Management

Severe Malaria
and complications

Paul.N. Harijanto
MANAGEMENT SEVERE MALARIA
SUSPECTED CASE

 EARLY IDENTIFICATION & DIAGNOSIS

 MANAGEMENT & DETECTION VITAL ORGAN

FAILURE :
 Hemodynamic changes ( shock )
 Causes of Decresing Concious level ( hypoglycaemia )
 Respiratory failure ( breathless, rate > 30x/ minute )

 SPECIFIC TREATMENT
 ANTI MALARIAL DRUGS
 Early identification & Diagnosis
 Failed to take a proper history ( travel history,
location of living )
 Availablity microscopic examinations/ RDT

 Misleading diagnosis Malaria : ( Dengue,

Thyphoid, URTI )
 Misleading diagnosis complications :
 Coma : sepsis, meningitis, stroke
 Jaundice : Hepatitis, cholecystitis
 Renal failure : dehydration, acute gastroenteritis,
Intoksication
 INITIAL ASSESMENT
 Asses Airway, Breathing, Circulation
 Weigh BW for calculate dose artesunate
 Insert i.v. line (Solution NaCl 0.9%, preferable)
 Clinical Exam : Vital sign, GCS, jaundice, hepato-
splenomegali, lungs
 Measurement intake-output balance

 Lab : Bl. Sugar, Hematology, ureum, creatinine, serum

bilirubin, SGOT/SGPT, Sodium, Potassium, Bl. Gas,
lactate, Malaria smear
 C-X-Ray & ECG
 Early assesment/ warning sign :

 Development/ worsening of coma

 Convulsion

 Respiratory depression/ arrest

 Edema paru/ respiratory insufficiency

 Hemodinamiccally unstable

 Sepsis

 Acute Kidney Injury

 General danger signs suggesting severe febrile illness
as criteria for referral from peripheral health facilities

IMAI for adolescent & adults in areas of malaria transmission

 Fever or history of fever in the past 24 h plus one or
more of the following danger signs:
 Very weak or unable to stand
 Convulsions
 Lethargy
 Unconsciousness
 Stiff neck
 Respiratory distress
 Severe abdominal pain

IMAI : Integrated Management of Adolescent and Adult Illness

 General danger signs suggesting severe febrile
illness as criteria for referral from peripheral
health facilities
IMCI for children 2–59 months in areas of malaria transmission
 Fever or history of fever in the past 24 h OR palmar pallor plus one or more of
the following danger signs:

 Unable to drink or breastfeed

 Vomiting everything

 Multiple convulsions

 Lethargy

 Unconsciousness

 Stiff neck

 Chest indrawing or stridor

IMCI : Integrated Management of Childhood Illness

 SEVERE MALARIA

 Required parenteral or suppossitoria treatment

 Decreased parasitemia rapidly
 Less side effect
 LOADING Quinine vs Artemisinin ( ARTM , ARTS )
 ARTM trend to have low mortality but coma recovery
prolong, more convulsion
 ARTS Better than Quinine ( SEQUAMAT & AQUAMAT )
 ARTEMISININ

 Highly effective Anti-malarial drugs

 Potent, rapid, works all staging & spesies, less

toxic, no evidence of resistance
 Effective for severe malaria : intravenous,
intra muscular, suppossitoria
ANTI MALARIAL THERAPY FOR S.M
 Artesunate/ ARTS ( i.v./ i.m / supp )
 Artemether / ARTM (i.m.)
 Arte-ether (i.m )
 Artemisinin ( supp )
 Dihydro-artemisinin ( supp )
 Artelinate ( i.v)

 QUININE

 QUINIDINE
 RECOMMENDED DOSES OF ANTI MALARIAL DRUGS FOR
TREATMENT OF SEVERE MALARIA

DRUGS Dosis SIDE EFFECTS

ARTESUNATE i.v. 2,4 mg/kg BB pada jam 0, dan jam

12, kemudian dilanjutkan jam 24,
48 dst sampai 7 hari. Dosis total 17
– 18 mg/ 7 hari ( 1 Amp= 60 mg)

3.2 mg/kg im pada hari I , dilanjutkan

Artemeter 1.6 mg/kg/ hari. TIDAK iv (1 amp =
Neurotoxicity in
80 mg)
animal not human

Artemisinin Suppositories, 10 mg/kg at 0 & 4 hr

followed by 7 mg/kg at 24,36,48 &
60 hrs.

