guidelines on management of df and dhf in adults
TRANSCRIPT
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Ministry of Health - Sri Lanka
National
Guidelines
Guidelines on Management of Dengue Fever &Dengue Haemorrhagic Fever
In Adults
In Collaboration with theCeylon College of Physicians
December 2010
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Te guidelines, published in December 2010, supersede the previous guidelines onClinical Management o Dengue Fever / Dengue Haemorrhagic Fever published byEpidemiology Unit, Ministry o Health in 2005.
Tese guidelines were developed based on the best available evidence at the time owriting. It is expected to be used in the clinical management o dengue inection in
Sri Lanka. Te guidelines will be reviewed periodically when new evidence becomesavailable.
Please orward your comments and suggestions to the ollowing address by post or
e-mail.
Te EpidemiologistEpidemiology Unit
231, De Saram PlaceColombo -10
E-mail: [email protected]
Electronic version is available on
www.epid.gov.lk
ISBN 978-955-0505-12-8
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ContentsForeword v
Preace I vi
Preace II viiAcknowledgements viii
List o Contributors ix
1. Introduction 1
2. The Natural Course o the Illness 2
2.1 Febrile phase 3
2.2 Critical phase (leakage phase) 3
2.3 Convalescent phase (recovery phase) 4
3. Diagnosis at OPD Level & by the Primary Care Physician 6
4. Criteria or Admission 7
5. Management o those who Do Not Need Admission 8
6. Inward Patients 9
6.1 Introduction 9
6.2 Detection o critical phase (onset o plasma leakage) 9
6.3 Early detection o shock 9
6.4 Monitoring patients during hospital stay 10
6.5 Management o inward patients 12
6.6 Options o Fluid or Resuscitation 18
6.7 ABCS 18
6.8 Indications or Blood Transusion 19
6.9 Indications or Haemodynamic Support 20
7. Management o Hepatitis and Hepatic Encephalopathy in DHF 21
8. Dengue in Pregnancy 22
8.1 Management o pregnant patients with DF/DHF close to delivery 22
9. Myocardial Involvement in Dengue 23
10. Place o Adjunctive Therapy in the Management o DHF 24
10.1 Platelet transusion 24
10.2 Fresh rozen plasma transusion 24
10.3 Steroids and I.V. immunoglobulin 24
10.4 Recombinant Factor VII 24
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10.5 Antibiotics 25
10.6 Frusemide 25
10.7 Tranexamic acid 25
11. Transerring a patient to another Institute 26
12. Discharge 27
13. Laboratory Diagnosis 28
14. Outbreak Response Plan or Hospitals 29
Annexures 31
Monitoring chart during pre-critical phase 31
Monitoring chart during critical phase 32
Reerences 33
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v
Foreword
Dengue haemorrhagic ever (DHF) has become a major public health problemin Sri Lanka in recent years. A large number o suspected Dengue ever (DF) andDHF patients are seen at both out-patient departments as well as at inward levels inmost hospitals in the country regularly. Te number o deaths due to dengue showan upward trend despite the case atality rate remaining under 1% probably dueto the high case load used as the denominator. Tereore, a thorough evaluationo the clinical management could reduce the mortality urther due to this disease.
I hope that these guidelines on clinical management o dengue ever and denguehaemorrhagic ever prepared by the Epidemiology Unit in collaboration with theCeylon College o Physicians will be a vital tool or all clinical practitioners inorder to urther strengthen clinical management.
Dr. Ravindra Ruberu
SecretaryMinistry of Health
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Preace I
Dengue Fever (DF) is currently the most important mosquito-borne viral inectiono public health signifcance in Sri Lanka, with thousands o patients acquiring theinection each year. During the Last two to three years we have witnessed hyper-endemicity with more severe maniestations such as Dengue Haemorrhagic Fever(DHF) and Dengue Shock Syndrome (DSS) leading to considerable morbidity andmortality with a signifcantly high case atality rate.
Tese guidelines on clinical management o dengue ever have been developedby a team o physicians who are experienced in the feld, in consultation withthe Ceylon College o Physicians. Tis document is intended to provide guidanceor physicians and all categories o doctors to carry out appropriate treatment orpatients with Dengue Fever/Dengue Haemorrhagic Fever and would help to bring
down complications and the case atality rate to a minimum in the uture.
Dr. Kamani WanigasuriyaPresidentCeylon College of Physicians
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Preace II
Dengue inection has become the most important communicable disease in SriLanka today with a signifcant social, economic and political impact. Recent den-gue epidemics were reportedly more severe. Nevertheless, it is observed that theknowledge on clinical management o dengue has improved tremendously overthe past ew years.
In act, the World Health Organization (WHO-SEAR) is in the process o devel-oping new Comprehensive Guidelines or Prevention and Control o Dengue &DHF - 2nd Edition, 2010. In keeping with the new developments, the Ministry oHealth invited a group o specialists to develop resh guidelines on clinical man-agement o Dengue Fever & Dengue Haemorrhagic Fever with a view to using itas an authoritative source o reerence by all levels o health proessionals. Tis
document is intended to expeditiously disseminate and establish new knowledgeat all levels o the healthcare services and thereby contribute signifcantly to reducemorbidity and prevent mortality associated with this disease.
I would like to acknowledge the eorts o all those who contributed to this docu-ment and wish to thank each and every one o them.Appreciation is extended to the WHO or their assistance in providing unds orthis publication.
