Penatalaksanan intensif pasien dengan Penyakit Tropik Berat di ICU

Dr .Dadik .Dadik Wahyu Wijaya SpAn

Departemen Anestesiologi & Reanimasi / Instalasi Pelayanan Intensif (ICU) FKFK-USU / RSUP H.Adam Malik - Medan

Indikasi Umum Pasien dirawat di ICU Berdasarkan Prioritas Berdasarkan Diagnosis Berdasarkan NilaiNilai-nilai Parameter Hasil Laboratorium

Penyakit Tropik Berat (yang sering di ICU :

Tetanus Berat (Severe Tetanus) DHF Grade IIIIII-IV (DSS) Malaria Berat (Severe Malaria)

TETANUS BERAT

Derajat Keparahan (Severity Grading) Philips Dakar Udwadia Gambaran Klinis Ablett Blect
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Philips Score
Waktu Masuk
Masa Inkubasi > 14 hari > 10 hari 5 10 hari 2 5 hari < 48 jam Imunisasi Lengkap < 10 tahun > 10 tahun Ibu diimunisasi Tidak diimunisasi Luka Infeksi Tidak diketahui Distal/perifer Proksimal Kepala Badan Komplikasi Tidak ada Ringan Tidak membahayakan Mengancam Nyawa (tidak langsung) Mengancam nyawa Total Skor <9 9 - 18 >18

Skor
1 2 3 4 5 0 2 4 8 10 1 2 3 4 5 1 2 4 8 10

Selama Perawatan
Spasme Hanya trismus Kaku seluruh badan Kejang terbatas Kejang seluruh badan Optistotonus Frekuensi Spasme 6 x dalam 12 jam Dengan rangsangan Terkadang spontan Spontan < 3x per 15 menit Spontan > 3x per 15 menit Suhu 36.7 - 37 C 37.1 37.7 C 37.8 38.2 C 38.3 38.8 C > 38.8 C Pernafasan Sedikit berubah Apnea saat kejang Kadang apnea setelah kejang Selalu apnea setelah kejang Perlu trakeostomi

Skor
1 2 3 4 5 1 2 3 4 5 1 2 4 8 10 0 2 4 8 10

Derajat Keparahan Ringan Sedang Berat

Ablett Classification of Severity

Grade I (mild) Mild trismus, general spasticity, no respiratory compromise, no spasms, no dysphagia Grade 2 (moderate) Moderate trismus, rigidity, short spasms, mild dysphagia, moderate respiratory involvement, ventilatory frequency > 30 Grade 3 (severe) Severe trismus, generalized rigidity, prolonged spasms, severe dysphagia, apnoeic spells, pulse > 120, ventilatory frequency > 40 Grade 4 (very severe) Grade 3 with severe autonomic instability
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Derajat Keparahan hendaknya tidak dipakai sebagai pedoman Kaku Kaku untuk indikasi rawat ICU Indikasi Rawat ICU bilamana caracara-cara konvensional yang dilakukan di ruang perawatan tidak berhasil mengatasi kejang /spasme atau pasien mengalami gangguan pernafasan akibat kejang atau aspirasi, aspirasi , atau telah terjadi gagal nafas atau gangguan sistem lain yang memerlukan terapi supportif. supportif.
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Clinical diagnosis of tetanus

Secure Airway
Tracheostomy

Benzodiazepines2 Midazolam Diazepam Antitoxin2 HIG im/it Equine antitoxin im

Manage autonomic dysfunction

Magnesium
2 2

Antibiotics2 Metronidazole

Inotropes

Benzodiazepines Bupivacaine Morphine

2 2 2

Consider DVT Prophylaxis1 Control Muscle Spasms

Benzodiazepines2 NDNMBAs1 Magnesium2 Dantrolene1 Baclofen2

Clonidine

Full primary course of immunisation1

Flow diagram showing the management of tetanus. 1limited evidence; 2some evidence; 3good evidence.
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Therapeutic Management
Immunization Wound debridement Antibiotics Control muscle spasm Control Autonomic Disturbance Other supportive therapy
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MANAGEMENT
1. Neutralize toxin outside of CNS - Human Tetanus Immune Globulin HTIG) HTIG ) 150 units/kg IM or 5,0005,00010,000 units IV - ATS 500 UI/kgBB intramuscular.

