to this talk

4 Dengue Most important viral disease transmitted by a vector Half the world s population lives in areas which are at risk

5 Aedes Aegypti mosquito

6 NEGLECTED TROPICAL DISEASE

7 Prior to 1970, only 9 countries had DEN epidemic Now > 100 countries have

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9 The incidence of dengue has grown dramatically around the world in recent decades. Over 2.5 billion people over 40% of the world's population are now at risk from dengue. WHO currently estimates there may be million dengue infections worldwide every year

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11 Factors responsible for the global resurgence of DF Unprecedented population growth, Unplanned urbanisation, Uncontrolled urbanisation Increased air travel, Lack of effective mosquito control, Deterioration, during the past 30 years, of public health infrastructure.

12 An estimated people with severe dengue require hospitalization each year, a large proportion of whom are children. About 1 to 2.5% of those affected die. 12,500 die every year

13 Incidence in million cases 1.6 million from Americas 4,90,000 severe Dengue

14 35 people die every day

15 Although typically considered a childhood disease, recent studies have suggested an increased incidence of dengue infection, and particularly of severe infection, in adults J Clin Virol 2007;39: J Microbiol Immunol Infect 2006;39: Trop Med Int Health 2004;9: Emerg Infect Dis 2006;12:

16 Severe Dengue in SE Asia The incidence of the severe disease, DHF, has increased dramatically in Southeast Asia, the South Pacific, and the American tropics in the past 25 years, with major epidemics occurring in many countries every 3-5 years [CDC Health Information for International Travel 2008 ]

17 Problems with dengue data Dengue is difficult to diagnose. Some countries report severe dengue cases only; Others report all dengue cases. Some countries report only laboratory-confirmed cases whereas others report suspected cases as well. Problems of over- and under-diagnosis, incomplete reporting, and delays also weaken the data

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20 Problems with dengue data Dengue is difficult to diagnose. Some countries report severe dengue cases only; Others report all dengue cases. Some countries report only laboratory-confirmed cases whereas others report suspected cases as well. Problems of over- and under-diagnosis, incomplete reporting, and delays also weaken the data

21 Prognosis of Dengue Ill understood combination of viral, immunological and host factors.

22 Factors predisposing to severity Thisyacorn, Clin Inf Dis

23 DF, Dengue Hemorrhagic Fever (DHF), Dengue Shock Syndrome (DSS) Dengue without Warning Signs Dengue with Warning Signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) Severe Dengue (SD; dengue with severe plasma leakage, severe bleeding, or organ failure

24 What brings the Dengue patients to ICU? Severe Dengue [ DSS ] MODS Severe Hepatitis ARDS Encephalitis Myocarditis Thrombocytopenia leading to IC Bleed

25 The prognosis in Severe Dengue [ DHF / DSS ] Depends on Prevention or early recognition and treatment of shock. In hospitals with long experience of DSS the case fatality rate in DHF can be as low as 0 2%. Once shock has set in the fatality rate may be high (12% to 44%).

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28 Study design Retrospective, multiple-center, observational study, Retrieved the medical files from all adult patients (> 15 years) with a diagnosis of DHF or DSS and with a positive immunoglobulin (Ig) M test result for dengue Admitted to the intensive care units (ICUs) of Pune, India, Prayag Hospital, Niramaya Hospital, Deenanath Mangeshkar Hospital between January 1, 2007 and December 31, 2008.

29 Data Collection Demographics Co morbidities Duration of fever Daily till discharge : Clinical signs Lab data X Ray Chest Microbiological SAPS II score Daily SOFA daily for 6 organs Total SOFA daily Fluid balance Amount and type of fluid Urine output Use of RRT Dose of vasopressors

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33 Lab values at admission to ICU

34 Lab values during ICU stay

35 Fluid balance Cumulative fluid balance over 72 hrs of ICU stay P < 0.05 Survivors Non survivors Hours after ICU admission

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37 Evolution of organ failures over first 5 days CARDIOVASCULAR HEPATIC RESPIRATORY

38 Evolution of organ failure over first 5 days RENAL CNS

39 Evolution of organ failures over first 5 days HEPATIC COAGULATION

40 Limitations Restrospective Missing Data? Diagnostic reliability of IgM Different fluid resuscitation protocols in different ICUs?