WHO 2006 : AS is the recommended FIRST CHOICE in area

low transmission
 Dosis ARTEMISININ PADA MALARIA
BERAT

0 JAM 12.J 24.J 48.J 72.J Max 7 hari

2.4 2.4 2.4 2.4 2.4

Mg/ Mg/ Mg/ Mg/ Mg/
KgBB KgBB KgBB KgBB KgBB

ARTESUNATE I.V/ I.M

• ARTEMETER , hanya I.M , 3,2 mg/hr1, lanjut dosis

• 1,6 mg/kg BB hari berikutnya
 ARTESUNATE
I.V / I.M

ARTEMETHER I.M
1 Amp = 80mg
1 Fl = 60 mg
Pre-Treatment 12 hours after Artesunate

24 hours after Artesunate

MANAGEMENT SEVERE MALARIA IN PREGNANCY
 RECOMMENDED DOSES OF ANTI
MALARIAL DRUGS FOR TREATMENT OF
SEVERE/CEREBRAL MALARIA

DRUGS SIDE EFFECTS

Quinine 20 mg of dihydrochloride salt/kg by
iv infusion over 4 hr, then after
loading, followed by 10 mg/kg
over 4 hr every 8 hr. Patients
should not received quinine or
mefloquine within last 24 hr
Alternatively, 7 mg of salt/kg can
be infused over a period of 30
min, followed by 10 mg salt/kg
over a period of 4 hr, or
Hypoglycemia,
chinchonism, tinnitus,
hearing impairment,
nausea, dysphoria,
vomiting, prolonged QT
interval, dysrhythmias,
hypotension

10 mg of salt/kg (500 mg for adult)

by i.v infusion over 8 hr
continously 3 x a day
 TREATMENT OF PARENTERAL QUININE- HCL

Loading
SETELAH KESADARAN MEMBAIK/DAPAT MINUM :
20 mg/kgBB IV infus/100-500 ml/4 jam GANTI PER-ORAL 10 MG/KGBB/8 JAM
Berat badan …. Kg SAMPAI HARI KE-7

Tak pakai Kina/Mefloquin 24 jam sebelumnya APABILA SETELAH 48 JAM

Tidak lanjut usia atau QT/QTc int. panjang KEADAAN TIDAK MEMBAIK :
GCS TETAP/MEMBURUK
BILIRUBIN / KREATININ NAIK
URIN KURANG / TAK ADA
Standard
10 mg/kgBB IV

DOSIS DITURUNKAN 30-50%
infus/200 ml/4 jam

10 mg/kgBB
IV infus 200 ml/4 jam 10 mg/kgBB
Infus kosong 4 jam IV infus 200 ml/4 jam
diulang tiap 8 jam
(tanpa kina)

Infus kosong 4 jam

(tanpa kina)

0 4 8 12 16 20 24
19/07/2019 Dr Hardianto Setiawan
WAKTU (JAM)
 TREATMENT OF PARENTERAL QUININE- HCL

SETELAH KESADARAN MEMBAIK/DAPAT MINUM :

GANTI PER-ORAL 10 MG/KGBB/8 JAM
SAMPAI HARI KE-7

APABILA SETELAH 48 JAM

KEADAAN TIDAK MEMBAIK :
GCS TETAP/MEMBURUK
BILIRUBIN / KREATININ NAIK
URIN KURANG / TAK ADA

DOSIS DITURUNKAN 30-50%

500 mg Kina HCl (1 amp) 500 mg Kina HCl (1 amp) 500 mg Kina HCl (1 amp)
dalam 500 cc Dextrose 5% dalam 500 cc Dextrose 5% dalam 500 cc Dextrose 5%

