Penatalaksanan Penatalaksanan intensif intensif pasien pasien dengan dengan
Penyakit Penyakit Tropik Tropik Berat Berat
di di ICU ICU Dr . Dr .Dadik Dadik Wahyu Wahyu Wijaya Wijaya SpAn SpAn Departemen Departemen Anestesiologi Anestesiologi & & Reanimasi Reanimasi / / Instalasi Instalasi Pelayanan Pelayanan Intensif Intensif (ICU) (ICU) FK FK--USU / RSUP USU / RSUP H.Adam H.Adam Malik Malik -- Medan Medan 1 1 Indikasi Indikasi Umum Umum Pasien Pasien dirawat dirawat di di ICU ICU Berdasarkan Berdasarkan Prioritas Prioritas Berdasarkan Berdasarkan Diagnosis Diagnosis Berdasarkan Berdasarkan Nilai Nilai--nilai nilai Parameter Parameter Hasil Hasil Laboratorium Laboratorium 2 2 Penyakit Penyakit Tropik Tropik Berat Berat (yang (yang sering sering di di ICU : ICU : Tetanus Tetanus Berat Berat (Severe Tetanus) (Severe Tetanus) Tetanus Tetanus Berat Berat (Severe Tetanus) (Severe Tetanus) DHF Grade III DHF Grade III--IV (DSS) IV (DSS) Malaria Malaria Berat Berat (Severe Malaria) (Severe Malaria) 3 3 TETANUS BERAT TETANUS BERAT TETANUS BERAT TETANUS BERAT 4 4 Derajat Derajat Keparahan Keparahan (Severity Grading (Severity Grading)) Philips Philips Dakar Dakar Dakar Dakar Udwadia Udwadia Gambaran Gambaran Klinis Klinis Ablett Ablett Blect Blect 5 5 Philips Score Philips Score Waktu Masuk Skor Selama Perawatan Skor Masa Inkubasi > 14 hari > 10 hari 5 10 hari 2 5 hari < 48 jam 1 2 3 4 5 Spasme Hanya trismus Kaku seluruh badan Kejang terbatas Kejang seluruh badan Optistotonus 1 2 3 4 5 Imunisasi Lengkap < 10 tahun > 10 tahun Ibu diimunisasi Tidak diimunisasi 0 2 4 8 10 Frekuensi Spasme 6 x dalam 12 jam Dengan rangsangan Terkadang spontan Spontan < 3x per 15 menit Spontan > 3x per 15 menit 1 2 3 4 5 Luka Infeksi Suhu Luka Infeksi Tidak diketahui Distal/perifer Proksimal Kepala Badan 1 2 3 4 5 Suhu 36.7 - 37 C 37.1 37.7 C 37.8 38.2 C 38.3 38.8 C > 38.8 C 1 2 4 8 10 Komplikasi Tidak ada Ringan Tidak membahayakan Mengancam Nyawa (tidak langsung) Mengancam nyawa 1 2 4 8 10 Pernafasan Sedikit berubah Apnea saat kejang Kadang apnea setelah kejang Selalu apnea setelah kejang Perlu trakeostomi 0 2 4 8 10 Total Skor Derajat Keparahan < 9 Ringan 9 - 18 Sedang >18 Berat 6 6 Grade I (mild) Mild trismus, general spasticity, no respiratory compromise, no spasms, no dysphagia Grade 2 (moderate) Ablett Classification of Severity 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 7 7 Derajat Derajat Keparahan Keparahan hendaknya hendaknya tidak tidak dipakai dipakai sebagai sebagai pedoman pedoman Kaku Kaku untuk untuk indikasi indikasi rawat rawat ICU ICU Indikasi Indikasi Rawat Rawat ICU ICU bilamana bilamana cara cara--cara cara konvensional konvensional yang yang dilakukan dilakukan di di ruang ruang konvensional konvensional yang yang dilakukan dilakukan di di ruang ruang perawatan perawatan tidak tidak berhasil berhasil mengatasi mengatasi kejang kejang //spasme spasme atau atau pasien pasien mengalami mengalami gangguan gangguan pernafasan pernafasan akibat akibat kejang kejang atau atau aspirasi aspirasi, , atau atau telah telah terjadi terjadi gagal gagal nafas nafas atau atau gangguan gangguan sistem sistem lain yang lain yang memerlukan memerlukan terapi terapi supportif supportif.. 8 8 Clinical diagnosis of tetanus Secure Airway Tracheostomy Benzodiazepines 2 Midazolam Diazepam Antitoxin 2 HIG im/it Equine antitoxin im Antibiotics 2 Metronidazole Manage autonomic dysfunction Flow diagram showing the management of tetanus. 