Dr. Sudath Peiris
Acting Chief Epidemiologist
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Acknowledgements
Appreciation is extended to the World Health Organization or the continuedtechnical collaboration, and unding provided or the training o health sta andor the printing o this document. We acknowledge the guidance given by Dr. F. R.Mehta, WHO Representative to Sri Lanka and the support extended by Dr. SupriyaWarusawithana, National Proessional Ocer and all sta at the WHO oce in SriLanka.
We greatly appreciate the sharing o experience and the guidance o ProessorSiripen Kalyanroogh and her team at the WHO Collaborating Centre or CaseManagement o Dengue/DHF/DSS, QSNICH, Bangkok, Tailand.
Special thanks are due to the ollowing individuals or their contributions and
comments in the preparation o these guidelines at dierent stages Dr. Lak KumarFernado, Consultant Paediatrician, General Hospital Gampaha, Dr. Sunethra Gu-nasena, Consultant Virologist - MRI, Dr. Rasnayaka Mudiyanse, Senior Lecturerin Paediatrics, Faculty o Medicine, Peradeniya, Dr. Kapila Gunawardane, SeniorLecturer in Obstetrics & Gynaecology, Faculty o Medicine Peradeniya, Dr. N. M.M. Navaratne, Consultant Gastroenterologist - NHSL, Dr. Udaya Karunarathne,Consultant Anaesthetist, General Hospital Matara, Dr. J. S. D. K. Weeraman, Con-sultant PaediatricianDr. NihalAbeysinghe, ormer Chie Epide.
Guidelines Development Committee
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List o Contributors
X Guidelines Development Committee
y Dr. Nirmalee Gunawardane
Consultant Physician - eaching Hospital, Kandy
y Dr. Ananda Wijewickrama
Consultant Physician - Inectious Diseases Hospital, Colombo
y Dr. Upul Dissanayake
Consultant Physician - District General Hospital, Kalutara
y Dr. Kolitha Sellahewa
Consultant Physician to the Epidemiology Unit
y Dr. Hasitha Tissera
Consultant Epidemiologist, Epidemiology Unit
X Editorial Assistance
y Dr. Pradeep Wijayagoonawardana
Registrar in Medicine, Sri Jayewardenepura General Hospital
X The following reviewers provided their comments on behalf of the Ceylon College of Physicians
y Dr. Kamani Wanigasuriya
Senior Lecturer - Faculty o Medical Sciences, University o Sri Jayewardenepura
President - Ceylon College o Physicians 2010/11
y Dr. Sarath Gamini de Silva
Consultant Physician
y Dr. Chandani Wanigatunga
Senior Lecturer - Faculty o Medical Sciences, University o Sri Jayewardenepura
X The following external reviewers provided their comments on the draft
y Pro. Siripen Kalyanrooj
Director - WHO Collaborating Centre o case management o DF/DHF/DSSQSNICH, Bangkok, Tailand
y Dr. Pra-on Supradish
Consultant - WHO Collaborating Centre o case management o DF/DHF/DSSQSNICH, Bangkok, Tailand
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1. Introduction
Te course o dengue inection varies rom individual to individual and even in thesame individual rom time to time. Tis guideline includes new concepts, based onscientifc evidence, on the management o Dengue Fever (DF) and Dengue Haem-orrhagic Fever (DHF). It emphasizes the early detection o plasma leakage andprevention o shock, early detection o shock, treatment o shock, management ospecial situations and the place or adjunctive treatment in patients with Dengue.
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2. The Natural Course o the IllnessMany patients inected with dengue virus remain asymptomatic. Others, aer anincubation period o 4-7 (range 3-14) days, develop a ebrile illness which couldturn out to be one o ollowing.
y Undiferentiated ebrile illness
y Dengue ever (DF)
y Dengue Haemorrhagic Fever (DHF)
Undierentiated ebrile illness and classical dengue ever can be managed as anyother viral ever with symptomatic treatment. However, oen it is dicult to di-erentiate DF rom DHF in the early phase (ebrile phase) o the illness.
Tereore suspected DF and DHF patients should be closely monitored to identiypatients with DHF. It is the patients with DHF who develop plasma leakage andresultant complications.
Patients with dengue ever can sometimes develop unusual maniestations such asmassive bleeding, hepatitis and encephalitis without evidence o uid leakage and
thereore do not all into the category o DHF. Tese conditions are very rare andmanagement o these conditions is symptomatic.
Dengue Viral Inection
Asymptomatic Symptomatic
Dengue Fever
(DF)
Undiferentiated
Febrile IllnessDengue Haemorrhagic Fever
The hallmark o DHF is plasma leakage
Non Shock.
(DHF Grades 1 & 2)
Shock.
(DHF Grade 3 & 4)
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For ecient management o DHF it is important to understand its natural historyand its dynamic nature. Clinical course o DHF consists o three stages
y Febrile phase
y Critical phase (leakage phase)
y Convalescent phase
2.1 Febrile phase
Febrile phase is characterized by continuing high ever lasting 2-7 days. Othereatures seen in the ebrile phase include acial ushing, skin erythema, myalgia,arthralgia, headache, nausea and vomiting. Some patients may have sore throat,injected pharynx, conjunctival injection and diarrhoea. Mild haemorrhagic mani-estations can occur. Leucopenia (WBC
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Other evidence o plasma leakage are a decrease in serum albumin (
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y Haemodynamic stability
y Bradycardia (seen in some patients )
y Diuresis
y Stabilization o Haematocrit (HCT may even be lower than baseline due to reab-
sorption o extravasated uid)
y Rise in white cell count ollowed by a rise in the platelet count.