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MANAGEMENT
2.

Prevent further toxin release - Early surgical debridement of

wounds - Antibiotics : Metronidazole 500mg 8 hourly and Penicillin G 1 MU 66-8 hourly. Heavily contaminated wound may need additional antibiotics.
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MANAGEMENT
3. Minimize the effects of toxin already exists in CNS - Control rigidity and spasm - Respiratory support as necessary - Control of autonomic dysfunction.

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Drug used to control spasm and autonomic disturbance

Benzodiazepine Morphine Muscle relaxant: vecuronium vecuronium, , rocuronium rocuronium, , pancuronium Magnesium sulfate Dantrolen Baclofen Bupivacain, Bupivacain , atropine,
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Benzodiazepine
Common used as anticonvulsant in tetanus. Has sedative effect Dose of Diazepam vary 100100-400 mg/24 h max until 2400mg/24 h Preservative used can cause acidosis in large dose No/little effect on autonomic disturbance
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Magnesium Sulfate
- Pre synaptic neuromuscular blocker - Blocks catecholamine release from nerve and

adrenal medulla - Reduce receptor responsiveness to release catecholamines - It antagonizes calcium in myocardium and at the neuromuscular junction - Inhibits parathyroid hormone release

anticonvulsant-vasodilator
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Dose
Adult : a loading dose of 5 gram over 20 minutes IV followed by 1g hourly increasing to 2.5 gram hourly when necessary. Titrate to symptoms Pediatrics : 100mg /kg/24 hours, can be increased when necessary. Titrate to symptoms
Sometimes MgSO4 is inadequate to be used alone, combination with benzodiazepine is also mandatory
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Monitoring of possible side effects

- Patellar reflex Diminished at the level of Magnesium >4 mmol mmol/L /L - Respiratory depression because of muscle paralysis (>Mg 6 mmol/L) mmol/L) - Bradyarrhythmia Bradyarrhythmia, , hypotension - Urine output Low output causes drug accumulation - Blood Calcium level, blood Magnesium level should be checked regularly - Overdose may cause sedation and anesthesia.

Day 4

Day 6

Magnesium can be a prospective alternative for treatment of tetanus, especially when there are mass casualties since it reduces the need for mechanical ventilation, however, meticulous ICU monitoring is needed with ready for use ventilator.

Gempa Yogyakarta

Others Drugs & Regiment

Obat pelemas otot (muscle relaxant) intermittent bila diperlukan. diperlukan. Baclofen (beta [4[4-chlorophenyl] gamma amino butyric acid) sebagai P-GABA receptor agonist, menghambat pelepasan asetilkolin presinaps diotak, diotak, diberikan intrathekal Propofol (1,6 (1,6-diisopropyl phenol) dapat dipakai sebagai sedasi, sedasi, dengan dosis tritrasi. tritrasi .
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Others Drugs & Regiment

Penghambat beta :
Propanolol,Labetolol, Propanolol,Labetolol , Esmolol

Agonist alfaalfa-2 : Clonidine Dexmedetomidine Opioid kombinasi dengan sedative :

Morphine + midazolam atau diazepam

Sodium valproate ACE Inhibitor

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MANAGEMENT
Terapi supportif lainnya
Terapi fisik (fisioterapi) karena pasien imobilisasi cukup lama. Ventilasi mekanik Metabolik : Nutrisi enteral , ditambah parenteral bila perlu. Penggunaan inotropik dan atau vasopresor Antikoagulan
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3 major complications cause death

Ventilatory restriction leading to respiratory complication and sepsis Autonomic disturbance Stress ulcer/gastric bleeding

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DHF GR IIIIII-IV (DSS)

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DF I

DHF (Grades) II III IV

Febrile Phase (3-7 days)

Afebrile Phase (Critical Stage)

Convalescent Phase RECOVERY If Appropriate Treatment not provided, there is a high rist death

Grading the Severity of Dengue Infection

DF/DHF DF Grade* Symptoms Fever with two or more of the following signs : headache, retro orbital pain, myalgia, arthalgia Laboratory Leukopenia, Occasionally, Thrombocytopenia, may be present, no evidence of plasma loss Thrombocytopenia, < 100,000, Hct rise 20 % Thrombocytopenia, < 100,000, Hct rise 20 % Thrombocytopenia, < 100,000, Hct rise 20 % Thrombocytopenia, < 100,000, Hct rise 20 %