1limited evidence; 2some evidence; 3good evidence. Magnesium 2 Inotropes 1 Benzodiazepines 2 Bupivacaine 2 Morphine 2 Clonidine 2 Consider DVT Prophylaxis 1 Control Muscle Spasms Benzodiazepines 2 Dantrolene 1 NDNMBAs 1 Baclofen 2 Magnesium 2 Full primary course of immunisation 1 9 9 Therapeutic Management Therapeutic Management Immunization Immunization Wound debridement Wound debridement Antibiotics Antibiotics Antibiotics Antibiotics Control muscle spasm Control muscle spasm Control Autonomic Disturbance Control Autonomic Disturbance Other supportive therapy Other supportive therapy 10 10 MANAGEMENT MANAGEMENT 1. 1. Neutralize toxin outside of CNS Neutralize toxin outside of CNS -- Human Tetanus Immune Globulin Human Tetanus Immune Globulin HTIG HTIG)) 150 units/kg IM or 5,000 150 units/kg IM or 5,000-- HTIG HTIG)) 150 units/kg IM or 5,000 150 units/kg IM or 5,000-- 10,000 units IV 10,000 units IV -- ATS ATS 500 UI/kgBB intramuscular. 500 UI/kgBB intramuscular. 11 11 22. . Prevent further toxin release Prevent further toxin release -- Early surgical debridement of Early surgical debridement of wounds wounds -- Antibiotics : Antibiotics : Metronidazole Metronidazole 500mg 500mg MANAGEMENT MANAGEMENT -- Antibiotics : Antibiotics : Metronidazole Metronidazole 500mg 500mg 8 hourly and Penicillin G 1 MU 6 8 hourly and Penicillin G 1 MU 6--88 hourly. hourly. Heavily contaminated wound may Heavily contaminated wound may need additional antibiotics. need additional antibiotics. 12 12 MANAGEMENT MANAGEMENT 3. 3. Minimize the effects of toxin already Minimize the effects of toxin already exists in CNS exists in CNS -- Control rigidity and spasm Control rigidity and spasm -- Control rigidity and spasm Control rigidity and spasm -- Respiratory support as necessary Respiratory support as necessary -- Control of autonomic dysfunction. Control of autonomic dysfunction. 13 13 Drug used to control spasm and Drug used to control spasm and autonomic disturbance autonomic disturbance Benzodiazepine Benzodiazepine Morphine Morphine Muscle relaxant: Muscle relaxant: vecuronium vecuronium, , rocuronium rocuronium, , Muscle relaxant: Muscle relaxant: vecuronium vecuronium, , rocuronium rocuronium, , pancuronium pancuronium Magnesium sulfate Magnesium sulfate Dantrolen Dantrolen Baclofen Baclofen Bupivacain Bupivacain, atropine, , atropine, 14 14 Benzodiazepine Benzodiazepine Common used as anticonvulsant in Common used as anticonvulsant in tetanus. tetanus. Has sedative effect Has sedative effect Dose of Diazepam vary 100 Dose of Diazepam vary 100--400 mg/24 h 400 mg/24 h Dose of Diazepam vary 100 Dose of Diazepam vary 100--400 mg/24 h 400 mg/24 h max until 2400mg/24 h max until 2400mg/24 h Preservative used can cause acidosis in Preservative used can cause acidosis in large dose large dose No/little effect on autonomic disturbance No/little effect on autonomic disturbance 15 15 Magnesium Sulfate Magnesium Sulfate -- Pre synaptic neuromuscular blocker Pre synaptic neuromuscular blocker -- Blocks catecholamine release from nerve and Blocks catecholamine release from nerve and adrenal medulla adrenal medulla -- Reduce receptor responsiveness to release Reduce receptor responsiveness to release catecholamines catecholamines -- It antagonizes calcium in myocardium and at It antagonizes calcium in myocardium and at the neuromuscular junction the neuromuscular junction -- Inhibits parathyroid hormone release Inhibits parathyroid hormone release anticonvulsant-vasodilator 16 16 Dose Dose Adult : a loading dose of 5 gram over 20 Adult : a loading dose of 5 gram over 20 minutes IV followed by 1g hourly minutes IV followed by 1g hourly