However, i excessive amounts o intravenous uids have been used in the criticalphase there could be signs o uid overload such as respiratory distress due topulmonary oedema or large pleural eusions.
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3. Diagnosis at OPD Level & by the Primary Care Physician
In the present hyper-endemic setting in Sri Lanka, dengue ever should be consid-ered in the dierential diagnosis o patients presenting with acute onset o everwith two or more o the ollowing:
y Headache, especially retro-orbital pain
y Myalgia /Arthralgia
y Rash (difuse, erythematous, macular)
y Haemorrhagic maniestation (petechiae, positive tourniquet test etc.)
y Leukopenia (< 5000 /mm3)
y Rising haematocrit o 5 - 10 %
y Platelet count 150,000 /mm3
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4. Criteria or Admission
Te frst contact physician may decide to admit a patient on clinical judgment.
However it is essential to admit patients:
X With platelet count less than 100,000/mm3
X With the ollowing warning signs :
y Abdominal pain or tenderness
y Persistent vomiting
y Clinical signs o plasma leakage: pleural efusion, ascites
y Mucosal bleeding
y Lethargy, restlessness
y Liver enlargement >2 cm
y Increase in haematocrit (HCT) concurrent with rapid decrease in platelet
count in a Full Blood Count (FBC)
Other patients who may need admission even without above criteria are:
y Pregnant mothers
y
Elderly patientsy Obese patients
y Patients with co-morbid conditions like diabetes, chronic renal ailure, ischae-
mic heart disease, thalassaemia and other haemoglobinopathies and other
major medical problems
y Patients with adverse social circumstances- e.g. living alone, living ar rom
health acility without reliable means o transport.
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5. Management o those who Do Not Need Admission
Ensure adequate oral uid intake o around 2500 ml or 24 hours. Tis shouldconsist o oral rehydration uid, king coconut water, other ruit juices, kanji orsoup rather than plain water. Exclude red and brown drinks which could causeconusion with haematemesis or coee ground vomitus.
Following treatment measures are recommended :
y Adequate physical rest
y Tepid sponging or ever
y Paracetamol not exceeding 2 tablets six hourly (reduce dose or patients with
lower body weights). Warn the patient that the ever may not ully settle with
paracetamol, but not to take excess.y Anti emetics and H
2receptor blockers i necessary
y Avoid all NSAIDS and steroids
y Withhold Aspirin, Clopidogrel & Dipyridamole in patients who take these on
long term basis
y Review daily. A ull blood count should be done at least on the third day o
illness. (A ull blood count should be done on the rst day o ever in pregnant
patients and in patients with chronic renal ailure)y Advise immediate return or review i any o the ollowing occur:
y Clinical deterioration with settling o ever
y Inability to tolerate oral uid
y Severe abdominal pain
y Cold and clammy extremities
y Lethargy or irritability/restlessness
y Bleeding tendency including intermenstrual bleeding or menorrhagia
y Not passing urine or more than 6 hours
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6. Inward Patients
6.1 Introduction
Inward patients include patients with DF and patients with DHF. Dierentiationbetween these two is dicult during initial ew days (frst three to our days oever).
Te hallmark o DHF is plasma leakage. Tis is not present in DF. Plasma leakageis the main cause or shock, subsequent bleeding, organ ailure and death.
Te only way o diagnosing a patient with DHF clinically is the detection o plasmaleakage.
Tereore the mainstay o inward care is
X Early detection o plasma leakage (onset o critical phase)
X Judicious fuid management to prevent shock and to prevent fuid overload
6.2 Detection o critical phase (onset o plasma leakage)
A white cell count o 5000/mm3 or less with predominance o lymphocytes and aplatelet count less than 100,000/mm3 may indicate that the patient is in danger ogoing into critical phase within the next 24 to 48 hours.
A progressively rising haematocrit, even beore reaching a rise o 20%, with othereatures such as tender hepatomegaly may indicate that the patient is entering thecritical period.
Presence opleural efusion and ascites indicate that the patient is already in the
critical phase. Pleural eusion detected clinically may not be obvious in a CXR-PA,but may be seen only in a CXR right lateral decubitus flm. I appropriate interven-tions are not adopted early the patient may develop shock.
6.3 Early detection o shock
Prevention or early treatment o shock is essential i complications are to beavoided.
o detect shock early, observation or ollowing symptoms and signs is important.Hence maintenance o monitoring charts which help to detect early symptoms
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and signs o shock is important in the management o DF/DHF. Please reer toannexures or the charts.
Symptoms o Shock
X Sweating
X Abdominal pain
X Persistent vomiting
X Restlessness / altered conscious level
X Postural dizziness
X Decreased urine output (2 seconds
X Unexplained tachycardia
X Tender hepatomegaly >2 cm
X Increasing diastolic pressure
X Narrowing o pulse pressure 20 mmHg
X Postural drop 20 mmHg o systolic blood pressure
X Hypotension (rom patients baseline)
6.4 Monitoring patients during hospital stay
6.4.1 I the patient is clinically stable on admission and DF/DHF is suspected
y Chart temperature 4 hourly
y
Watch or evidence o bleeding specially malena or bleeding per vaginay Assess vital signs
y Do a ull blood count on admission and then daily
6.4.2 When platelet count drops below 100,000/mm3
Start monitoring using the monitoring chart 1.
X The purpose o this monitoring is to detect entry into the critical phase.
