Resuscitation of Sepsis Conseps ; Early Goals-Directed Therapy (EGDT) vs Conseps EGDT ; Pola Kita / Konvensional Synopsis DISERTASI DR Basrul Hanafi
[email protected] Division of Digestive Surgery, Faculty of Medicine Padjadjaran University / Hasan Sadikin General Hospital Bandung
Background
The Surviving Sepsis Campaign’s mission is to increase awareness and improve outcome in severe sepsis (www.survivingsepsis.org)
Early Goal-Directed Therapy Results 28-day Mortality 60 50
49.2%
40
P = 0.01* 33.3%
30
20 10 0
Standard Therapy n=133
EGDT n=130
*Key difference was in sudden CV collapse, not MODS
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
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
Acute ↓ DO2 •Anemia •Hypoxemia •CO↓
OO ==25% 50% 2ER 2ER
SvO2 ↓ 50%
VO2
O2 return ↓ 500
Study design SIRS criteria SBP < 90 mmHg Lactate > 4 mmol/L
Assessment and consent Standard Therapy in ED (n=130)
Randomization (n=263)
Vital sign, Lab data, cardiac monitoring, pulse oximetry, Urinary catheterization, arterial and venous catheterization
CVP 8-12 mmHg MAP ≥ 65 mmHg
Early goal-directed therapy (n=133)
Standard care
CVP 8-12 mmHg
Continuous SvO2 monitoring and EGDT for 6 hours
Urine ≥ 0.5 cc/kg/min
MAP ≥ 65 mmHg Urine ≥ 0.5 cc/kg/min ScvO2 ≥ 70%
Hospital admission SaO2 ≥ 93% Vital sign, lab data, obtained every 12 hour for 72 hour Did not complete 6 hour (n=14)
Follow up
Hematocrit ≥ 30% Cardiac index Did not complete 6 hour (n=13)
VO2
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’
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. ii. iii. iv.
Tingkat Kesadaran Tensi Nadi Diuresis/menit
Sehingga Diketahui Tingkat Dehidrasi : R/S/B
Prognosis Peritonitis Umum e.c Perforasi; Ileum demam tifoid dan appendisitis Hanafi, (Ropanusuri 1979)
Faktor Penentu Prognosis : 1. Perforasi-operasi Interval i. ii. iii.
iv.
Interval < 24 jam, Interval 24-48 jam, Interval 49-72 jam, Interval >72 jam,
Mortality 4 % Mortality 25% Mortality 50% Mortality > 75%
Prognosis Peritonitis Umum e.c Perforasi Ileum demam tifoid Hanafi (Ropanusuri 1979) Keadaan Umum Pre Op (Setelah Resusitasi)
i.
ii. iii.
KU baik, KU sedang KU tetap buruk pasca Resusitasi,
Mortality < 5 % Mortality 25 % Mortality mendekati 100 %
Upayakan KU Baik, EGDT Pola Kita Sejak 1979
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
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
Noninvasive Monitoring (HOTMan System)
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
Noninvasive Monitoring (HOTMan System)
Noninvasive Monitoring (HOTMan System)
Konsep Rivers (2002) Balanced DO2 and VO2 through Balancing
Cardiac Preload, Contractility, and Afterload
Cardiac preload
Cardiac after load
Cardiac contractility
Balance between DO2 and VO2 Resuscitation end points SvO2
Surrogate for cardiac index
Lactate
Base deficit
Target for hemodynamic
pH
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
Siegel’s State of SIRS
The Stages of SIRS Fry ‘s Concepts, 2000
Stages
COP
SVR
A : Transient
N
N
B : MODS
C : Decompensation N D : Terminal
Lactate Org F
Konsep Tingkat Kekacauan Fisiologik vs The Stages of SIRS
I.
Stages of SIRS : i. ii. iii.
II.
Invasive Hemodynamic Systemic Parameters (COP, SVR) Severals End Organ Functions (Renal, Liver, etc) Blood Lactate
Tingkat Kekacauan Fisiologik i. ii. iii.
Noninvasive Hemodynamic Systemic Parameters (CI, SSVRI, EDI) Renal Function (Creatinine Clearence CCr 2 Hours) Blood Lactate (Lactat Pro R/)
Variabel Tingkat Kekacauan Fisiologik
I.
Hemodinamik (Noninvasif) Cardiac Index (CI) = Contractility / Pump Function ii. Stroke Systemic Vascular Resistence Index (SSVRI) = Afterload iii. End Diastolic Index (EDI) = Preload i.
II.
Rapid Creatinine Clearence
III.
Blood Lactate
Tingkat Kekacauan Fisiologik A/B/C/D or 1/2/3/4 (Numerik Katagorisasi dan Numerik Asli)
Variabel Tingkat Keadaan Umum I.
