• Academic Achievement

• The winner of poster presentation , The 14th National Congress of PETRI, Samarinda 2008

• The winner of poster presentation, Bali International Travel medicine Conference, Bali 2012

• The 3rd winner of oral presentation. Integrated management of Dengue (Host, agent, vector), Surabaya 2016.

• The best oral free paper of International Symposium on Antimicrobial Agents and Resistance & International Interscience Conference on Infection and Chemotherapy, Busan-Korea, 2017

• The big five of Warmadewa SINTA Rank 2018

• Dosen berprestasi 2019 LLDIKTI VIII 2019

• The 2nd Best Original Article on Journal of Travel Medicine 2018 at Conference of International Society of Travel Medicine, Washington DC USA, 2019

• Grant Achievement

• The 2016 International Society of Travel Medicine Research Grant Award

• Hibah Disertasi Doktor, Dikti 2017

CURRICULUM VITAE

Personal Data

Name : Dr. dr. Dewa Ayu Putri Sri Masyeni, SpPD-KPTI,FINASIM

Place/DOB : Tabanan, 27 November 1965

Job : Senior Lecturer at FKIK Universitas Warmadewa

Position : Head of FKIK Warmadewa Travel Health Unit

Email : masyeniputu@yahoo.com

Formal education

Undergraduate : Medical School of Udayana University, 1984-1991

Postgraduate/Internist : Medical Shcool of Udayana University, 1998-2003

Consultant of tropical & infectious disease: Medical School of Udayana University,

2010-2014

Doctoral Program : Airlangga University, 2015- 2018

• Scientific publication

• Sri Masyeni, Susila Utama, Agus Somia, Raka Widiana, Tuti P. Merati. Factors Influence Bone Mineral Density in HIV Naïve Patients at Sanglah Hospital. Acta Medica Indonesiana 2013;45:175-179.

• Dewi Megawati, Sri Masyeni, Benekditus Yohan, et al., 2016. Dengue in Bali: clinical characteristics and Genetic Diversity of Circulating Dengue Viruses. Plos NTD 2017; 11(5): e0005483.

• Sri Masyeni, Hegard Sukmawati, Sri Agung A, Lila Paramasatiari, Agus Somia, Gede Kambayana, N Astika, Reny Duarsa. Diarrhea among international travelers in Bali-Indonesia: clinical and microbiological finding. Intern J Travel Med Glob Health, 2017:8

• S Masyeni, DG Budiyasa, SA Aryastuti, H Sukmawati, D Megawati, T Kotaki, SQ Khairunisa, Arijana, S Ueda, Nasronudin, M Kameoka. Mitochondrial DNA depletion among HIV-infected patients at Sanjiwani Hospital, Gianyar, Bali. Internat J Antimicrobial Agent, 2017;50, S82-S82

• Sri Masyeni, Hegard Sukmawati, Ayu Savitri Siskayani, Satya Dharmayanti, Kartika Sari. Antimicrobial susceptibility patern of pathogens isolated from various specimens in Denpasar-Bali: a two years retrospective study. Biomed Pharmacol J, 2018;11(1):493-502

• Sri Masyeni, Usman Hadi, Kuntaman, Yora Permata Dewi. Profiling of Microrna Expression within the Cells of Peripheral Blood Mononuclear after an Infection with Serotype-2 of Dengue Virus: Preliminary Study Biomedical and Pharmaceutical Journal 2018; 11(2), p. 923-927

• S Masyeni, U Hadi, Kuntaman, B Yohan, N I Margyaningsih and R T Sasmono. Detection of micro RNA has-let-7e in peripheral blood mononuclear cells infected with dengue virus serotype-2: preliminary study. IOP Conf Ser: Earth Environ. Sci,2018;125:012010 doi:10.1088/1755-1315/125/1/012010

• Siti Qamariyah Khairunisa, Sri Masyeni, Adiana Mutamsari Witaningrum, Muhammad Qushai Yunifiar M, Dwi Wahyu Indriati, Tomohiro Kotaki, ShuheiUeda, Dewa G. Budiyasa, Nasronudin, Masanori Kameoka.Genotypic characterization of Human Immunodeficiency Virus type-1 isolated in Bali, Indonesia in 2016. HIV AIDS Rev 2018;17,2:81-90. DOI:https://doi.org/10.5114/hivar.2018.76375

• Sri Masyeni , Sintya E, Megawati D, Sukmawati, et al. 2018. Evaluation of antiretroviral effect on mitochondrial DNA depletion among HIV-infection in Bali, Indonesia. HIV/AIDS-Palliative Care;10:140-50