DHF

Above signs plus positive Tourniquet test Above signs plus spontaneous bleeding Above signs plus circulatory failure (weak pulse, hypotension, restlessness) Profound shock with undetectable blood presure and pulse

DHF

II

DHF

III

DHF

IV

* DHF Grade III and IV are also called as Dengue Shock Syndrome (DSS)

Clinical Manifestation DSS

Increase of Vascular permeability : Haemoconcentration, Haemoconcentration , Hypoalbuminemi, Hypoalbuminemi, , Shock, Pleural Hypoproteinemia, Hypoproteinemia effusion Thrombopathy Hemorrhage Coagulopathy
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PENATALAKSANAAN
Afebrile phase
Duration two days after febrile stage

Manifestations
In addition to the manifestations of DHF Grade II : Circulatory failurse manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or Hypotension with the presence of cold clammy skin and restlessness Capillary relief time more than two seconds

Management
Check haematocrits/platelet
Initiate IV Therapy (5% D/NSS) 10 ml/kg/h Check Haematocrit , vital signs, urine output every hour. If patient improves IV fluids should be reduced every hour from 10 to 6 and from 6 to 3 ml/kg/h which can be maintained up to 24 to 48 hours. If patients has already received one hour treatment of 20 ml/kg/hr of IV fluids and vital signs are not stable check haematocrit again and If haematocrit is increasing change IV fluid to colloidal solution preferably Dextran or plasma at 10 ml/kg/h every hr. If haematocrit is increasing from initial value give fresh whole blood transfusion, 10 ml/kg/h and continue fluid therapy at 10 ml/kg/h and reducing it stepwise bring down the volume to 3 ml/kg/h and maintain it up to 24 48 hours. Initial IV therapy (5% D/NSS) 20 ml/kg as a bolus one or two times Oxygen therapy should be given to all patients. In case of continued shock colloidal fluids (Dextran or Plasma) should be given at 10 20 ml/kg/hr.

Profound shock with undetectable pulse and blood pressure.

Afebrile phase

Manifestation
Profound shock with undetectable Pulse and blood pressure

Management
- If shock still persists and the haemotocrit level continues declining give fresh whole blood 10 ml/kg as a bolus - Vital signs should be monitored every 30 60 minutes - In case of severe bleeding gives fresh whole blood 20 ml/kg as a bolus - Give platelet rich plasma transfusion exceptionally when platelet counts are below 5.000 10.000 / mm3 - After blood transfusioncontinues fluid therapy at 10 ml/kg/h and reduce it stepwise to bring it down to 3 ml/kg/h and maintain in for 24 48 hrs

Con Phase
Duration 2 3 days After recovery from critical/shock stage

Manifestation
- 6 12 hours after critical/shock stage some symptoms of respiratory distress (pleural effusion or arcites) - 2-3 days after critical stage , strong pulse, normal blood pressure. - Improved general condition/return of appetite. - Good urine output - Stable haematocrit - Pletelet count > 50.000 per mm3 - Patient could bedischarged from hospital 2 3 days after critical stage - Bradycardia/arrhytmia - Asthenia and depression (few weeks) in adult

Management
- Rest for 1 2 days - Normal diet - No need for medication

Fluid Therapy in DSS

The policy of initial fluid therapy in DSS according to the Department of Health and WHO until 2003 : Crystalloid (Lactate Ringer), followed with colloid (Dextran (Dextran) ) if not responded

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Department of Health Indonesian Intensive Care Association Indonesian Anesthesiology Ass Indonesian Paed. Paed. Ass (2004)
Review on the management of DHF Change the protocol Include colloid MMWMMW-6% HES as alternative as initial fluid resuscitation in DSS

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Volume Replacement Therapy

Crystalloids Colloids

Lactated Ringer's Normal Saline

Albumin PPL

Gelatin solutions

Dextran solutions

HES solutions
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Crystalloid (RL, RA, NaCL) NaCL)

Distributed to the interstitial space Very short period in the intravascular space Need more fluid to maintain intravascular volume risk for interstitial edema / pulmonary edema