increasing to 2.5 gram hourly when increasing to 2.5 gram hourly when necessary. Titrate to symptoms necessary. Titrate to symptoms necessary. Titrate to symptoms necessary. Titrate to symptoms Pediatrics : 100mg /kg/24 hours, can be Pediatrics : 100mg /kg/24 hours, can be increased when necessary. Titrate to increased when necessary. Titrate to symptoms symptoms Sometimes MgSO4 is inadequate to be used alone, combination with benzodiazepine is also mandatory 17 17 Monitoring of possible side effects Monitoring of possible side effects -- Patellar reflex Patellar reflex Diminished at the level of Magnesium >4 Diminished at the level of Magnesium >4 mmol mmol/L /L -- Respiratory depression because of muscle Respiratory depression because of muscle paralysis (>Mg 6 paralysis (>Mg 6 mmol mmol/L) /L) -- Bradyarrhythmia Bradyarrhythmia, hypotension , hypotension -- Bradyarrhythmia Bradyarrhythmia, hypotension , hypotension -- Urine output Urine output Low output causes drug accumulation Low output causes drug accumulation -- Blood Calcium level, blood Magnesium level Blood Calcium level, blood Magnesium level should be checked regularly should be checked regularly -- Overdose may cause sedation and anesthesia. 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 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 Others Drugs & Regiment Obat Obat pelemas pelemas otot otot (muscle relaxant) (muscle relaxant) intermittent intermittent bila bila diperlukan diperlukan. . Baclofen Baclofen (beta (beta [4 [4--chlorophenyl] gamma chlorophenyl] gamma amino butyric acid) amino butyric acid) sebagai sebagai PP--GABA GABA amino butyric acid) amino butyric acid) sebagai sebagai PP--GABA GABA receptor agonist, receptor agonist, menghambat menghambat pelepasan pelepasan asetilkolin asetilkolin presinaps presinaps diotak diotak, , diberikan diberikan intrathekal intrathekal Propofol Propofol (1,6 (1,6--diisopropyl phenol) diisopropyl phenol) dapat dapat dipakai dipakai sebagai sebagai sedasi sedasi, , dengan dengan dosis dosis tritrasi tritrasi. . 22 22 Others Drugs & Regiment Others Drugs & Regiment Penghambat Penghambat beta : beta : Propanolol,Labetolol Propanolol,Labetolol, , Esmolol Esmolol Agonist alfa Agonist alfa--2 : 2 : Clonidine Clonidine Dexmedetomidine Dexmedetomidine Dexmedetomidine Dexmedetomidine Opioid Opioid kombinasi kombinasi dengan dengan sedative : sedative : Morphine + Morphine + midazolam midazolam atau atau diazepam diazepam Sodium Sodium valproate valproate ACE Inhibitor ACE Inhibitor 23 23 Terapi Terapi supportif supportif lainnya lainnya Terapi fisik (fisioterapi) karena pasien Terapi fisik (fisioterapi) karena pasien imobilisasi cukup lama. imobilisasi cukup lama. Ventilasi Ventilasi mekanik mekanik MANAGEMENT MANAGEMENT Ventilasi Ventilasi mekanik mekanik Metabolik : Nutrisi enteral , ditambah Metabolik : Nutrisi enteral , ditambah parenteral bila perlu. parenteral bila perlu. Penggunaan inotropik dan atau Penggunaan inotropik dan atau vasopresor vasopresor Antikoagulan Antikoagulan 24 24 3 major complications cause death 3 major complications cause death Ventilatory Ventilatory restriction leading to respiratory restriction leading to respiratory Ventilatory Ventilatory restriction leading to respiratory restriction leading to respiratory complication and sepsis complication and sepsis Autonomic disturbance Autonomic disturbance Stress ulcer/gastric bleeding Stress ulcer/gastric bleeding 25 25 DHF GR III DHF GR III--IV (DSS) IV (DSS) DHF GR III DHF GR III--IV (DSS) IV (DSS) 26 26 DF DHF (Grades) I