• Sri Masyeni , Yohan B, Somia IKA, et al. 2018. Dengue infection in international travellers visiting Bali,Indonesia. J Travel Medicine;25(1):1-7 doi: 10.1093/jtm/tay061

• Darmana IMS, Rusni NW, Masyeni S. 2018. Correlation between total lymphocyte counts and CD4 among human immunodeficiency virus (HIV) patients. MATEC Web of Conference;197:07002 https://doi.org/10.1051/matecconf/201819707002

• Widhidewi NW, Masyeni S, Sukmawati H. 2018. Tumour Necrosis factor-Alpha Level among travellers contracted with dengue virus infection in Bali. MATEC Web of Conference;197:07005 https://doi.org/10.1051/matecconf/201819707005

• N P D Witari, S Masyeni, N W Rusni, K T Sumadewi, A E Pratiwi and P B Asih. Chloroquin and Sulfadoxine sensitive Plasmodium Falciparum in a Finland male

MANAGEMENT OF DENGUE SHOCK

SYNDROME

Dewa Ayu Putri Sri Masyeni

Bagian/SMF/Departemen Ilmu Penyakit Dalam

FKIK Universitas Warmadewa

RSUD Sanjiwani Gianyar

PETRI Bali

2019

Logo RumahSakit bila ada

4

INTRODUCTION

• Severe dengue: a leading cause of serious illness and death among children in Asian and Latin American countries.

• Severe dengue: first recognized in the 1950s during dengue epidemics in the Philippines and Thailand, CFR: 5-20%.

• There is no specific treatment BUT early detection and access to proper medical care lowers fatality rates below 1%.

• WHO: April 15, 2019, dengue situation update: Cambodia DENV mortality 5/392 (0.003%), Lao 6/1,752 (0.0034%), Malaysia 65/41,443 (0.0016), Philippines 237/59,139 (0.004), Spore 2,641, VietNam3/52,482 (0.00006), Australia 19 cases.

(WHO, 2019; https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue)Bhatt et al. 2013. Nature.;496:504-7)

Dengue cases distribution and dengue

severity 2015-2019 Sanjiwani Hospital Bali

• DSS: 0.003%- 0.005%

• CFR: 0.0003%- 0.05%

(Masyeni, unpublish data, 2019)

77 43 21 31 34

975

2454

24173

211168

656

30 3 533201

15 3 20

500

1000

1500

2000

2500

3000

2015 2016 2017 2018 2019

Chart Title

DF DHF Gr 1 DHF Gr 2 DSS DEATH

6 1 0 0 1

(Megawati et al. PloS NTD, 2017; 11(5): e0005483 )

• Among 154 samples successfully serotyped, the DENV-3 was predominant, followed by DENV-1, DENV-2, and DENV-4.

• SD: 0.002%

SEVERE DENGUE

• WHO 2009/2012:• SEVERE PLASMA LEAKAGE DSS/FLUID ACCUMULATION WITH RESPIRATORY

DISTRESS

• SEVERE BLEEDING

• SEVERE ORGAN IMPAIRMENT

Case

• A previously well 45-year-old Balinese male had a history of fever since 5 days PTA, followed with headache, muscle ache, & associated with vomiting and diarrhea over the last three days, @ 4 x a day.

• Vital sign: GCS 15, BP 110/95, temp 37.1⁰ C, PR 112 bpm, RR 24 bpm, sat: 99%.

• What do you have to evaluate?

• Any warning sign?

• Others emergency point?

Four important steps to assess the patient

Learning points & pitfalls

• Don’t missed the compensated dengue shock sign on admission• Altough the BP seemingly normal but PP was narrowing

• Accompanied with severe tachycardia in the absent of high temp.

• Don’t forget to touch the patient• Assessed the peripheral perfusion

Dengue Shock Syndrome

• HYPOVOLEMIC SHOCK, RESULTS OF CONTINUED VASCULAR PERMEABILITY & PLASMA LEAKAGE

• AROUND DEFERVESCENCE: 4-5 DAYS OF ILNESS (3-8)

• PRECEDES WITH WARNING SIGN

Timing of plasma leakage

What happens during the critical phase?

PEARLS:

RECOGNIZE THE DANGER SIGN!!

(SR Hadinegoro, 2019)

Haemodinamic assessment

(WHO, 2012)

• A previously well 45-year-old Balinese male had a history of fever since 5 days PTA, followed with headache, muscle ache, & associated with vomiting and diarrhea over the last three days, @ 4 x a day.

• Vital sign: GCS 15, BP 110/95, temp 37.1⁰ C, PR 112 bpm, RR 24 bpm, sat: 99%.

