2. Olgu - 1
58 yaşında erkek hasta
Tip 2 Diyabetes mellitus, hipertansiyon ve KOAH
öyküsü
Pnömoniye ikincil sepsis
Çoklu organ yetmezliği ile birlikte oligurik akut
böbrek yetersizliği gelişimi
Mekanik ventilasyonda
Sistolik arteriyal kan basıncını > 60 mmHg devam
ettirmek icin 0.15μg/kg/dk norepinefrin
3. Olgu - 2
35 yaşında erkek hasta
Depremde göçük altında kalıyor
Dalak rüptürü, spenektomi uygulanıyor.
Perop. 10 ü ES replasmanı
Kompartman sendromu nedeniyle alt ekstremitelere bilateral
fasyotomi uygulanıyor.
Ağır rabdomyoliz,ABY(CK: 10000,kreatinin:12 mg/dl)
Ciddi metabolik asidoz
İnotrop desteği (Dopamin10 mcg/kg/dk) altında TA:85/50 mmHg
4. Olgu-3
Bilinen komorbid hastalığı olmayan 50 yaşında bayan
hasta
Multilober pnömoni tanısıyla servise yatırılıyor
Antibiyoterapi başlanmasından 24 saat sonra
ARDS,Septik şok ve MOF gelişiyor.
Metabolik asidoz
Mekanik ventilasyon
MAP >60 mmHg sağlayabilmek için vasopresör
ihtiyacı(NE: 0.5 mcg/kg/dk)
5. Olgu - 4
70 yaşında erkek hasta sol femur başı fraktürü nedeniyle opere
ediliyor
Taburculuğundan 1 hafta sonra akut solunum sıkıntısıyla acil
servise başvuruyor.
TA:70/40 mmHg,AKG:ph:7.25 pO2:60 pCO2:20 HCO3:12
Sa02:88%
Toraks BT Anjiografi:Massif PTE
Oligürik
Kreatinin:3.5 mg/dl(hastane taburculuğu sırasında kreat:1.0
mg/dl)
6. Olgu - 5
Bipolar bozukluk tanısı olan ve Lithium kullanmakta
olan hasta suisid amaçlı 50 adet Lithium alıyor
Yakınları tarafından Acil servise bilinci kapalı olarak
getirilen hastanın TA:70/40 mmHg Glasgow :6
Ciddi aritmileri (+)
Aspirasyon pnömonisi(+)
MOF(anürik,KCFT ve koagülasyon parametereleri
yüksek)
7. Olgu - 6
Bilinen KAH(3’lü CABG) ve KBY (düşük klirens) olan 72 yaşında
bayan hasta bilinci kapalı olarak Acil servise getiriliyor.
TA:80/40 mmHg, N:160/dk aritmik,solunum yüzeyel
AKG Ph:7.25 PO2:58 mmHg PCO2:70 mmHg HCO3:26 SaO2:%86
PA AC gr: Akut AC ödemi
EKG:HVYAF
Beyin BT: İskemik SVO
Mekanik ventilasyon desteği
EKO: EF:35%,PAB:35 mmHg,LV Global hipokinetik
KBY zemininde ABY (kreat:1.6 mg/dl 3.2 mg/dl)
8. Yoğun Bakım’da akut böbrek hasarlı olgu
Durumu unstabil
Sürekli ilaç desteği altında
Mekanik ventilatörde
Bilinci kapalı
Eşlik eden bulgular: Sepsis veya MOF
Hangi RRT ?
9. Renal Replasman Tedavi Seçenekleri
Aralıklı Hemodiyaliz Yavaş Sürekli Yöntemler
(CRRT)
SCUF
CAVH - CVVH
CAVHD - CVVHD
CAVHDF - CVVHDF
SLED-EDD
10. Hemodiyalizin sakıncaları
Plazma ozmolaritesinde azalma
Kısa sürede UF yapılması
Vücut ısısında artış
Sitokin uzaklaştırılamaması
Nasıl tedavi edelim ???
11. Neden CRRT ?
Normal fizyolojiyle benzer: hız düşük, süre uzun
Hemodinamik dengesizlikte daha iyi tolere
Fazla miktarda sıvı uzaklaştırılması mümkün
Yeterli klirens
Orta ve büyük molekül ağırlıklı solütlerin
uzaklaştırılması daha etkin
İnflamatuar mediatörlerin uzaklaştırılması daha iyi
Ek sıvı tedavileri için uygun hareket zemini
13. Renal replasman tedavisinin tekniği, zamanlaması
ve tipi hastanın yaşam süresi ve böbrek
fonksiyonlarının iyileşmesi üzerinde etkili olabilir .
Palevsky PM et al., Curr Opin Crit Care. 2005;11:548-554.