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Monitor,
y Temperature our hourly
y Vital parameters- pulse, blood pressure (both systolic and diastolic), respiratory
rate, and capillary rell time-our hourly
y Detailed uid balance with:
i Intake with type and route o uid assess six hourly
i Output urine/vomitus - assess six hourly
i FBC daily
i HCT twice daily
6.4.3 When the patient enters into critical phase (leakage phase)
Start monitoring using the monitoring chart 2.
X The purpose o maintaining this monitoring chart is or accurate uid man-
agement and early detection o shock.
Entry into critical phase is indicated by evidence o plasma leakage and more re-quent monitoring is now necessary.
Monitor,y Vital parameters- hourly
y Fluid balance chart- assess three hourly
y HCT- six hourly
in addition to monitoring other parameters mentioned in 6.4.2
6.4.4 I there is evidence o shock (compensated or uncompensated shock)
Vital parameters should be checked every 15 minutes till the patient is haemo-dynamically stable. During intense uid resuscitation HC should be checkedimmediately beore and aer each uid bolus and then at least two to our hourly.
X I the shock is prolonged (not responding to initial uid bolus) an indwell-
ing urinary catheter should be inserted and urine output should be measured
hourly. Due to uid extravasation leading to a relative reduction in intravascular
volume, the urine output (UOP) is likely to be less than normal. Hence, a UOP o
0.5 ml to 1 ml/kg BW/ hour is adequate during this period. Overenthusiastic uid
replacement to achieve a higher UOP may lead to uid overload.
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Liver profle, blood sugar, serum calcium, serum electrolytes, serum creatinine,clotting profle and venous blood gases should be done in complicated cases suchas prolonged shock, not responding to adequate uid resuscitation, liver ailureand renal ailure.
6.4.5 In convalescent phase
Watch or symptoms and signs o uid overload such as cough, wheeze andtachypnoea, rise o both systolic and diastolic blood pressures, basal crepitationsand rhonchi. Urine output is usually high during this phase. Some patients maydevelop bradycardia which is usually asymptomatic and transient.
6.5 Management o inward patients
6.5.1 Febrile phase with platelet count more than 100,000/mm3
Management o this phase is essentially similar to outpatient management exceptor the addition o intravenous uids. Intravenous uids (I.V.) may be indicated inpatients who are unable to take orally, or in patients with diarrhoea or vomiting.
ype o I.V. uid should be Normal Saline or Hartmanns solution. Te totalamount o uid (both I.V. and oral) should be limited to 2500 ml or 24 hours oran average adult (2 ml/Kg/hr up-to a maximum o 50 Kg o weight).
However, i there is vomiting or diarrhoea this amount should be increased ac-cordingly.
X It should be emphasized that over hydration during this phase will not
prevent patients developing shock in critical phase. In act it may cause uid
overload during critical phase.
6.5.2 When the platelet count drops below 100,000/mm3
Insert a 18 G (green) cannula and start a slow intravenous inusion o Hartmannssolution or normal saline to keep vein open (1000 ml may be given over 24 hours).
X However the total (both oral and I.V.) amount o uid intake should not
exceed 2500 ml or an average adult unless the patient has vomiting or diar-
rhoea.
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6.5.3 When the patient is in the critical phase
otal uid requirement, both oral and intravenous, in critical phase (48 hours)is calculated as M+5% (maintenance + 5% decit)Maintenance (M) is calculated as ollows
For the 1st 10 kg - 100 ml /kg
For the 2nd 10 kg - 50 ml/kg
From 20 kg and above up to 50 kg - 20 ml/kg
5% decit is calculated as 50 ml/kg up to 50 kg
Example o fuid calculation or a 65 kg person (maximum body weight or fuidcalculation is 50 kg)
For the 1st 10 kg - 100 ml/kg = 1000 ml
For the 2nd 10 kg - 50 ml/kg = 500 ml
From 20 kg and above up to 50 kg -20 ml/kg = 600 ml
5% decit is calculated as 50 ml/kg up to 50 kg = 2500 ml
X Thereore the total uid requirement or an average adult or the entire
phase o critical 48 hours is 4600 ml.
I the body weight is less than 50 kg, calculation should be done according to theideal body weight or actual body weight whichever is less.
Te recommended intravenous uid is normal saline or Hartmanns solution.Oral uids should consist o electrolyte solutions such as king coconut water, otherruit juices, oral rehydration uid and kanji. Drinking o plain water should beactively discouraged.
How this volume should be inused during the critical period depends on the
haemodynamic status o the patient.
I the patient is haemodynamically stable (non-shock), but in critical (leaking)phase this volume (M+5) could be spread over 48 hours. However this volumeshould not be given at a uniorm rate. Te volume given should be just sucient tomaintain an eective circulation during the period o plasma leakage as too muchuid could lead to uid overload.
In keeping with the dynamic nature o the leakage, uid should be started at a
slower rate, or example 50-75 ml/hour (1-1.5 ml/kg body weight/hour).
Te rate o uid should be increased in a step wise pattern, according to the rise
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o HC and/or reduction o urine output below 0.5 ml/kg/hour, or example to arate o 150 ml/hour (3 ml/kg/hour). Since the plasma leakage does not persist ata higher rate or more than a ew hours, it is necessary to reduce the rate o uidintake in a step wise pattern again.
6.5.4 I the patient goes into shock while in the ward or i a patient presentswith shock
A blood sample should be collected or measurement o HC as soon as possible.
