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

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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

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Background

The Surviving Sepsis Campaign’s

mission is

to increase awareness and

improve outcome in severe sepsis

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49.2% 33.3% 0 10 20 30 40 50 60 Standard Therapy n=133 EGDT n=130 P = 0.01

*

Key difference was in sudden CV collapse, not MODS

28-day Mortality

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 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

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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

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O₂ER = 25% Acute ↓ DO₂

VO

₂



O₂ER  = 50% O₂ return ↓ 500 SvO₂ ↓ 50% •Anemia •CO↓ •Hypoxemia

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Study design

SIRS criteria SBP < 90 mmHg Lactate > 4 mmol/L Assessment and consent

Randomization (n=263)

Standard Therapy

in ED (n=130) Early goal-directed therapy (n=133)

Vital sign, Lab data, cardiac monitoring, pulse oximetry,

Urinary catheterization, arterial and venous

catheterization

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 VO2 CVP 8-12 mmHg MAP ≥ 65 mmHg Urine ≥ 0.5 cc/kg/min Standard care Hospital admission Vital sign, lab data, obtained every 12 hour

for 72 hour

Follow up Did not complete _{6 hour (n=13)} Did not complete

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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’

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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

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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 24-48 jam, Mortality 25% iii. Interval 49-72 jam, Mortality 50% iv. Interval >72 jam, Mortality > 75%

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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 %

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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

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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

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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

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Konsep Rivers (2002)  Balanced DO₂ and VO₂ through Balancing Cardiac Preload, Contractility, and Afterload

Cardiac

preload after loadCardiac contractilityCardiac

Balance between DO2 and VO2

SvO2 Lactate Base deficit pH

Resuscitation end points

Target for hemodynamic Surrogate for

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Siegel

’

s Concepts (1979)

Central to the concept of physiological state

classification is the understanding that change in state occurs over time as

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The Stages of SIRS

Fry ‘s Concepts, 2000

Stages COP SVR Lactate Org F

A : Transient   N N

B : MODS    

C : Decompensation N   

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Konsep

Tingkat Kekacauan Fisiologik vs The Stages of

SIRS

I. Stages of SIRS :

i. Invasive Hemodynamic Systemic Parameters (COP, SVR) ii. Severals End Organ Functions (Renal, Liver, etc)

iii. Blood Lactate

II. Tingkat Kekacauan Fisiologik

i. Noninvasive Hemodynamic Systemic Parameters (CI, SSVRI,

EDI)

ii. Renal Function (Creatinine Clearence CCr 2 Hours) iii. Blood Lactate (Lactat Pro R/)

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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. Rapid Creatinine Clearence III. Blood Lactate

 Tingkat Kekacauan Fisiologik A/B/C/D or 1/2/3/4 (Numerik Katagorisasi dan Numerik Asli)

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Variabel

Tingkat Keadaan Umum

I. Tingkat Kesadaran

II. Jumlah Diuresis per jam

III. 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)

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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,

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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 + _{+ 2 Lactate}

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Matrix Cause & Effect

Activators •Soft Ts Inj •Micro-org •Endotoxin •I-Reperfusion

Stage of SIRS A/B/C/D

Cause _Effect

Goals Th/ New Method vs Existing Method

Baseline data

Randomized Intervention Study

New Stage of SIRS

HS CCr Lactate _{HS CCr Lactate} New Effect

I. New Goals : Normalization of CI, SSVRI, EDI II. Existing : Normalization of KU

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Hasil Penelitian

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Hasil Penelitian

Usia

(tahun) (tahun) Usia

Pria Wanita < 20 21 – 30 31 - 40 >41 Konvensional Perforasi Appendik Perforasi Tifoid 19 16 3 13 10 3 6 6 - 5 - 3 - 4 2 4 1 Noninvasive Perforasi Appendik Perforasi Tifoid 18 13 5 16 11 5 2 2 - - 2 5 2 5 1 3

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Hipotesis 1

Kelompok RTNI lebih baik dari RTSK dalam memperbaiki KF (Kekacauan

Fisiologik)

Univariet CI EDI SSVRI Lactate CCr WW 0.0461*_{0.1646 0.0446}* _0.0347* _0.0007* WW*RTNI vs RTSK 0.1220 0.0994 0.0039** _{0.8491 0.0003}*

Analisiis M ultivariate KFKatagorisasi

Effect

Test Value F Effect df Error df p Intercept Groups R1 R1*Groups Wilks 0.012288 498.3482 5 31 0.000000 Wilks 0.790574 1.6424 5 31 0.178204 Wilks 0.385529 2.2314 15 21 0.044821 Wilks 0.386993 2.2176 15 21 0.046044

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Hipotesis 1

Kelompok RTNI lebih baik dari RTSK dalam memperbaiki KF (Kekacauan

Fisiologik)

Analisis Multivariet KF Antar Kelompok RTNI vs RTSK

p=.04604 CI EDI SSVRI Lactate CCr

Ke lom pok RTNI

Resus

Jam ke 00Jam ke 12Jam ke 24Jam ke 48 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 Ke lom pok RTSK Resus

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Hipotesis 2

Penilaian Keberhasilan Terapi KF Paralel dengan KU

Korelasi (R) Nilai p

Jam ke-00 0.8322 0.0000

Jam ke-12 0.8102 0.0001

Jam ke-24 0.9372 0.0000

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Hipotesis 3

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

Periode Parameter Root1 Root1 Root1 Jam ke-00 HR 00 0.9874 -0.1430 -0.3533 MAP 00 -0.2757 -1.9162 1.6345 Sist 00 0.1547 1.1375 -2.3221 Jam ke-12 HR 12 -1.0057 -0.0809 -0.0349 MAP 12 0.1594 -0.7533 -1.9055 Sist 12 0.0597 -0.2573 2.0401 Jam ke-24 HR 24 -0.9783 -0.2090 -0.0195 MAP 24 -0.1386 0.7315 1.3812 Sist 24 -0.0526 0.3025 -1.5382 Jam ke-48 HR 48 -0.9017 -0.3115 0.4950 MAP 48 -0.5168 1.9205 -1.8639 Sist 48 0.2745 -2.4969 1.0570

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Serendipity (Hikmah terselubung)

CI ≈ MAP

Variabel MAP dari KU Paralel dengan CI dari KF Cardiac Index MAP NI/SK: NI R1: 1 2 3 4 -20 0 20 40 60 80 100 120 NI/SK: SK R1: 1 2 3 4

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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

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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

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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

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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 !!

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Mudah-mudahan bermanfaat untuk :

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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

Grading System

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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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