41 Conclusions Mortality ~ 19% Significant difference in the Hemodynamic, CNS and Respiratory Failures in the fatal vs. non fatal groups No difference in hematological manifestations We should focus our attention onto the hemodynamics

42 Conclusions II Cumulative fluid balance higher in fatal group Development of shock more after admission than on admission between survivors and non survivors Although aggressive fluid management may be the norm in the initial phase, we need to observe our strategies for continued fluid administration after the initial resusc phase

43 DIMODS study Conclusions Presence of Non Hematological Organ Dysfunction at ICU admission is associated with 29.1% mortality Higher SOFA score on ICU admission is associated with higher mortality Respiratory SOFA score 2 on ICU admission is an independent predictor of mortality.

44 DIMODS study Conclusions No relation with outcome Platelet count platelet transfusion Use of steroids LVEF CKMB levels Hepatic dysfunction Cardiovascular SOFA score at ICU admission Renal SOFA score at ICU admission Hematocrit value at ICU admission Sr Albumin level at ICU admission RBC transfusion, Use of colloids for resuscitation

45 Characteristics of fatal vs. non fatal cases in adult dengue patients Significant [ p < 0.05 ] high incidence of Dengue shock, and ARF No difference in other findings like Hb, hematocrit,wbc counts, concurrent bacteremia, antibiotic use, GI bleed, thrombocytopenia and its extent [ seen in 100% of both groups ], Pleural effusions, Rhabdomyolysis etc. [ Lee IK et al Am J Trop Med Hyg : 2008, 79 :146 ]

46 Hemodynamic changes Echo study in 24 serologically proven patients The mechanism of decreased cardiac output during toxic stage of DHF is complex. Decreased preload Decreased LV performance, Possibly a subnormal heart rate response in some patients Intensive Care Med (2003) 29:

47 Cardiac involvement in Severe Dengue 99m Tc-pyrophosphate imaging was done in 4 patients and it was discontinued because no myocardial necrosis was detected. Five patients had ST and T changes in the ECG Radionuclide ventriculography, ECG and echocardiography revealed no abnormalities after 3 weeks of follow up and the EF was > 50% in all cases.. Acute reversible cardiac insult may be noticed in DHF / DSS and could be responsible for hypotension/shock seen in some of these patients. J. P. Wali, et al. International J Cardiol 1998: 64:31 36

48 Future Planned a study to characterise the hemodynamics better Measurement of CO, 2 D echo, Preload, EVLW,? Study of microcirculation in these patients to characterise the type of shock Later to study the efficacy of specific therapeutic agents in reversing these abnormalities

49 Warning signs of progression to severe disease abrupt change from fever to hypothermia, severe abdominal pain, prolonged vomiting, altered mental status (e.g., irritability, confusion, lethargy).

50 What should alert us? Dengue like illness Persistent Vomiting, Extreme lethargy, exhaustion, Bouts of giddiness Lab Raised hematocrit, Raised BUN Creat

51 ICU management Appropriately early admission Fluid resuscitation Crystalloids [?? and colloids ] Volumes End points Vasopressors / Inotropes Aggressive Organ function support renal, ventilation, platelets cardiac function Secondary infection

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53 Starch may be a preferable resuscitation fluid because of reactions to dextran Wills BA, et al. Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med. 2005;353(9):

54 April Hospitalized patients with severe dengue infection should be treated in dedicated highdependency units. In such circumstances, mortality of less than 1% is achievable among patients with shock, and the need for ventilatory support and intensive care is minimized.

55 Killer 100 Patients will have died of Severe Dengue during the 3 days of WORLD CONGRESS 2015