X IV uid should be started as a bolus. Usually with this the blood pressure and
the peripheral circulation improves. Since the uid leakage continues at a
high rate during this period it should be matched by a high inusion rate o
intravenous uids. Thereore, the uid bolus should be ollowed by high initial
rate o I.V. uid, which should be reduced gradually in a step wise manner.
X I the initial HCT is low or normal the shock is due to signicant concealed
haemorrhage in addition to plasma leakage. Thereore such patients need
urgent blood transusion.
Te initial rate o uid replacement depends on whether the patient is in shock
with narrow pulse pressure and/or hypotension or in proound shock with un-recordable blood pressure (Reer ow algorithms).
X The rate o I.V. uid given should be adjusted according to the pulse pres-
sure, capillary rell time, urine output and HCT.
Te amount o uid given during and aer shock depends on how much the pa-tient has received prior to onset o shock in the critical phase. I the patient hasbeen managed in the hospital and the onset o critical phase has been identifed the
volume o uid already given would be known.
In a patient who arrives rom home or transerred rom another institution andound to be in shock on admission, every eort should be taken to fnd out howmuch uid was given during the preceding 12-24 hours. Tis is because the criticalphase would have started 12-24 hours prior to the detection o shock in such apatient. Tis uid amount should be subtracted rom M+5% and only the balanceamount o uid should be given or the next 24 hours.
X Hence, it is important or all transerred patients rom smaller hospitals to
have this inormation clearly mentioned in the Transer Forms
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SHOCK WITH NARROW PULSE PRESSURE & HYPOTENSION
Fluid resuscitation with isotonic crystalloid 7- 10 ml/kg (350-500ml)* over 1 hour
(Try to obtain a haematocrit before fluid resuscitation)
Crystalloid 7 ml/kg (350ml) for 1 hour,then continue with:
IV crystalloid 5 ml/kg/hr for 1- 2 hours;
reduce to 3 ml/kg/hr for 2 - 4 hours; reduce to 1.5 ml/kg/hr for 2 - 6 hours.
If patient continues to improve, fluid can
be further reduced.
Monitor HCT 4 - 6 hourly
Administer 2nd bolus fluid
(crystalloid)
7-10 ml/kg (350-500ml) over 1 hour
Administer next fluid bolus
(colloid)
10 ml/kg over 1 hour
(Correct ABCS )
Improvement
HCT h HCT i or Normal
Consider significant
occult/overt bleeding
Initiate blood
transfusion
(1 unit at a time if blood
loss can not be
estimated)
Improvement
HCT h HCT i
or Normal
Yes No
Repeat HCT
Improvement
No
Yes No
Check ABCS
A - Acidosis B - Bleeding C- Calcium S - Sugar
Yes
* In the elderly and in patients with heart disease & renal disease consider using lower infusion rates.
Review HCT
Algorithm 1
( max. 500 ml per bolus)
SHOCK WITH NARROW PULSE PRESSURE & HYPOTENSION
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PROFOUND SHOCK
Fluid resuscitation with 10 ml/kg (500ml) isotonic crystalloid over 15 minutes
(Try to obtain a haematocrit before fluid resuscitation)
Crystalloid 10 ml/kg (500ml) for 1 hour,then continue with:
IV crystalloid 7 ml/kg/hr for 1- 2 hours;
IV crystalloid 5 ml/kg/hr for 1- 2 hours; reduce to 3 ml/kg/hr for 2 - 4 hours;
reduce to 1.5 ml/kg/hr for 2 - 6 hours.
If patient continues to improve, fluid can
be further reduced.
Monitor HCT 4 - 6 hourly
Administer 2nd bolus fluid
(crystalloid)
10 ml/kg (500ml) over 1 hour
Administer next fluid bolus
(colloid)
10 ml/kg over 1 hour
(Correct ABCS )
Improvement
HCT h HCT i or Normal
Consider significant
occult/overt bleeding
Initiate blood
transfusion
(1 unit at a time if blood
loss can not be
estimated)
Improvement
HCT h HCTi
or Normal
Review HCT
Yes No
Repeat HCT
Improvement
No
Yes No
Check ABCS
A - Acidosis B - Bleeding C- Calcium S - Sugar
Yes
Algorithm 2
(max . 500 ml per bolus)
PROFOUND SHOCK (UN-RECORDABLE BLOOD PRESSURE)
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6.5.5 Fluid over-loaded patient
A patient may become over-loaded with uid while in the ward or may be trans-erred rom another unit in an over-loaded state due to over-enthusiastic treat-ment with I.V. uid (too much oral uid also can contribute to this). Hypotension
and moderately high HC due to dehydration (in the ebrile phase) may lead tothe misdiagnosis o shock in critical phase and uid resuscitation o such situationalso may lead to over-hydration.
Fluid over-loading should be treated according to the haemodynamic status andthe HC o the patient.
X I the patient is in shock or has eatures o pulmonary oedema and has high
HCT, a bolus o colloid (dextran 40 or Tetrastarch) should be given as 10 ml/
kg (500 ml or an average adult) over an hour. In the midway o the bolus,
rusemide 1 mg/kg should be given.
X I the patient is in shock and has a normal or low HCT, immediate blood
transusion is necessary. In the midway o the transusion, rusemide 1 mg/
kg should be given. Until blood is available, a bolus o colloid (300-400 ml o
Dextran 40 or Tetrastarch) could be administered.
X I the patient is haemodynamically stable and has high HCT, uid should be
restricted and patient should be monitored careully. It is likely that the pa-
tient will go into polyuric phase and the HCT will settle within several hours.