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Colloid
HES: ( MW 100.000100.000-300.000 kD ): Sealing effect +, good intravascular volume effect, longer duration in the intravascular space, DO2, VO2 Dextran : LMW colloid (40.000(40.000-70.000 kD kD) ) with good preservation volume effect, no sealing effect, effect, increase anaphylactic reaction
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Hydroxyethyl Starch (HES)

- Effective and safe plasma substitute
- HES broad range of MW, from very small until several hundred thousand Dalton

- Classification of HES (by in vitro) according to MW: - HIGH MOLECULAR WEIGHT (HMW) 450 K Da
- MEDIUM MOLECULAR WEIGHT (MMW) 200 K Da - LOW MOLECULAR WEIGHT (LMW) 70 K Da

Sealing effect : HES with 100 100300.000 D MW

Effect of HES on Blood Coagulation

HMWHMW -HES more effect on blood coagulation

(vWF, vWF, factor VIII) LMW (HES 70/0.5/4)/MMW(HES 70/0.5/4)/MMW(HES 200/0.5/6) 200/0.5/6) not affect on blood coagulation Possible dilutional coagulation effect : PT, aPTT (significant prolongation after HMWHMW-HES 480) did

Fluid Resuscitation in DSS

Primary importance in the management of hypoperfusion state Goal of therapy Tissue DO2 Blood Pressure VO2 Reversing Lactic Acidosis
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Colloid MMW

Study on DSS using colloid (HES ) as initial fluid resuscitation

Different RESULT Different method of study
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Tatty E. Setiati (2000) Herminia L. Cifra (2001) (2001 )H

RL group Duration of shock

( Hour)

Colloid group
(HAES Steril 6%)

7.9+/- 2.6

2.3 +/- 2

Ventilators days Pleural effusion

ALI /PaO2/FiO2=200-250

8 +/- 1.1 30
M2/Mod7/S21

4.0 +/- 0.71 _ 1 2

4 6

ARDS
PaO2/FiO2 < 200

Conclusion
Evidenced showed that endothelial dysfunction lead to vascular leakage and hemostatic disturbances occurred in DSS MMW which has a sealing effect could minimizing vascular leakage, good preservation volume effect, and lowering mortality MMW HES can be used as alternative for initial fluid resuscitation in DSSS DSSS

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What not to do in DSS

Do not give Aspirin or Ibuprofen for treatment of fever. Avoid giving intravenous therapy before there is evidence of haemorrhage and bleeding. Avoid giving blood transfusion unless indicated, reduction in haematocrit or severe bleeding. Avoid giving steroids. They do not show any benefit. Do not use antibiotics Do not change the speed of fluid rapidly, i.e. avoid rapidly increasing or rapidly slowing the speed of fluids. Insertion of nasogastric tube to determine concealed bleeding or to stop bleeding (by cold lavage) is not recommended since it is hazardous.
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Signs of Recovery
Stable pulse, blood pressure and breathing rate Normal temperature No evidence of external or internal bleeding Return of appetite No vomiting Good urinary output Stable haematocrit Convalescent confluent petechiae rash
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SEVERE MALARIA

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What is severe malaria?

Severe malaria is the serious or life-threatening form of falciparum malaria which needs active appropriate patient management. According to WHO criteria in 1990, severe malaria patients have asexual forms of Plasmodium falciparum on a blood film and may have any one or more of the following manifestations and complications :
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1. Cerebral malaria (unrousable coma not attributable to any other cause)

2.

Severe normocytic anemia (haematocrit <15% or hemoglobin <5 g/dl)

3. Acute renal failure (urine output <400 ml/24 hours in adults or 12 ml/kg/24 hours in children, failing to improve after redydration and serum creatinine >265 mmol/l (3 mg/dl)) 4. Pulmonary edema or adult respiratory distress syndrome (ARDS)
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5. Hypoglyceamia (whole blood glucose <2.2 mmol or l40 mg/dl) 6. Circulatory collapse, shock: hypotension (systolic blood pressure <50mmHg in children aged 1-5 years or <70 mmHg in adults), with cold clammy skin or core-skin temperature difference >10 C) 7. Spontaneous bleeding/disseminated intravascular coagulation (DIC) 8. Repeated generalized convulsions 9. Acidaemia (arterial pH <7.25) or acidosis (plasma bicarbonate <15 mmol/l) 10. Macroscopic haemoglobinuria 11. Post-mortem confirmation of diagnosis
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WHO MULTICENTER STUDY ON SEVERE MALARIA IN UNDER FIVES IN 10 AFRICAN COUNTRIES (1230 CASES, 1999 2000) PREVALENCE OF SIGNS AND SYMPTOMS

