Management

Organ Failure in
Severe Malaria

Paul.N. Harijanto
Severe manifestations of Plasmodium falciparum malaria in adults and children

Prosnostic (+ -- +++) Frequency + -- +++

Children Adults Clinical Manifestation
Children Adults
+++ +++ Impaired consciousness +++ ++
+++ +++ Respiratory distress (acidotic) +++ ++
+ ++ Multiple convulsions +++ +
+ + Prostration + +
+++ +++ Shock + +
+++ +++ Pulmonary oedema +/- +
+++ ++ Abnormal bleeding +/- +
++ - Jaundice + +++
+ + Severe Anemia +++ +
+++ +++ Hypoglycaemia +++ ++
+++ +++ Acidosis +++ ++
+++ +++ Hyperlactaemia +++ ++
++ ++ Renal Impairment + +++
+/- ++ Hyperparasitemia ++ +
Bedsite Classifications SM in Children (<12 yrs )
 Group 1: (require parenteral Rx & Support.Tx )
1. Prostration ( inability to sit upright), 3 subsgroup :
 Prostrate but fully concious
 Prostrate with impaired conciousness not coma
 Coma
2. Respiratory distress ( acidotic breathing
 Mild – nasal flaring &/ or mild intercostal indrawing
 Severe – mark intercoctal indrawing or deep acidotic
3. Shock compensated/ decompensated

 Group 2 (able to take oral Rx, require supervised who risk develop to
group 1), these include :
1. Haemoglobin < 5 gr% or haematocrit < 15%
2. > = 2 convulsions in 24 hours
3. Haemoglobinuria
4. Jaundice
5. Parasitemia > 10%

 Group 3 : require parenteral Tx because of persistent vomiting, not in

group 1 or 2.
 Bedside clinical classification of severe malaria in adults
GROUP 1 . Required Parenteral Rx & Support Mx
 Adults at increased risk of dying Prostrated or obtunded
adults (inability to sit or to drink):
 Prostrate but fully conscious
 Prostrate with impaired consciousness, not in coma (GCS >
11)
 Confusion and agitation (GCS > 11)
 Coma (the inability to localise a painful stimulus) (GCS < 11)

 Respiratory distress (acidotic breathing)

 Mild – sustained nasal flaring and/or mild intercostal indrawing (recession)
 Severe – the presence of either marked indrawing (recession) of the bony
structure of the lower chest wall or deep (acidotic) breathing
 Shock (hypotension:systolic BP < 80 mmHg)
 Anuria

 Significant upper gastrointestinal haemorrhage

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

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 .
CASE
 Male.14 years old, admitted to hospital with fever a
week, chills & rigor, sweating , cough and vomiting 4
x. makan minum sedikit, unable to eat for 2 days.

On examination :
Consious, ill , no dehydration, BP 80/ 60 mmHg, 90/60
mmHg, Temperature 40 C, Resp 26 x/min, Nadi 100x/min
Heart : S1-2, normal. Lung : no ronchi.
Abdomen : normal, liver & spleen not palpable

 LABORATORY RESUTS :

 HematologY : Hb. 12.3 gr%, Leuco 5110/uL, Ht.

33.6%, Thrombocyte 24.000/uL, Diff neutro 70%, limf
23%, mono 3.6%, eos 2.5%, baso 0.2%
Diagnosis & Management ?
 He did a camping in Tombatu (
endemic area) then last 2 weeks

Malaria smear :
P. Falcip +++ ring form,
3000 par/200leuco ( 75000/ uL ), 12 par/ 1000 erythrocyte
After artesunate treatment :
1000 par/ 200 leuco, 6 par/ 1000 ery ( 12 hous )
45 par/ 200 leuco, 1 par/ 1000 ery ( 24 hours)
20 par/ 200 leuco, negatip/ 1000 ery ( 36 burs )
Negative smear ( 48 hours )
 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
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
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
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
KASUS
 Laki-laki, 27 thn, demam 5 hari, sakit kepala,
nafsu makan kurang, rasa lemah. Minum obat
darplex 3 hari tanpa tambahan Primakuin
 Kes: CM, Tensi: 100/80, Nadi: 84, temp: 38,
Resp: 20x, tidak anemis . Thorax: Jantung S1/S2
normal, murmur –, Paru: Rh-/-, wh-/-. Abd: Hepar
lien ttb, peristaltic normal, nyeri tekan abdomen -
. Extremitas: hangat,
 Lab: P vivax +
 RL guyur 1 kolf, dilanjutkan Dex 5% 20 tts/mnt
 Artsunat 2 vial IV 0-12-24-48
 Primakuin 1x1
 Ranitidine 2x1amp
 Pct drip 3x1gr

Apa pendapat sejawat tentang terapi diatas ?

