Resuscitation of Sepsis Conseps ; Early Goals-Directed Therapy (EGDT) vs Conseps EGDT ; Pola Kita / Konvensional

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1 Resuscitation of Sepsis Conseps ; Early Goals-Directed Therapy (EGDT) vs Conseps EGDT ; Pola Kita / Konvensional Synopsis DISERTASI DR Basrul Hanafi behanafi@gmail.com Division of Digestive Surgery, Faculty of Medicine Padjadjaran University / Hasan Sadikin General Hospital Bandung

2 Background The Surviving Sepsis Campaign s mission is to increase awareness and improve outcome in severe sepsis (

3 Early Goal-Directed Therapy Results day Mortality 49.2% 50 P = 0.01* % Standard Therapy n=133 EGDT n=130 *Key difference was in sudden CV collapse, not MODS

4 1. Initial Resuscitation Resuscitation should begin as soon as severe sepsis or sepsis induced tissue hypoperfusion is recognized Elevated Serum lactate identifies tissue hypoperfusion in patients at risk who are not hypotensive

5 Goals of therapy within first 6 hours are Recommendation : Grade B 1. Central Venous Pressure 8-12 mm Hg (12-15 in ventilator pts) 2. Mean arterial pressure > 65 mm Hg 3. Urine output > 0.5 ml/kg/hr 4. ScvO2 or SvO2 70%; 5. if not achieved with fluid resuscitation during first 6 hours: - Transfuse PRBC to hematocrit > 30% and/or - Administer dobutamine (max 20 mcg/kg/min) to goal

6 Acute DO 2 Anemia Hypoxemia CO OO 2 ER 2 ER = 25% 50% VO 2 SvO 2 50% O 2 return 500

7 Study design SIRS criteria SBP < 90 mmhg Lactate > 4 mmol/l Assessment and consent Standard Therapy in ED (n=130) Randomization (n=263) Early goal-directed therapy (n=133) CVP 8-12 mmhg MAP 65 mmhg Urine 0.5 cc/kg/min Standard care Vital sign, Lab data, cardiac monitoring, pulse oximetry, Urinary catheterization, arterial and venous catheterization Hospital admission Vital sign, lab data, obtained every 12 hour for 72 hour Continuous SvO2 monitoring and EGDT for 6 hours CVP 8-12 mmhg MAP 65 mmhg Urine 0.5 cc/kg/min ScvO2 70% SaO2 93% Hematocrit 30% Cardiac index Did not complete 6 hour (n=14) Follow up Did not complete 6 hour (n=13) VO2

8 EGDT vs Resusitasi Terkendali Rivers (2002) : Early Goals Directed Therapi Penilaian keberhasilan terapi APACHE II Hanafi (1979) : Upaya perbaiki terlebih dulu KU pre operatif agar KU Baik atau KU Sedang Menghasilkan Prognosis lebih baik Telah Merupakan Konsep Kita Bersama disebut Resusitasi Pola Kita, Eksis Sudah Lama Resusitasi Konsep Kita Bersama itu Apakah Benar? Sehingga Perlu Diteliti Resusitasi bersasaran terapi / Terkendali arahnya Penilaian keberhasilan terapi KU Baik / Sedang

9 Keadaan Umum (KU) : KU pasien yg akan dioperasi, perlu disiapkan secara baik Bila terdapat syok, dikoreksi terlebih dulu Cara Mengoreksi : Penilaian Tingkat Dehidrasi : Dehidrasi Ringan (R), Sedang (S), Berat (B) Parameternya : i. Tingkat Kesadaran ii. Tensi iii. Nadi iv. Diuresis/menit Sehingga Diketahui Tingkat Dehidrasi : R/S/B

10 Prognosis Peritonitis Umum e.c Perforasi; Ileum demam tifoid dan appendisitis Hanafi, (Ropanusuri 1979) Faktor Penentu Prognosis : 1. Perforasi-operasi Interval i. Interval < 24 jam, Mortality 4 % ii. Interval jam, Mortality 25% iii. Interval jam, Mortality 50% iv. Interval >72 jam, Mortality > 75%

11 Prognosis Peritonitis Umum e.c Perforasi Ileum demam tifoid Hanafi (Ropanusuri 1979) Keadaan Umum Pre Op (Setelah Resusitasi) i. KU baik, Mortality < 5 % ii. KU sedang Mortality 25 % iii. KU tetap buruk pasca Resusitasi, Mortality mendekati 100 % Upayakan KU Baik, EGDT Pola Kita Sejak 1979