II III IV Febrile Phase (3-7 days) Afebrile Phase (Critical Stage) (Critical Stage) Convalescent Phase If Appropriate Treatment not provided, there is a high rist death RECOVERY Grading the Severity of Dengue Infection DF/DHF Grade* Symptoms Laboratory DF DHF DHF I II Fever with two or more of the following signs : headache, retro orbital pain, myalgia, arthalgia Above signs plus positive Tourniquet test Above signs plus spontaneous Leukopenia, Occasionally, Thrombocytopenia, may be present, no evidence of plasma loss Thrombocytopenia, < 100,000, Hct rise 20 % Thrombocytopenia, < 100,000, DHF DHF DHF II III IV Above signs plus spontaneous bleeding Above signs plus circulatory failure (weak pulse, hypotension, restlessness) Profound shock with undetectable blood presure and pulse Thrombocytopenia, < 100,000, Hct rise 20 % Thrombocytopenia, < 100,000, Hct rise 20 % Thrombocytopenia, < 100,000, Hct rise 20 % * DHF Grade III and IV are also called as Dengue Shock Syndrome (DSS) Clinical Manifestation DSS Clinical Manifestation DSS Increase of Vascular permeability : Increase of Vascular permeability : Haemoconcentration Haemoconcentration, , Hypoalbuminemi Hypoalbuminemi, , Hypoproteinemia Hypoproteinemia, Shock, Pleural , Shock, Pleural effusion effusion effusion effusion Thrombopathy Thrombopathy Coagulopathy Coagulopathy Hemorrhage 29 29 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 two seconds Profound shock with undetectable pulse and blood pressure. 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. Afebrile phase Con Phase Manifestation Profound shock with undetectable Pulse and blood pressure Manifestation 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 / mm 3 - 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 Management 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 mm 3 - 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 Fluid Therapy in DSS The policy of initial fluid therapy in DSS The policy of initial fluid therapy in DSS according to the according to the Department of Health Department of Health and WHO until 2003 : and WHO until 2003 : Crystalloid (Lactate Ringer), followed Crystalloid (Lactate Ringer), followed with colloid ( with colloid (Dextran Dextran) if not responded ) if not responded 32 32 Department of Health Department of Health Indonesian Intensive Care Association Indonesian Intensive Care Association Indonesian Anesthesiology Ass Indonesian Anesthesiology Ass Indonesian Indonesian Paed Paed. Ass (2004) . Ass (2004) Review on the management of DHF Review on the management of DHF Review on the management of DHF Review on the management of DHF Change the protocol Change the protocol Include colloid MMW Include colloid MMW--6% HES as alternative as 6% HES as alternative as initial fluid resuscitation in DSS initial fluid resuscitation in DSS 33 33 Lactated Ringer's Volume Replacement Therapy Volume Replacement Therapy Colloids Crystalloids Crystalloids HES solutions Dextran solutions Gelatin solutions Albumin PPL Lactated Ringer's Normal Saline 34 34 Crystalloid (RL, RA, Crystalloid (RL, RA, NaCL NaCL)) Distributed to the interstitial space Distributed to the interstitial space Very short period in the intravascular space Very short period in the intravascular space Very short period in the intravascular space Very short period in the intravascular space Need more fluid to maintain intravascular Need more fluid to maintain intravascular volume volume risk for interstitial edema / risk for interstitial edema / pulmonary edema pulmonary edema 35 35 HES: ( MW 