0 4 12 16 20 24
19/07/2019 Dr Hardianto Setiawan
WAKTU (JAM)
 Piggy
Dextrose 5% Cairan Back
Maintenance

Kina

Microdrips
100-200 cc

CARA PEMBERIAN

KINA PADA
MALARIA BERAT
 Penyesuaian dosis pada gangguan Fungsi Organ

 ARTESUNATE : Tidak perlu penyesuaian dosis obat

derivat artemisinin pada gangguan fungsi hati dan
atau ginjal
 Kina :Dosis kina parenteral diturunkan 1/3 setelah 48
jam pemberian pada :
 Gagal ginjal akut
 Gangguan fungsi hati
 Tidak ada perbaikan klinis setelah 48 jam
 Bila pasien sudah hemodialisis tidak perlu
pengurangan dosis kina
 Pengobatan lanjutan
 Setelah pasien sadar/KU membaik, tx. Awal parenteral
dapat diubah dgn. Tx. Oral, paling kurang parenteral
diberikan 3 x pemberian ( 24 jam )
 Diteruskan dengan :

 ACT dosis lengkap (selama 3 hari): AL , AS + AQ

 Artesunate/artemether tab. (total 7 hari ) + doksisiklin 3-

5 Kg BB 1 kali sehari selama 7 hari
 Kina tab.(total 7 hari) + doksisiklin 7 hari

 Bagi bumil, anak-anak : doksisiklin diganti dengan

klindamisin 10 mg/Kg BB 2 kali sehari
 Pengobatan Bumil Malaria Berat
 Trimester 2 -3 , durante/ post partum :
Artesunate i.v 2,4 mg/kg BB jam 0, 12, 24, 48
dst, bila sadar/ bisa minum obat ganti oral
sampai 5 – 7 hari. Bila oral artesunate 2
mg/kg BB diberikan sampai hari ke-7 (ars +
clindamycin)
 Trimester 1 : Kina HCl perinfus, 20 mg/kg BB
dosis awal dan 10 mg/kg BB selanjutnya
MANAGEMENT SEVERE MALARIA IN PREGNANCY
 Pengobatan pre-referal

 Dianjurkan sebelum merujuk setidaknya dosis

pertama obat antimalaria parenteral sudah diberikan.
 Obat yang dipilih :

 Artemether i.m. atau Artesunate i.m.

 Artesunate atau artemisinin supositoria

 Kina i.m.

 Kina i.v. (didampingi petugas medis ) ??

GENERAL SUPPORTIVE MEASURES
 Patients should be treated in an ICU

 In endemic areas treatment should be commenced as

early as possible, sometimes before positive
parasitology
 Patients should be weighed so that dose of anti malarial
can be calculated
 IV fluids should be given to maintain fluid balance and
caloric requirements. A central line and monitoring of
central venous pressure may be necessary, especially in
elderly. All intake should be recorded carefully
 Airway, Oxygen requirement

 Treat hyperpyrexia
GENERAL SUPPORTIVE MEASURES
 Urinary catheterization should be used to monitor output

 Patients should be observed for vomiting. To ensure patient’s

safety, cot-sides may be required
 Regular re-positioning of patient is necessary to prevent
development of pressure sores
 Nasogastric tube should be avoided because of the risk of
aspiration
 MONITORING GCS & VITAL SIGN

 LAB : FBC, GLUCOSE, PAR.COUNT, CREATININE, UREUM, BLOOD GAS,

URINE S.G, SODIUM, POTASSIUM.