12 THE NON-INVASIVE AND STANDARD GOAL-DIRECTED RESUCITATION METHOD IN CONTROLING PHYSIOLOGIC DERANGEMENT OF SECONDARY GENERALISED PERITONITIS METODE RESUSITASI TERKENDALI STANDAR DAN NONINVASIF SEBAGAI PENGONTROL KEKACAUAN FISIOLOGIK PADA PERITONITIS UMUM SEKUNDER Basrul Hanafi, 2004

13 Shoemaker s Concept (New Horizon, 1996 ) Early Physiologic Patterns in Acute Illness and Accidents : Toward a Concept Circulatory Dysfunction and Shock Based on Invasive and Noninvasive Hemodynamic Monitoring. We concluded that noninvasive measurements identify early circulatory problems reliably and provide objective criteria for physiologic analysis as well as for definition of therapeutic goals and titration of therapy

14 Noninvasive Monitoring (HOTMan System)

15 Sramek s Concept (1998) Interactive Noninvasive Monitoring of Hemodynamic Systemic and Oxygen Transport Parameters with 14 variables Simulation and Titration Therapy Therapeutic Goals (Goals-Directed Therapy) without Trial and Error

16 Noninvasive Monitoring (HOTMan System)

17 Noninvasive Monitoring (HOTMan System)

18 Konsep Rivers (2002) Balanced DO 2 and VO 2 through Balancing Cardiac Preload, Contractility, and Afterload Cardiac preload Cardiac after load Cardiac contractility Balance between DO2 and VO2 Resuscitation end points SvO2 Lactate Base deficit ph Surrogate for cardiac index Target for hemodynamic

19 Siegel s Concepts (1979) Central to the concept of physiological state classification is the understanding that change in state occurs over time as the patient s condition improves or worsens

20 Siegel s State of SIRS

21 The Stages of SIRS Fry s Concepts, 2000 Stages COP SVR Lactate Org F A : Transient N N B : MODS C : Decompensation N D : Terminal

22 Konsep Tingkat Kekacauan Fisiologik vs The Stages of SIRS I. Stages of SIRS : i. Invasive Hemodynamic Systemic Parameters (COP, SVR) ii. iii. Severals End Organ Functions (Renal, Liver, etc) Blood Lactate II. Tingkat Kekacauan Fisiologik i. Noninvasive Hemodynamic Systemic Parameters (CI, SSVRI, EDI) ii. iii. Renal Function (Creatinine Clearence CCr 2 Hours) Blood Lactate (Lactat Pro R/)

23 Variabel Tingkat Kekacauan Fisiologik I. Hemodinamik (Noninvasif) i. Cardiac Index (CI) = Contractility / Pump Function ii. Stroke Systemic Vascular Resistence Index (SSVRI) = Afterload iii. End Diastolic Index (EDI) = Preload II. III. Rapid Creatinine Clearence Blood Lactate Tingkat Kekacauan Fisiologik A/B/C/D or 1/2/3/4 (Numerik Katagorisasi dan Numerik Asli)

24 Variabel Tingkat Keadaan Umum I. Tingkat Kesadaran II. III. Jumlah Diuresis per jam Hemodinamik Sistemik Konvensional i. Heart Rate (HR) ii. Mean Arterial Pressure (MAP) iii. Systemic Blood Pressure (Syst BP) Apakah Keadaan Umum : Baik, Sedang, Buruk (Numerik Asli dan Numerik Katagorisasi)

25 Kesetaraan CCr 24 Hours vs CCr 22 Hours

26 Kesetaraan CCr 22 Hours vs CCr 2 Hours

27 Marker of Alteration Energy Metabolism (Satsharma, 2001) Hypoxia : Reduced Pyruvat production into Krebs cycle, Increased Lactate production Blood Lactat concentration parallel, with : total oxygen debt, magnitude of hypoperfusion, and the severity of shock, Increased H + load

28 Blood Lactate Sat Sharma (2001) Hydrolysis 1 ATP = 1 ADP + Energy + 1 H + Glycolysis Aerobic : 1 Molecule Glucose dihasilkan 36 ATP + Pengikatan Kembali 36 H + Glycolysis Anaerobic : 1 Molecule Glucose dihasilkan 2 ATP + 2 Lactate + terlepas 2 H + Metabolic Acidosis : Akibat tidak terikat 2 H Lactate sebagai Petanda asidosis!!!