• Thoraks: po: VF ↓/ +, redup ICS V dextra

• Abdomen: hepar 2 cm bac, tajam, nyeri tekan (+)

• NS1 (+), WBC 2,07 HGB 16,3 HCT 48,9 PLT 37

• Assessement: ??

• Management?• Fluid?• Rate? Duration?• Monitoring?• Planning

CASE

Treatment of group C (severe dengue)

• Hospital admission, with access to blood transfusion

• Obtain HCT before & after fluid resuscitation & also blood group

• Isotonic crystalloid solution & sufficient volume

• Improving central & peripheral circulation

• Improving end-organ perfusion

Fluid in dengue

• No clear advantage to the use of colloids over crystalloids in terms of the overall outcome.

• Crystalloid: normal saline, ringer’s lactate, ringer’s acetate, ringers dextrose

• Colloid solution: preferred to use in hypotensive shock or failure of bolus crystalloid in decreasing HCT

• Colloids preferred :• Need to restored BP urgently, i.e. PP< 10 mmHg.

• Restore the cardiac index and reduce the level of hematocrit faster than crystalloids in patients with intractable shock

Colloid has faster effect :decreasing haematocrit &restoring cardiac indexthan crystalloid

Algorithm for fluid management of

compensated shock in adult

(WHO, 2012)(Handbook for clinical management of dengue.WHO-TDR,2012)

Case: a 68 y.o.man + CHD

March 25, March 26

March 27 March 28 March 29 March 30, 4 pm

Fever onset, take own PCT

First GP visitGCS 15, BP 130/80, PR 110 bpm, temp 40 C

Viral illness

Suggest: CBC

Vomited 5 x, abdominal pain,

2nͩd GP visitGCS 15, BP 110/95, PR 110 bpm, temp 37,2 C

Suggest: in patientPatient denied to hosp

admitted

ED: Vomiting 2x,

GCS lethargic, BP 80/-, PR absent, RR 24,

temp 36.7CBreath sound absent

infrascapular, hepatomegaly

Please add other finding!

NS1 (+), WBC 1,8, HGB 18,7 HCT

52,3 Plt 12, AST 389

ALT 467

• Assessment?• Management?• Where to treat?

• Duration of the fluid resuscitation?

Fever, mual, loss apetite

Algorithm for fluid management of hypotensive shock

(Handbook for clinical management of dengue.WHO-TDR,2012)

Laboratory investigations (ABCS) for profound shock

(WHO, Comprehensive guideline for prevention and control of dengue & DHF, 2011)

Additional data

Case: a 68 y.o.man with CHD

March 25, March 26

March 27 March 28 March 29 March 30, 4 pm March 30, 6 pm

Fever onset, anorexia, headache

Take own PCT

First GP visitGCS 15, BP 130/80, PR 110 bpm, temp 40 C

Viral illness

Suggest: CBC

Vomited 5 x, abdominal pain,

2nͩd GP visitGCS 15, BP 110/95, PR 110 bpm, temp 37,2 C

Suggest: in patientPatient denied to hosp

admitted

ED: Vomiting 2x,

GCS lethargic, BP 80/-, PR absent, RR 24,

temp 36.7CBreath sound absent

infrascapular, hepatomegaly

Please add other finding!

• Assessment?• Management?

GCS 10, BP 90/60, PR 110, CRT 12

WBC 7,4; HGB 13.4 HCT 40 PLT 11

NS1 (+), WBC 1,8, HGB 18,7 HCT

52,3 Plt 12, AST 389

ALT 467

Treatment of haemorrhagic complication

• Attempts to stop bleeding

• Replace blood loss: 5-10 ml/kg fresh PRC or 10-20 ml/kg fresh whole blood

• Consider repeating blood transfusion

• In the case of GI bleeding: H2 antagonist / PPI have been used

• NGT: great care, with over lubricated NGT

• CVP: ? need USG guidance

Risk of bleeding in dengue

• Have profound/prolonged/refractory shock

• Have hypotensive shock/MOF/severe and persistent metabolic acidosis

• Given NSAID

• Pre-existing peptic ulcer ds

• On oral anticoagulant therapy

• Have any form of trauma, including i.m injection

Any rule of platelet transfusion??

WHO

• There is no evidence support the practice of platelets transfusion and or FFP for severe bleeding in dengue

• They are not able to sustain of platelet count & coagulation profile

• Obstetrical deliveries or other surgeries: ?

CASE

Case: a 25.7 y.o Germany lady

January 14, January 15

January16

January 17 January 18,08.00 AM

Jan 18,2 pm

Jan 18, 6 pm Jan 19, 6 am, day 6 Jan 20, day 7 Jan 22 day 9

WARD:Epistaxis, gum

bleedingGCS 13, BP 100/90, PR 109 bpm, temp 37 C

ICU treatmentWBC 3.08 HGB 14.8,

HCT 43.6 PLT 9Management?