X I the patient is haemodynamically stable and has a normal or low HCT,
uid should be restricted and patient should be monitored careully, as the
patient is likely to improve within hours. The most probable reason or lowhaematocrit is haemodilution. I the patient develops eatures o pulmonary
oedema, rusemide 0.5 mg/kg should be given intravenously. This dose can
be repeated ater hal an hour.
Fluid over-load will worsen the uid extravasation. Tis may result in large pleuraleusions and severe ascites. Usually these settle with colloid boluses. However, thepleural eusion may rarely be big enough to interere with ventilation and mayneed to be drained out in addition to giving colloids.Rarely, severe ascites can cause abdominal compartment syndrome. (I the abdo-
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men is very tense even without distension, suspect this). Drainage o ascitic uid,in addition to transusion o colloids, may be indicated i this causes impairmento venous return or intererence with renal unction.6.6 Options o Fluid or Resuscitation
6.6.1 Crystalloids:
Normal saline or Hartmanns solution, should be used or initial uid resuscitation
6.6.2 Colloids:
Only hyper-oncotic colloids are eective. Tey are used only as boluses o 10 ml/kg/hour. Dextran 40 or etrastarch (6% starch solution) can be used :
y In patients who present in shock and uid overload
y In patients whose shock does not respond to two boluses o crystalloids with
rising HCT or still high HCT
y In patients who are being treated or shock, and has high HCT and whose uid
quota (M+5%) in nearing completion
As dextran can sometimes interere with cross matching, blood should be drawn
or grouping and cross matching beore starting on dextran. Te maximumamount o dextran or 24 hours is 3 boluses o 500 ml/hour (10 ml/kg/hour). Temaximum o etrastarch is 5 boluses o 500 ml/hour (10 ml/kg/hour) in 24 hours.
X Note: colloids should not be used in a dehydrated patient who presents with
shock and high HCT, until the hydration is corrected with crystalloid
6.7 ABCS
I the patient is not responding to two boluses o crystalloid, contributory causesor shock other than plasma leakage should be considered. Tese are,
X Acidosis-check venous blood gas (i present, check liver and renal proles)
X Bleeding- check HCT
X Calcium and other electrolytes (sodium and potassium) - check serum
X Sugar-check random capillary blood sugar
It is important to correct these conditions as quickly as possible. Tereore empiri-
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cal treatment with 10% calcium gluconate 10 ml over 10 minutes is justifable i apatient in shock is not responding to adequate uid replacement, and this may becontinued six hourly.
I.V. calcium gluconate may be used in patients who show evidence o myocarditis
as well, as hypocalcaemia is common in DHF grade I.V. patients and calcium mayimprove the myocardial contractility in such patients.
y I the patient is clinically acidotic one dose o 8.4% sodium bicarbonate 50 ml
may be given empirically i blood gas cannot be assessed.
y Correct the blood glucose i it is less than 60 mg/dl
6.8 Indications or Blood Transusion
Signifcant bleeding in DHF is usually due to DIC and liver ailure which occur asa consequence o prolonged shock causing multi-organ dysunction. Bleeding, ioccurring during the early phase o DHF, is usually due to drugs, such as NSAIDS.
Even without these causes bleeding can occur during the critical period and can bethe main reason or shock or contribute to development o shock.
I there is signifcant overt bleeding (e.g. haematemesis, malena, bleeding pervagina etc.) o more than 6-8 ml/kg body weight, blood transusion is necessary.
However, bleeding could be concealed. Suspect signifcant occult bleeding in theollowing situations and transuse blood:
X Haematocrit not as high as expected or the degree o shock to be explained
by plasma leakage alone. (Hypotensive shock with low or normal HCT)
X A drop in HCT without clinical improvement despite adequate uid replace-
ment (40-60 ml/kg).
X Severe metabolic acidosis and end-organ dysunction despite adequate
uid replacement.
(Note: that the haemoglobin level may remain normal initially despite signifcantblood loss.)
5 ml/kg o packed red cells (preerred in over-hydrated patients and in patients
with heart disease) or 10 ml/kg o whole blood can be given at a time. HC isexpected to rise by 5 points (e.g. rom 30 to 35) with this amount o blood.
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6.9 Indications or Haemodynamic Support
In dengue, hypotension is usually due to plasma leakage or internal bleeding. Fluidresuscitation is crucial and should be initiated frst. However, vasopressors (e.g.dopamine and noradrenaline) may be considered when the mean arterial pres-
sure is persistently
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7. Management o Hepatitis and Hepatic Encephalopathy in
DHF
Mild to moderate rise o liver enzymes (SGO, SGP) is a common fnding inDF and in DHF. Tis does not warrant any specifc treatment. Higher rise o liver
enzymes is usually due to ischemic hepatitis caused by prolonged shock. I thereare no eatures o hepatic encephalopathy, no specifc treatment is indicated inthese patients. I there are eatures o encephalopathy (with or without eatures ocoagulopathy) such patients should be treated as or liver ailure with the ollow-ing:
y Maintain adequate airway and oxygenation
y Inuse minimal intravenous uids sucient to maintain intravascular volume
(70 ml/hour)
y Use hyper-oncotic colloid solution early i HCT is increased
y Inuse Mannitol to reduce intracranial pressure i renal unctions are normal
y Take measures to maintain serum sodium in-between 145 -155 meq/L. (3% hy-
pertonic saline may be o use i Mannitol cannot be used, and i serum sodium
is very low)
y Maintain blood sugar above 60 mg/dl
y Give a single dose o Vitamin K 10 mg I.V.