 PREVENT : SHOCK, SEPTICAEMIA, ACIDOSIS, ARDS, HYPOGLYCAEMIA,

ASPIRATION, BEDSORES.
 MANAGEMENT OF ORGAN
FAILURE
 ENCEPHALOPATHY/
CONVULSION
 ANTI – CONVULSAN
 RENAL FAILURE  DIALYSIS – EQUIPMENT
 ACIDOSIS  BL. GAS ANALYSER
 20% DEXTROSE
 HYPOGLYCAEMIA
 VIT –K,
 HYPERBILIRUBINAEMIA  VENTILATOR
 CIRCULATORYSUPPORT
 RESPIRATORY FAILURE
 ANTI-BIOTIC&SUPPORT
 HYPOTENSION  TRANSFUSSION
 SEPSIS
 Mx Coma & Seizures
 ABCD ( A=airway, B= breathing, C=circulation,
D=dehydration)
 Correct hypoxia, hypoglycaemia and metabolic
acidosis
 Not/ difficult breathing: insert Guedel airway  bag
& mask ventilation
 Insert a nasogastric tube to empty the stomach

 Turning unconscious child every 2 h, attention to

pressure spots and oral and eye care
Management AKI :
- 30 % non-oliguric
- ( oliguric : < 0.5 cc/kg/ hr)
- Se creatinine > 2 mg/dl, should check daily

Manajemen :
Klinis dehidrasi : lakukan re-hidrasi Na Cl 0.9%,
10 ml/kg/jam ( 500ml/jam untuk 50 Kg)
Mencegah kelebihan cairan : respirasi rate,
askultasi paru, JVP, Oksimetri nadi,
CVP mesti di evaluasi setiap 200 ml cairan.
CVP : 0 – 5 cm
Diuretic in oliguric AKI
MANAGEMENT & DETECTION VITAL ORGAN FAILURE :

 Hemodynamic changes ( shock )

 Assesement Fluid requirement : individually
 Keep the fluid requirement : “ slightly dry “ , using
NaCl 0.9%, NOT LACTATE
 Prone developed Lung edema
 Giving bolus IV fluid either Colloid or Crystaloid is
CONTRA-INDICATED
 Clinical monitoring is important : development
breathless,JVP, respiration rate, rales in
auscultation, urine production
 PEDOMAN CAIRAN
 Kebutuhan cairan pada malaria berat harus diperhitungkan
individual/ berbeda pada masing2 kasus.
 Ada kecenderungan overload/ edema paru. “ Keep the patient
(slightly) dry “
 Pada anak sering terjadi dehydrasi karena kesulitan intake
maupun demam yang lama.
 Pemberian cairan secara bolus/ cepat, baik colloid maupun
kristaloid adalah kontra-indikasi.
 Pada AKI/ asidosis, gagal rehydrasi  Dialysis
 Pada anak dengan anemia  transfusi darah
 Perlu sering evaluasi JVP, perfusi jaringan, produksi urin,
ronki paru.
 - PEDOMAN PEMBERIAN CAIRAN -
 Pada dewasa dan anak :
 Malaria Falsiparum Berat : cairan yang direkomendasikan ialah NaCl
0.9% ; pemberian albumin tidak bermanfaat dan meningkatkan
mortalitas (FEAST study), transfusi bila Hb < 7 gr% (dewasa)
 DEWASA : Cairan awal NaCl 0.9% 3-5ml/kgBB/jam, selama 6 jam
pertama, lanjut 2-3 ml/kgBB/jam , evaluasi tiap 6 jam.
 ANAK : Cairan awal NaCl 0.9% 3-5ml/kgBB/jam, dalam 3-4jam
pertama, dilanjutkan 2-3 ml/kgBB/ jam dekstrose 5% atau bila
mungkin ( dipilih 0.45% NS/5% Dextrose)
 Monitoring elektrolit, gula darah dan koreksi seperlunya.
 Bila syok umumnya karena sepsis, beri anti-biotik
 Bila AKI/ oliguria, cairan 5 ml/kg BB iv bolus diikuti, bila tak ada urin,
dilakukan RRT ( dialysis)
 Management SHOCK
 Adults : systolic < 80 mmHg + impaired perfussion

 Children :
 Compensated : Clin impaired perfussion (2 or > of CRT >3s,
weak pulses, severe tachycardia & cool peripheries +
normal BP
 Decompensated : 1 or > above + sys <70 mmHg

 Mx : NOT Bolus, severe dehydration should corrected

slowly, optimum rate 5 ml/kg/hr.