100.000 HES: ( MW 100.000--300.000 300.000 kD kD ): Sealing ): Sealing effect +, effect +, good intravascular volume effect, good intravascular volume effect, longer duration in the intravascular space, longer duration in the intravascular space, Colloid Colloid DO2, DO2, VO2 VO2 Dextran Dextran : : LMW colloid (40.000 LMW colloid (40.000- -70.000 70.000 kD kD) ) with good preservation volume effect, with good preservation volume effect, no no sealing effect sealing effect, increase anaphylactic , increase anaphylactic reaction reaction 36 36 Hydroxyethyl Hydroxyethyl Starch (HES) Starch (HES) - - Effective Effective and safe plasma substitute and safe plasma substitute - - HES HES broad range of MW, from very small until broad range of MW, from very small until several hundred thousand Dalton several hundred thousand Dalton - - Classification of HES (by in vitro) according to Classification of HES (by in vitro) according to - - Classification of HES (by in vitro) according to Classification of HES (by in vitro) according to MW: MW: -- HIGH MOLECULAR WEIGHT (HMW) HIGH MOLECULAR WEIGHT (HMW) 450 K 450 K Da Da -- MEDIUM MOLECULAR WEIGHT (MMW) MEDIUM MOLECULAR WEIGHT (MMW) 200 K 200 K Da Da -- LOW MOLECULAR WEIGHT (LMW) LOW MOLECULAR WEIGHT (LMW) 70 K 70 K Da Da Sealing effect Sealing effect : HES with 100 : HES with 100 300.000 D MW 300.000 D MW Effect Effect of HES on Blood Coagulation of HES on Blood Coagulation HMW HMW--HES HES more effect on blood coagulation more effect on blood coagulation ((vWF vWF, factor VIII) , factor VIII) LMW (HES 70/0.5/4)/ LMW (HES 70/0.5/4)/MMW(HES 200/0.5/6 MMW(HES 200/0.5/6) ) did did LMW (HES 70/0.5/4)/ LMW (HES 70/0.5/4)/MMW(HES 200/0.5/6 MMW(HES 200/0.5/6) ) did did not affect on blood coagulation not affect on blood coagulation Possible Possible dilutional dilutional coagulation effect : PT, coagulation effect : PT, aPTT aPTT (significant prolongation after HMW (significant prolongation after HMW--HES 480) HES 480) Fluid Resuscitation in DSS Fluid Resuscitation in DSS Primary importance in the management Primary importance in the management of of hypoperfusion hypoperfusion state state Goal of therapy Goal of therapy Goal of therapy Goal of therapy Tissue DO Tissue DO 22 Blood Pressure Blood Pressure VO VO 22 Reversing Lactic Acidosis Reversing Lactic Acidosis Colloid Colloid MMW MMW 39 39 Study on DSS using colloid (HES ) Study on DSS using colloid (HES ) as initial fluid resuscitation as initial fluid resuscitation Tatty E. Tatty E. Setiati Setiati Different RESULT Tatty E. Tatty E. Setiati Setiati (2000) (2000) Herminia Herminia L. L. Cifra Cifra (2001 (2001) H ) H RESULT Different method of study 40 40 RL group Colloid group (HAES Steril 6%) Duration of shock ( Hour) 7.9+/- 2.6 2.3 +/- 2 Ventilators days 8 +/- 1.1 4.0 +/- 0.71 Pleural effusion 30 M2/Mod7/S21 _ ALI /PaO2/FiO2=200-250 4 1 ARDS PaO2/FiO2 < 200 6 2 Conclusion Conclusion Evidenced showed that endothelial dysfunction Evidenced showed that endothelial dysfunction lead to vascular leakage and lead to vascular leakage and hemostatic hemostatic disturbances occurred in DSS disturbances occurred in DSS MMW which has a sealing effect could MMW which has a sealing effect could MMW which has a sealing effect could MMW which has a sealing effect could minimizing vascular leakage, good preservation minimizing vascular leakage, good preservation volume effect, and lowering mortality volume effect, and lowering mortality MMW HES can be used as alternative for initial MMW HES can be used as alternative for initial fluid resuscitation in DSS fluid resuscitation in DSSS S 42 42 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. 