y Give Lactulose to maintain 1 -2 bowel motions per day. However, lactulose
commonly causes gaseous abdominal distension and this may interere with
respiration in these patients and may even cause aspiration
y Treat with broad spectrum antibiotics, which are not excreted through liver, i
secondary bacterial inection is suspected (Ceotaxime is preerred)
y Oral Metronidazole may be used (supportive evidence is limited)
y
Ventilate (IPPV) early, i the eatures o encephalopathy are getting worsei Fresh Frozen Plasma (FFP) should not be used routinely, but may be used i there
is active bleeding or prior to invasive procedures. (However be aware o possible
fuid overload with FFP)
i Bowel washes and enemas should be avoided
Tere is no evidence to support the use o L- Arginine L-Ornithine (LOLA) orN-Acetyl Cysteine (NAC) in these patients and thereore, use o which is not rec-
ommended.
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8. Dengue in Pregnancy
X Early admission and close ollow up with FBC daily is very important
Te gestation and the phase o dengue are important actors in determining themanagement. Discussion with the team o obstetricians, physician and the pae-diatrician about the management is mandatory. Consultation and explanationwith the amily members about the course o DHF and the management are alsoimportant or decision making.
Tere are very ew studies addressing the management o dengue in pregnancy.Generally the presentation and clinical course o dengue in pregnant women issimilar to that in non-pregnant individuals. Te uid volume or the critical pe-riod (M+5%) or a pregnant mother should be calculated based on the weight
prior to pregnancy.
However, the signs and symptoms may be conused with other complicationso pregnancy such as toxaemia, Haemolysis, Elevated Liver Enzymes, Low
Platelets (HELLP) syndrome Tere are some reports o an increased incidenceo prematurity, in-utero death and abruptio placentae in these women
Te normal physiological changes in pregnancy make the diagnosis and assess-ment o plasma leakage dicult. Tereore ollowing baseline parameters should
be noted as early as possible preerably on the frst day o illness.
y Pulse, blood pressure (BP), pulse pressure. (Baseline BP is oten lower and pulse
pressure wider & heart rate may be higher)
y FBC - (Hb, HCT & platelet count may be lower than normal in pregnancy)
y SGOT/SGPT
Te detection o ascites and pleural eusions is dicult due to the presence ogravid uterus.
8.1 Management o pregnant patients with DF/DHF close to delivery
Risk o bleeding is at its highest during the period o plasma leakage (criticalphase). Tereore,
X I possible, avoid Lower Segment Caesarean Section (LSCS) or induction o
labour during critical (plasma leakage) phase.
X
Procedures/manoeuvres that may provoke or augment labour should beavoided during the critical phase
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9. Myocardial Involvement in Dengue
Global dysunction o myocardial contractility may be seen in DHF patients whoare in prolonged shock. Te most likely reason or this is metabolic acidosis.Hypocalcaemia, which is a common fnding in DHF grade III and IV, is anotherprobable cause.
X Hence, i there is evidence o cardiac dysunction, acidosis and hypocalcae-
mia should be corrected quickly
Empirical treatment is justifable i clinically indicated. Myocarditis is an uncom-mon fnding in Dengue and is very unlikely to cause death in a patient with DHF.However, such a patient could easily develop pulmonary oedema with uid over-
load.
X Thereore, i myocarditis is suspected uid should be given very careully
reatment o myocarditis is symptomatic.
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10. Place o Adjunctive Therapy in the Management o DHF
10.1 Platelet transusion
Prophylactic transusion with platelets does not produce sustained changes in thecoagulation status and platelet count in patients with DHF. It does not change orreduce the bleeding outcome in DHF either. On the other hand, platelet transu-sions can lead to uid overload resulting in pulmonary oedema and respiratoryembarrassment.
X Thereore, prophylactic transusion o platelets is not recommended.
However, platelet transusions may be required in a patient with thrombocytopeniawho is to undergo an urgent surgery, has active bleeding which continues in spite
o repeated blood transusions, DIC or in patients with intracranial haemorrhage.
10.2 Fresh rozen plasma transusion
Like platelet transusions, prophylactic FFP transusions do not produce sustainedchanges in the coagulation status, and thereore, does not change or reduce thebleeding outcome in patients with DHF/DSS. Like platelet transusions, FFP trans-usions can also lead to uid overload.
In addition, transusion o blood products can produce anaphylactic reactions andtransmission o blood borne diseases like HIV, Hepatitis B etc.
X Thereore, prophylactic transusion o FFP is not recommended.
However FFP may be useul in a Dengue patient with hepatic encephalopathy andhas active bleeding.
10.3 Steroids and I.V. immunoglobulin
Tere is no evidence to support the use o intravenous immunoglobulin and ster-oids in the management o dengue patients.
X Thereore, use o steroids (hydrocortisone, dexamethasone and methylpred-
nisolone) and/or immunoglobulin is not recommended.