 Acidosis & shock : Maintenence fluids

Maintenance fluids
 5% Dextrose , 3-4 ml/kg/hr until able to drink

 Hypoglycaemia : bolus 20% glucose, 2 ml/kg

over 10 min, or if unavailable, 50% 1 ml/kg
over 10 min

 Ideally, 0.45% NS-5% Dextrose, 3-5 ml/kg/hr

over 3-4 hr, the 5 % Dextrose 2-3 ml/kg/hr
until able to take oral.
Adult severe shock & hypotension

 Rapid infusion NS 0.9%, 20 ml/kg, perfusi

tercapai, STOP, bila tak tercapai :

 Norepinephrine ( nor-adrenaline) :
dopamine/ epinephrine, 250 mg/ 500ml NS,
dose tailoring.

 Bila sepsis : antibiotik adekuat

 - RESUME GUIDELINE FLUID REQUIREMENT
-
 Adults and Children > 14 years :
 Severe Falciparum :
 Adults & Children > 14 years : NaCl 0.9% 3-
5ml/kgBW/hour, first 6 hours, continued with 2-3
ml/kgBW/hour , evaluation every 6 hours
 Children < 14 years : NaCl 0.9% 3-5ml/kgBW/hour in
the first 3-4 hours, continued with 2-3 ml/kgBW/ hour,
Dextrose 5% in hypoglycaemia
 Monitoring electrolyte, blood glucose .
Mx. Hypoglycaemia :
• Chek in all impaired councious/ convulsion/ acidosis
• Common in children and pregnancy
• SM with jaundice or chronic liver disease
• Severe hyperparasitemia
• In the past assoc with Rx Quinine iv
Respiratory distress/ hypoxemia
Etiology : - Metabolic acidosis
- Pulmonary edema/ ARDS
- Pneumonia
- Severe anaemia
Investigations :
- Kussmaul Breath, rales diffuse
- Saturation O2
- FBC
- Chest X-ray
Rx : - Oxygenation  sat. o2 > 90 %
- Oxygen 4 – 6 L/min
CM-ARDS, RSUP 2000
Mechanical ventilation in ARDS
• Pressure support ventilation with positive end-
expiratory pressure (PEEP), avoidance of both
high tidal volumes (6 mg/kg ideal body weight)
and prolonged periods of high inspiratory
oxygen pressures.
• Permissive hypercapnia is not recommended
because this exacerbates the increased
intracranial pressure and brain swelling
• Rapid sequence intubation should be carried out
to prevent hypercapnia
Mechanical ventilation in ARDS
- continued -
 Good respiratory care is also important,
with intermediate ballooning and suction of
secretions, as well as appropriate
recruitment procedures.
 In refractory hypoxaemia, reversal of the
inspiration/ expiration ratio is indicated.
 Putting the patient in the prone position can
dramatically improve oxygenation
 MALARIA HEPATOPATHY
 Malaria Hepatopathy : to describe hepatocellular
dysfunction in cases of malaria. MH was diagnosed in pt
having:
at least > 3x serum amino transferase.
rise of serum total bilirubin along more than 3 mg/dL
absence exposure to hepatotoxic drugs & viral
hepatitus
clinical response to antimalarial drugs
• WHO 2015: Severe falciparum malaria with icterus:
presence of P.falciparum asexual parasitaemia, serum
bilirubin >3 mg/dL, parasIte count > 100 000/uL
Management liver dysfunction

 Management the complication

(Hypoglicemia>>)
 Malaria biliosa: injection vitamin K 10 mg/d IV
for 3 days
 Additional aspect of managemet (fluid
therapy, blood transfusion, concomitant use of
antibiotics, use of anticonvulsants)
 Hepatic encephalopathy : treat accordingly
Mx Bleeding disorders
 Thrombocytopenia is common in malaria, bleeding is
uncommon
 If bleeding occur, DIC should be suspected and related
bacterial sepsis
 Antibiotic treatment should always be given in children with SM
 Low-dose heparin, antithrombin or recombinant activated
Protein C therapy are no longer recommended for DIC, nor is
the use of fresh frozen plasma to correct laboratory clotting
abnormalities unless there is bleeding
 Platelets can be administered when the platelet counts are <
5000/mm3 regardless of bleeding or if there is significant
bleeding and counts are below 30 000/mm3 .
Blood transfussion in malaria
HAEMOGLOBINURIA/ Black water fever