SIGNS AND SYMPOMS SEVERE ANEMIA PROSTRATION CONVULSIONS CEREBRAL MALARIA HYPOGLYCEMIA HYPOGLOBINURIA JAUNDICE RESPIRATORY DISTRESS DISSEMINATED INTRAVASCULAR COAGULATION

NUMBER 666 371 279 218 162 41 21 12 1

% 54.1 30.2 22.7 17.7 13.2 3.3 1.7 1.0 0.08

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Different clinical manifestation between adults and children with severe malaria
Adult
Cough Convulsions Uncommon early symptom Indicate cerebral involvement

Children
Common early symptom May indicate cerebral involvement or hypoglycemia, but may be non specific consequence of fever

Duration of symptoms before features of severe disease develop Jaundice Time from start of treatment to resolution of coma in cerebral malaria Hypoglycemia

Commonly several days

Usually 1 2 days only

Common Usually quinine 2 4 days

Uncommon Usually 1 2 days

Relatively uncommon Usually quinine-induced (especially in pregnancy) Common Common Uncommon

Common

Pulmonary edema Renal failure Neurological sequelae after cerebral malaria

Rare Rare Occur in about 10% of cases

Management
Parenteral antimalarials. IV fluid administration. Vital signs monitoring every 4 hours. Blood check up for malaria parasite every day until disappearance of parasitemia. Monitoring clinical signs and symptoms of severe malaria that may occur later. Record conscious level every 4 hours and urine output every 8 hours.
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Antimalarial drug doses in severe malaria

Hospital ICU Chloroquine-resistant P falcipanum Quinine Quinine dihydrochloride 7 mg salt/kg infused over 30 min followed by Immediately 10 mg/kg Over 4 h: or 20 mg salt/kg Infused over 4 h Maintenance dose: 10 mg Salt/kg infused over 2-8 h At 8 h intervals Arteminisim derivative : a) Artemether 3.2 mg/kg Stat By im injection Followed by 1.6 mg/kg Daily a) Artesunate 2.4 mg/kg stat By iv injection followed by 1.2 mg/kg daily Chloroquine sensitive P falcipanum Chloroquine Chloroquine 10 mg base/kg Infused iv at constant rate over 8 hr followed by 15 mg base/kg over 24 hr Health Clinic : No Intravenous Infusion Possible Quinine dihydrochloride 20 mg salt/kg diluted 1 : 2 with sterile water given by split injection into both anterior thighs. Maintenance dose : 10 mg/kg 8 hourly Rural health clinic : No injection facilities Artesunate rectocap : 10 mg/kg daily Artemisinin suppository 20 mg/kg at 0 and 4 h Then daily

As for Hospital ICU : Artesunate can also be Given by im injection

Chloroquine 3.5 mg Base kg 6-hourly or 2.5 mg base/kg 4 hourly by im or sc injection. Total dose 25 mg base/kg

Chloroquine 10 mg/kg daily Or nasogastric chloroquine as for oral regimen

Poor prognostic features in severe malaria

Clinical findings
Deep Coma Repeated convulsions Respiratory distress (rapid, deep, laboured, stertorous, breathing often with intercostals recession) Significant bleeding

Laboratory findings
Biochemistry Hypoglycemia Hyperlactatemia Acidosis Serum creatitine Total bilirubin Liver enzymes < 2.2 mmol/l > 5 mmol/l arterial pH<7.3 venous plasma HCO3 < 15 mmol/l >265 mol/l > 50 mol/l SGOT (AST) x 3 upper limit of normal SGPT (ALT) x 3 upper limit of normal 5 Nucleotidase CPK Myoglobin > 600 mol/l

Muscle enzymes Urate Hematology Leucocytosis Severe anemia Coagulopathy

>12.999/l PCV < 15 % Platelet < 50.000/l PT prolonged > 3 s Prolonged PPT Fibrinogen <200 mg/dl

Parasitology Hyperparasitemia

> 100.000/l - increased mortality > 500.00/l - high mortality >20% of parasites are pigment containing trophozoites and schizonts >5% of neutrophils contain visible malaria pigment

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