NS1 (+), WBC 3.5 HB 15.2, HCT 46.8, PLT 44

Management?

ED: GCS 15, BP 100/80, PR 80, RR 18, temp

36.7CBreath sound absent

infrascapular, hepar 1 cm bac, ascites +

Please suggest where to treat!

Fever onset, anorexia, retro

orbital pain, myalgia,

arthralgia, abundant,

stomach ache menstruation.Take own PCT

Treat as compensated shock!

Improved Vital sign2nd CBC:

WBC 3.8 HGB 14.7 HCT42.4 PLT 4Management?

ICU:Epistaxis, gum bleeding on off

GCS 15, BP 110/80, PR 94 bpm, temp 36 C

3rd CBCWBC 5.89 HGB 12.9, HCT 39.4.6 PLT 3

4th CBCWBC 5.28 HGB 13.4, HCT 37.8.6 PLT 2

Management?

Treat as compensated shock with maintenance fluid & TC 8 kolf

Vital sign stabil , no bledingWBC 5.71 HGB 12.8, HCT 36.5. PLT 11

6th CBC:12 am, WBC 4.73 HGB 13.1 HCT39.8

PLT 23USG PE +, Asc +, GB double layer,

heaptomegalyManagement?

ICUWARDNo bleeding

GCS 15, BP 115/80, PR 64 bpm, temp 36 C

CBCWBC 5.11 HGB 12.6, HCT 38.2.6 PLT 67

4th CBC

Management?

DischargeVital sign stabil

WBC 5.46 HGB 12.4, HCT 38.7 PLT 144

Advice?

Any rule of steroid in dengue?• Any rule of steroid in dengue??

WHO guideline

• No adjuvant with steroid, in the early or late phase of the ds, whether low dose nor high dose

• Despite the lack of convincing evidence of its benefit, trials of corticosteroid in dengue infection continue

• There was no evidence of significantly increased or prolonged viremia with prednisolone use,

• No effect of the intervention to hematologic & virological parameter

• DSS, significant bleeding, thrombocytopenia, and coa-gulopathy occurred with similar frequencies across all the groups

• Transient hyperglycaemia in high-dose steroid group

• The methodological quality and validity were poor, with high risk of bias and inadequate power

• This meta-analysis showed that these trials did not detect an effect • on death (4 trials, 284participants, very low quality evidence)• the need for blood transfusion (2 trials, 89 participants, very low quality evidence)• the development of complications such as shock (2 trials, 268 participants, very low

quality evidence)• severe bleeding (2 trials, 425 participants, very low quality evidence)• severe thrombocytopenia (1 trial, 225 participants, very low quality evidence)• duration of hospitalization (1 trial, 89 participants, very low quality evidence)

• Eleven cytokines (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70,IL-13, IFNc, TNFaand IP10) were quantified using a multiplex biometric immunoassay

• The gene expression microarray assay, and the procedures for normalization and analysis of the microarray

• Validation with PCR

• Differentially abundant gene expression linked to high-dose prednisolone therapy

• Steroid does not impact the IFN type 1 pathway

Others treatment in DSS

• Glucose control

• Electrolyte and acid base imbalances• Hyponatremia is common in dengue

• Isotonic solution will correct it

• Hyperkalemia due to metabolic acidosis or AKI

• Metabolic acidosis• Compensated metabolic acidosis is an early sign of hypovolemia /shock

• Due to lactic acidosis related with tissue hypoxia/hypoperfusion in shock

• Adequate fluid replacement is the key treatment

• Sodium bicarbonate is not recommended for pH ≥ 7.10

When to stop intravenous fluid therapy??

• Sign of cessation of plasma leakage

• Stable BP, pulse, and peripheral perfusion

• HCT decrease in the presence of good pulse volume

• Apyrexia (24-48 h) without PCT

• Resoving bowel or abdominal symptoms

• Improving urine output

Good VS Bad clinical practice

Summary

• The most outstanding pitfall in the clinical management of SSD is don’t miss the danger sign of early shock

• DSS precede by warning sign

• Comprehensive anamnesis, physical examination (touch the patient) at the ER may reduce morbidity & mortality of DSS

• Judicious volume replacement by iv therapy at early stage, may modify the ds severity.

• Frequent reassessing the patient with shock is mandatory

• No rule of prophylactic platelet transfusion nor steroid therapy in management of DSS

Terima Kasih

Calculation for normal maintenance of intravenous fluid infusion