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. 43 43 Signs of Recovery Stable pulse, blood pressure and breathing rate Normal temperature No evidence of external or internal bleeding Return of appetite Return of appetite No vomiting Good urinary output Stable haematocrit Convalescent confluent petechiae rash 44 44 SEVERE MALARIA SEVERE MALARIA SEVERE MALARIA SEVERE MALARIA 45 45 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 : 46 46 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 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) 47 47 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 48 48 WHO MULTICENTER STUDY ON SEVERE MALARIA IN UNDER WHO MULTICENTER STUDY ON SEVERE MALARIA IN UNDER FIVES IN 10 AFRICAN COUNTRIES (1230 CASES, 1999 FIVES IN 10 AFRICAN COUNTRIES (1230 CASES, 1999 2000) 2000) PREVALENCE OF SIGNS AND SYMPTOMS PREVALENCE OF SIGNS AND SYMPTOMS SIGNS AND SYMPOMS NUMBER % SEVERE ANEMIA 666 54.1 SEVERE ANEMIA 666 54.1 PROSTRATION 371 30.2 CONVULSIONS 279 22.7 CEREBRAL MALARIA 218 17.7 HYPOGLYCEMIA 162 13.2 HYPOGLOBINURIA 41 3.3 JAUNDICE 21 1.7 RESPIRATORY DISTRESS 12 1.0 DISSEMINATED INTRAVASCULAR 1 0.08 COAGULATION 49 49 Different clinical manifestation between adults and children with severe malaria Adult Children Cough Uncommon early symptom Common early symptom Convulsions Indicate cerebral involvement May indicate cerebral involvement or hypoglycemia, but may be non specific consequence of fever Duration of symptoms Commonly several days Usually 1 2 days only before features of severe before features of severe disease develop Jaundice Common Uncommon Time from start of Usually quinine 2 4 days Usually 1 2 days treatment to resolution of coma in cerebral malaria Hypoglycemia Relatively uncommon Common Usually quinine-induced (especially in pregnancy) Pulmonary edema Common Rare Renal failure Common Rare Neurological sequelae Uncommon Occur in about 10% of cases after cerebral malaria Management Management Parenteral antimalarials. IV fluid administration. Vital signs monitoring every 4 hours. Blood check up for malaria parasite every day until disappearance of parasitemia. 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. 51 51 Antimalarial drug doses in severe malaria Hospital ICU Health Clinic : No Intravenous Infusion Possible Rural health clinic : No injection facilities 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 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 Artesunate rectocap : 10 mg/kg daily Artemisinin suppository 20 mg/kg at 0 and 4 h Then daily Chloroquine sensitive P falcipanum 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 Chloroquine 10 mg base/kg Infused iv at constant rate over 8 hr followed by 15 mg base/kg over 24 hr 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 Deep Coma Repeated convulsions Respiratory distress (rapid, deep, laboured, stertorous, breathing often with intercostals recession) Significant bleeding Laboratory findings Biochemistry Hypoglycemia < 2.2 mmol/l Hyperlactatemia > 5 mmol/l Acidosis arterial pH<7.3 venous plasma HCO 3 < 15 mmol/l Serum creatitine >265 mol/l Total bilirubin > 50 mol/l Liver enzymes SGOT (AST) x 3 upper limit of normal SGPT (ALT) x 3 upper limit of normal 5 Nucleotidase Muscle enzymes CPK Myoglobin Urate > 600 mol/l Urate > 600 mol/l Hematology Leucocytosis >12.999/l Severe anemia PCV < 15 % Coagulopathy 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 55 55