29 Matrix Cause & Effect Cause Effect New Effect Activators Soft Ts Inj Micro-org Endotoxin I-Reperfusion HS CCr Lactate Stage of SIRS A/B/C/D HS CCr Lactate New Stage of SIRS Goals Th/ New Method vs Existing Method Baseline data Randomized Intervention Study I. New Goals : Normalization of CI, SSVRI, EDI II. Existing : Normalization of KU

30 Hasil Penelitian Simpulan dan Rekomendasi

31 Hasil Penelitian Pria Wanita Usia (tahun) Usia (tahun) < >41 Konvensional Perforasi Appendik Perforasi Tifoid Noninvasive Perforasi Appendik Perforasi Tifoid Tidak berbeda bermakna umur, sex, etiologi antar kelompok

32 Hipotesis 1 Kelompok RTNI lebih baik dari RTSK dalam memperbaiki KF (Kekacauan Fisiologik) Analisiis Multivariate KFKatagorisasi Effect Intercept Groups R1 R1*Groups Test Value F Effect df Error df p Wilks Wilks Wilks Wilks

33 Hipotesis 1 Kelompok RTNI lebih baik dari RTSK dalam memperbaiki KF (Kekacauan Fisiologik) 4.5 Analisis Multivariet KF Antar Kelompok RTNI vs RTSK p= Resus Jam ke 12 Jam ke 48 Jam ke 00 Jam ke 24 Kelom pok RTNI Resus Jam ke 12 Jam ke 48 Jam ke 00 Jam ke 24 Kelom pok RTSK CI EDI SSVRI Lactate CCr

34 Hipotesis 2 Penilaian Keberhasilan Terapi KF Paralel dengan KU Korelasi (R) Nilai p Jam ke Jam ke Jam ke Jam ke

35 Hipotesis 3 Nilai Bobot Diagnostik TKF Lebih Kuat dan lebih banyak parameternya dari TKU

36 Serendipity (Hikmah terselubung) CI MAP Variabel MAP dari KU Paralel dengan CI dari KF R1: NI/SK: NI R1: NI/SK: SK Cardiac Index MAP

37 Simpulan Umum 1. RTNI lebih baik menormalkan hemodinamik sistemik, fungsi ginjal, dan kondisi metabolik dibandingkan RTSK 2. Kemampuan Diagnostik KF sejajar dengan KU 3. TKF lebih kuat bobot diagnostiknya dan lebih banyak Parameternya dibandingkan TKU 4. Upaya Normalisasi Parameter Hemodinamik Sistemik, Fungsi Ginjal dan Metabolik melalui panduan manapun (RTNI atau RTSK) dapat Memperbaiki KF dan KU, merupakan suatu Konsep Baru dan Bukti Baru bahwa Cara Konvensionalpun dapat diandalkan, asalkan dilakukan secara seksama!!!

38 Simpulan Khusus 1. Fungsi Ginjal CCr 2 hours jauh lebih dapat diandalkan dibandingkan Diuresis per Jam sebagai Petanda Baik Respons Tindakan Resusitasi 2. Kadar Laktat Darah juga dapat diandalkan sebagai Petanda Baik Respons Tindakan Resusitasi 3. MAP CI

39 Saran Praktis 1. Kembali Normalnya Parameter Hemodinamik Sistemik CI, EDI, SSVRI, dan HR, MAP, Syst BP dapat dipakai sebagai Guidlines (Protap) panduan resusitasi. 2. Penilaian CCr 2 hours dan Blood Lactate dan Tingkat Kesadaran Sadar serta Diuresis > 50 ml / Jam, dapat dipakai sebagai panilaian Fungsi Organ dan Gangguan Metabolik yang Efektif, Sederhana, dan Terjangkau

40 Implikasi di Lapangan Menggunakan Metode manapun (RTNI atau RTSK) asalkan Terpantau Baik, hasilnya juga baik!! Pada Penelitian ini, mortality / angka kematiannya 0% Penelitian pada peritonitis sekunder (hanya Sepsis Intraperitoneal) Belum diteliti pada Severe Sepsis dan Septic Shock Metode RTSK dan Penilaian KU ditambah CCr 2 hours serta Blood Lactate Mudah Diterapkan Penerapannya di RS Manapun, akan Berdampak Positif Bagi Seluruh Pasien!!

41 Mudah-mudahan bermanfaat untuk : Pasien, Rumah Sakit dan Kita semua

42 Grading System Evidence Based Medicine Grading of Recommendations A. Supported by at least two level I investigations B. Supported by one level I investigation C. Supported by level II investigations only D. Supported by at least one level III investigation E. Support by level IV or V evidence

43 Level of Evidence and Recommendation : EGDT Pola Kita : Teruji Juga Baik Hasilnya Asalkan Diterapkan Secara Benar!!! Level of Evidence : Randomized Study Small Sample Size Rekomendation : Grade B

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