 Continue full dose anti malarial

 Transfusion until Ht > 20%

 Re-hydrasi , adequate urine output

 Alkalinisation urine : 100-150 meq/l

Sodium bicarbonate in 5% Dextrose
 MANAGEMENT ACIDOSIS
Bila ph < 7.10, beri 1-2 meq/kg/hr ( 1 ampul 100
meq HCO3/ 50 kg, diberikan 1-2 jam)
Mx Sepsis in Malaria
Treated Secondary Bacterial Infection

 Adult ? ( personal view ..)

 Severe Malaria in adults with leucocyte > 12.000/ uL,
treat with AB, until general condition improved, no
bacterial infection STOP AB

 Choice AB :
 Broad-spectrum : Ceph. III/IV, Carbapenem
 Considering local AB guideline (Empheric Rx) or
culture results
 J. Penanganan terhadap infeksi sekunder/
sepsis
 WHO (2015), merekomendasikan pemberian antibiotik broad-spektrum
pada malaria berat pada anak sampai dipastikan tidak ada infeksi
bakterial.

 Setelah pengobatan anti-malarial, bila kondisinya memburuk dapat

diartikan adanya infeksi bakterial

 Bila pasien sudah negatif pemeriksaan malaria dan masih demam,

penyebabnya ialah infeksi bakterial seperti salmonella atau infeksi
saluran kemih

 Obat pilihan ialah Cephalosporin generasi III atau IV atau derivat

Carbapenem
 Precaution
 Hygiene precaution ( hand hygiene ,
aseptic procedure )

 Stress ulcer prophylactis : PPI/ H2-blockers

 DVT prophylactis : low molecular heparin,

anti-thrombotic stockings or elastic
bandages

 Mobilisation
 Spesific supportive treatments
 Inserted Guedel oropharyngeal airway  prevent
aspiration

 Intubated  mechanical ventilation

 Nasogastric tube : regular sucction. Non-intubated

adult, naso gastric tube after 60 hours from
admission

 Oral hygiene

 Urine catheters : measuring urine output

 Consciousness deterioration : CT scan/ MRI , to

exclude intracerebral bleeding/ raised ICP, brain
edema/ herniation
 PANDUAN & PERINGATAN

1. Malaria berat adalah kasus “ Kegawatan Kedaruratan “,

HARUS di-diagnosa dan ditangani secara cepat dan akurat
2. Perlu melihat sendiri pasien dan bila perlu slide malarianya.
3. Artesunate intra-vena adalah obat pilihan, artemeter i.m
sebagai alternatif, ACT per oral bila bisa minum oral, kina
injeksi adalah pilihan terakhir
4. Sebelum merujuk beri dosis awal artesunate/artemeter/
kina/ACT
5. Jangan memberikan tindakan/ obat bila tidak yakin
kebenarannya (Loading Cairan/ R/L, Steroid )
6. Lakukan Collaboration/ komunikasi-informasi tentang obat
dan tindakan yang harus dilakukan. (wap/ line/ sms )
 KEY SUCCEED FOR MANAGING
SEVERE MALARIA

 Accuracy diagnosis ( microscopic – biochemical )

 Effective Malaria drug ( to combat resistency )

 Ability to treat organ failure ( ICU & Medical

equipment )
 Good man power( nurses --- doctor )

 Good referral system

PAKATUAN WO PAKALAWIREN
Till we meet again !
Dr. Paul Harijanto, Sp.PD-KPTI, FINASIM
Lecturer in Sam Ratulangi Medical Faculty
DEPT. INTERNAL MEDICINE
Bethesda Hospital –TOMOHON
NORTH-Sulawesi, INDONESIA

Telp.: +62-431-351046(Bethesda)
+62-812-431-2869 (HP)
E-mail : paulharijanto@gmail.com