 Hari ke-2

 Merasa sudah lebih baik. Mengeluh kalau

kencingnya merah kehitaman. Kesadaran
CM, pasien bisa sendiri datang ke ruang
perawat untuk bercerita dan makan
makanan kecil/sarapan
 Hari ke-3
 Keluhan agak sesak. CM
 T: 130/80, N: 84, RR: 28 x/menit
 Mata: tampak pucat, sklera, Ikterus
 Thorax: Jantung Normal, Paru vesikuler, rhonchi -, wheezing –
 Abdomen nyeri -, ; Hepar/lien tidak teraba
 Ext: hangat APA PENDAPAT ANDA ?

O2 2 L/mnt; Asering/Dex 5% 20 tts/mnt

Omeprasol x1 vial; Sistenol 3x1 ; Biocurliv 3x1
Ranitidine (stop); Parasetamol(stop)
Terapi lain lanjut. ( Artesunat dan Primakuin )
Dianjurkan pasang kateter, tetapi pasien menolak.
P/ DL,UL,GDS,Ureum/SC, SGOT/SGPT; Bil total/direk ; HBsAg
EKG dan USG abdomen
 hari ke-4
TS mengeluh masih rasa Sesak+ ; Demam – ; Mual +, muntah -,
Belum kencing

KOMENTAR ANDA ??

Kes CM , T: 160/100, RR: 28x/mnt, N: 96, t: 36,6 ; lain sama

Hasil lab : WBC : 25,680 ; HB: 5,3 ; PLT: 160000 ; Ureum: 225
; Creatinin: 12,5
SGOT: 259 ; SGPT :100 ; Bil Tot:9,37 ; BilDirek 5,48 ; As Urat:
13,7
EKG : N
USG Abd: hepatitis, PNC bilateral, Obstruksi Bilier tdk ada
APA DIAGNOSA & PENDAPAT ANDA ?
 Diagnosa & Tindakan

 Malaria tertiana Berat, dengan Black Water Fever,

 AKI dd Akut on CKD dengan Oliguria
 Anemia berat
 Susp Hepatitis Virus
 Hipertensi Stg 2

Resusitasi cairan, O2 3 - 5 L/menit

Ceftriaxon 1x2 gr ; Furosemid 1 amp iv ; Obat lain lanjut.
Diet ginjal ; Monitor ketat,
Pasang kateter dan persiapan dirujuk untuk segera mendapat HD
Ditawarkan HD pilihan Dok 2 dan Makasar.
 Hari ke-4

 Pasien mengeluh masih sesak. Kes CM ; T: 140/90 ; RR 28

 10 menit kemudian, pasien tiba-tiba mengeluh bertambah
sesak, Apnoe dan kejang ; TD 60/- ; Nadi tidak teraba
 RJP ; Resusitasi cairan dan O2 6 L/menit ; Inj. Epineprin 1
amp iv ; SA 1 amp; Sambil penanganan dilakukan, TS
didorong ke ICU
 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 )
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
 Etiology Hypoglycemia
 Parasites required carbo-hydrat for metabolism

 Impaired gluconeogenesis

 Quinine induced insulin formation

( hyperinsulinisme )
 Raised Tumor Necrosis factor (TNF-alfa)
 ACUTE KIDNEY INJURY (AKI)

 Malaria related Acute Kidney Injury (MAKI)

 Penurunan fungsi ginjal dalam 48 jam :

 Peningkatan serum kreatinin 0.3 mg/dL, atau
 Peningkatan serum kreatinn 50% dan nilai
dasar, atau
 Penurunan urin output 0.5 ml/kg/jam untuk 6
jam
 WHO : serum kreatinin > 3 mg/dL

 Sering pada malaria dewasa dan jarang pada anak

Purpura ( Subcutaneus bleeding in malaria
with thrombosit 2000/ mm3