Tingkat Kesadaran
II.
Jumlah Diuresis per jam
III.
Hemodinamik Sistemik Konvensional Heart Rate (HR) ii. Mean Arterial Pressure (MAP) iii. Systemic Blood Pressure (Syst BP) i.
Apakah Keadaan Umum : Baik, Sedang, Buruk (Numerik Asli dan Numerik Katagorisasi)
Kesetaraan CCr 24 Hours vs CCr 22 Hours
Kesetaraan CCr 22 Hours vs CCr 2 Hours
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
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 sebagai Petanda asidosis !!!
Matrix Cause & Effect Cause
Activators •Soft Ts Inj •Micro-org •Endotoxin •I-Reperfusion
Effect
New Effect
HS CCr Lactate
HS CCr Lactate
Stage of SIRS A/B/C/D
New Stage of SIRS
Goals Th/ New Method vs Existing Method Randomized Intervention Study Baseline data I. II.
New Goals : Normalization of CI, SSVRI, EDI Existing : Normalization of KU
Hasil Penelitian Simpulan dan Rekomendasi
Hasil Penelitian Pria Wanita
Usia Usia (tahun) (tahun) < 20 21 – 30 31 - 40 >41
Konvensional
19
13
6
Perforasi Appendik
16
10
6
5
3
4
4
Perforasi Tifoid
3
3
-
-
-
2
1
Noninvasive
18
16
2
Perforasi Appendik
13
11
2
-
5
5
3
Perforasi Tifoid
5
5
-
2
2
1
Tidak berbeda bermakna umur, sex, etiologi antar kelompok
Hipotesis 1 Kelompok RTNI lebih baik dari RTSK dalam memperbaiki KF (Kekacauan Fisiologik)
Analisiis Multivariate KFKatagorisasi Test Effect Intercept Groups R1 R1*Groups
Wilks Wilks Wilks Wilks
Univariet WW WW*RTNI vs RTSK
Value
F
0.012288 498.3482 0.790574 1.6424 0.385529 2.2314 0.386993 2.2176
CI 0.0461* 0.1220
EDI 0.1646 0.0994
Effect Error p df df 5 31 0.000000 5 31 0.178204 15 21 0.044821 15 21 0.046044
SSVRI 0.0446* 0.0039**
Lactate 0.0347* 0.8491
CCr 0.0007* 0.0003*
Hipotesis 1 Kelompok RTNI lebih baik dari RTSK dalam memperbaiki KF (Kekacauan Fisiologik) Analisis Multivariet KF Antar Kelompok RTNI vs RTSK p=.04604 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 Resus Jam ke 12 Jam ke 48 Jam ke 00 Jam ke 24
Ke lom pok RTNI
Resus Jam ke 12 Jam ke 48 Jam ke 00 Jam ke 24
Ke lom pok RTSK
CI EDI SSVRI Lactate CCr
Hipotesis 2 Penilaian Keberhasilan Terapi KF Paralel dengan KU
Jam ke-00 Jam ke-12 Jam ke-24 Jam ke-48
Korelasi (R) 0.8322 0.8102 0.9372 0.8456
Nilai p 0.0000 0.0001 0.0000 0.0000
Hipotesis 3 Nilai Bobot Diagnostik TKF Lebih Kuat dan lebih banyak
parameternya dari TKU
Periode Jam ke-00 Jam ke-12 Jam ke-24 Jam ke-48
Parameter HR 00 MAP 00 Sist 00 HR 12 MAP 12 Sist 12 HR 24 MAP 24 Sist 24 HR 48 MAP 48 Sist 48
Root1 0.9874 -0.2757 0.1547 -1.0057 0.1594 0.0597 -0.9783 -0.1386 -0.0526 -0.9017 -0.5168 0.2745
Root1 -0.1430 -1.9162 1.1375 -0.0809 -0.7533 -0.2573 -0.2090 0.7315 0.3025 -0.3115 1.9205 -2.4969
Root1 -0.3533 1.6345 -2.3221 -0.0349 -1.9055 2.0401 -0.0195 1.3812 -1.5382 0.4950 -1.8639 1.0570
Serendipity (Hikmah terselubung)
CI ≈ MAP Variabel MAP dari KU Paralel dengan CI dari KF 120
100
80
60
40
20
0
-20 R1: 1
2
3
NI/SK: NI
4
R1: 1
2
3
NI/SK: SK
4
Cardiac Index MAP
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 !!!
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
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
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 !!
Mudah-mudahan bermanfaat untuk :
Pasien, Rumah Sakit dan Kita semua
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
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