10.4 Recombinant Factor VII
Tere is no evidence to support the use o recombinant actor VII in DHF patientswith bleeding due to prolonged shock, DIC or multi-organ ailure. Tereore, use
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o this as the treatment o bleeding in DHF due to such conditions is not rec-ommended. Recombinant actor VII is useul only in patients who have massivebleeding due to a specifc cause such as bleeding peptic ulcer or bleeding rom aspecifc place in the nose prior to surgical intervention. Tis helps to buy time orthe specifc surgical treatment like banding, cauterization etc. It should be used
only i defnite plans are there or surgical intervention as the arrest o bleedingwith recombinant actor VII is only temporary.10.5 Antibiotics
Tere is no evidence to support prophylactic use o antibiotics in DF or DHF pa-tients with low white blood cell count (WBC). It is also known that the low WBCis a very transient phenomenon. By the time the WBC is at its lowest, the marrowis already hyperplastic.
X Thereore, there is no place or the use o prophylactic antibiotics during the
rst 4-5 days o ever i Dengue is suspected, even in the presence o pleural
efusion or ascites.
10.6 Frusemide
Intravenous rusemide (1 mg/kg body weight) could be used in the ollowing cir-cumstances
y In uid overloaded patients who are haemodynamically stable
y In uid overloaded patients who are haemodynamically unstable in the mid-
way o a colloid inusion or a blood transusion
10.7 Tranexamic acid
Bleeding per vagina, either menstrual, intermenstrual or premenopausal, canbe excessive in DHF. Hence those who have such bleeding may be started on
tranexamic acid 1 gram eight hourly.
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11. Transerring a patient to another Institute
Facilities in some small hospitals may not be adequate to manage a patient in DHFwho has entered the critical phase. Furthermore, a patient in prolonged shockneeds to be managed in an intensive care unit. Hence, such patients may be trans-erred to an institution with adequate acilities.
Every such transer should be done aer obtaining advice rom the ConsultantPhysician who will be receiving the patient and aer resuscitating in accordancewith the advice.
Proper resuscitation beore transerring is especially important i the journey isgoing to take long. Adequate inormation regarding the patient should be providedin the transer orm and this should include daily uid balance, investigation re-
sults and treatment given.
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12. Discharge
Te ollowing criteria should be ulflled beore discharge rom hospital.
y
No ever or at least 24 hours without the usage o antipyretic drugsy At least two days have lapsed ater recovery rom shock
y Good general condition with improving appetite
y Normal HCT at baseline value or around 38 - 40 % when baseline value is not
known
y No distress rom pleural efusions or ascites
y When platelet count has risen above 50,000 /mm3
yNo other complications
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13. Laboratory Diagnosis
During the frst three days o the illness, PCR or dengue virus is usually positive.However, sensitivity and specifcity o this test vary rom laboratory to laboratory.NS-1 antigen is another test which can be done during the frst 5 days o ever.Sensitivity o this test varies and ranges rom 60-90%. Tough this is a simple anda rapid test it is not cost eective.
IgM antibody is likely to become positive aer fh to sixth day o the illness andconsidered as the best option or routine diagnosis as a positive result will make aprobable case o dengue to a highly suggestive case. IgM will persist in the blood orabout three months (in Primary Dengue) aer the acute illness and IgM responsemay not be detectable in 5-10% o Secondary Dengue. Te best way to confrm thediagnosis would be to detect a rising titre o IgG/HI antibody or seroconversion o
IgM or IgG in paired sera.
X Laboratory conrmation o Dengue Inection is generally not required or
clinical management o patients.
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14. Outbreak Response Plan or Hospitals
Tere have been increasing number o dengue outbreaks in many parts o thecountry. Tereore, having a hospital emergency response plan or dengue out-breaks is vital in early diagnosis and appropriate clinical management o cases tominimize complications and deaths.
Such a plan should include the following key elements:
y Outpatient care (with triage and resuscitation areas)
y Assess bed occupancy in each unit (with a view to identiying additional beds
during outbreaks)
y High-dependency care beds
y
Stang and surge capacity needsy Stock management o essential medicines and supplies
y Laboratory acilities
As the frst step, with the available resources, hospitals should develop andstrengthen their capacity to screen and triage suspected dengue patients at theout-patient departments.
Hospital sta including doctors, nurses and other categories should be trained and
assigned appropriate duties in case o an outbreak. It is essential to conduct regulartraining or medical sta based on the current guidelines on clinical managemento dengue ever and dengue haemorrhagic ever.
Following essential medicines, supplies, equipment and services should be avail-able in the hospitals providing inward care or patients with dengue haemorrhagicever :
Medicines:
y Paracetamol tablets
y Oral Rehydration Solution
y I.V. Fluids - Crystalloids : 0.9% saline, Colloids hyper-oncotic (plasma
expanders) : 10% Dextran 40 & 6% starch
y 25% or 50% Dextrose
y Parenteral Vitamin K
y Calcium Gluconate (10% solution)
y KCl (20 or 40 mmol concentrated solution)
y Sodium bicarbonate (8.4% solution)
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Supplies and equipment:
y Thermometers
y Sphygmomanometers
y I.V. access sets
y Oxygen delivery systems
y Micro centriuge (or bedside haematocrit assessment)
y Microscopes (or platelet count estimation)
y Glucometers (or blood sugar estimation)
y Observation charts
Laboratory support:
Laboratories should be equipped round the clock or basic tests such as ull-blood count (FBC), haematocrit, platelet count, white blood count (WBC), anddierential count.
More complicated patients will need blood sugar, liver unction tests, renal unc-tion tests, serum electrolytes (including serum calcium), blood gases, coagulationassays, chest x-rays & ultrasonography.
Blood Bank:
Fresh whole blood, packed red cells and other blood products should be availableon demand.
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Nameofthepatient:
BHT:
Dat
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Dur
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ate
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outfever
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