Demirkilic U, J Card Surg. 2004;19:17-20.
Swartz RD et al., Am J Kidney Dis. 1999; 34:424-432.
19. The Acute Kidney Injury Network
Classification ( AKIN)
Crit Care 11:R31 (2007)
20.
21.
22. CRRT Seçenekleri
• SCUF- Yavaş Sürekli Ultrafiltrasyon
Ultrafiltrasyon
• CVVH- Sürekli Venö-Venöz Hemofiltrasyon
Konveksiyon
• CVVHD- Sürekli Venö-Venöz Hemodiyaliz
Diffüzyon
• CVVHDF- Sürekli Venö-Venöz Hemodiyafiltrasyon
Diffüzyon ve konveksiyon
23. Hidrostatik basınç etkisiyle (yada sürükleme) su membranın bir tarafından diğer
tarafına hareket eder. Bu hareketi sırasında, difüzyonla taşınamayan molekülleri
de beraberinde sürükler.
Basınç
1. 2. 3.
zaman
Eş zamanlı su ve solüt hareketi
İtici güç: basınç farkı
FMC Pazarlama Departmanı 2011
Orta ve büyük molekül ağırlıklı
maddelerin uzaklaştırılması
Konveksiyon
24.
25. Membranın iki yanındaki konsantrasyon farkı nedeni ile solütün, konsantrasyonun
yoğun olduğu taraftan düşük olan tarafa hareketidir.
Farklı konsantrasyonlar
(küçük molekül ağırlıklı
maddeler için etkin) Membranın her iki tarafında eşit
1. 2. 3.
FMC Pazarlama Departmanı 2011
solüt konsantrasyonu
zaman
Solüt geçişi itici güç: konsantrasyon farkı
Difüzyon
26.
27. SCUF (Yavaş sürekli ultrafiltrasyon)
Sıvı fazlalığı olan olgularda
6-7 L/gün filtrat
Kan akım hızı <100 ml/dk
Diyalizat yok
Replasman sıvısı yok
Üremik ve hiperkalemiklerde
uygun değil
KKY’de uygun
UF
28.
29. CVVH(Hemofiltrasyon)
Solüt atılımı konveksiyonla
Kan akım hızı 200-300 ml/dk
UF hızı 12-20 L/24 saat
Replasman sıvısı gerekli
Diyalizat yok
Üre klirensi 22 L/gün
Tedavi süresi > 24 saat
PreD
PostD
RF
UF
30. CVVHD (Hemodiyaliz)
Amaç difüzyon ile solüt klirensi
UF hızı 2-7 L/24 saat
Diyalizat akım hızı 15-45 ml/dk
Kan akım hızı 100-200 ml/dk
Replasman sıvısı yok
Üre klirensi 24-30 L/gün
Dial
UF
31. CVVHDF(Hemodiyafiltrasyon)
Kan akım hızı 100-200 ml/dk
Diyalizat akım hızı 15-45 ml/dk
Solüt uzaklaştırılma hızı yüksek (üre
klirensi 30-60 ml/dk)
Solüt klirensinin:
% 75 diyaliz
% 25 hemofiltrasyon
UF hızı 12-20 L/24 saat
Replasman sıvısı var
PreD
PostD
RS
Dial
UF
36. CRRT Klirens Prensipleri
• Küçük moleküller difüzyon & konveksiyon
• Orta & büyük moleküller konveksiyon
• <50,000 Dalton
• Plazma proteinleri ya da yüksek oranda proteinlere
bağlanan moleküller temizlenmez.
37. Membran tipleri ve özellikleri
• Hemofiltre membranları:
Yüksek akışlı materyal
Sentetik/biyouyumlu materyal
• Yapısal tasarımları:
Yüksek miktarda sıvı uzaklaştırılması
Moleküler ağırlık sınırı: 30,000-50,000 Dalton.
38. Yarı-geçirgen membran
• Kan ve diyalizat kompartmanları arasında bir arabirim
• Biyouyumluluk :
Ciddi hasta reaksiyonlarını
Kompleman aktivasyonunu
azaltır.
39. Tedavi seçimi çok sayıda faktörden etkilenir:
Tedavinin erişilebilirliği
Klinisyenin deneyimi
Katabolik durum
Hemodinamik stabilite
Öncelikli amaç nedir?
Fazla sıvıdan kurtulmak?
Fazla solütten kurtulmak?
Her ikisi birden?
40. Tedavi Seçimi
Öncelikli hedef fazla sıvıyı uzaklaştırmak ise:
SCUF, CVVHF
Düşük MA solüt yükü fazla katabolik hastalarda:
CVVHD
Hedef inflamatuar mediatörlerin uzaklaştırılması ise:
CVVHDF
46. Effect of BUN at CVVH Initiation on Survival
80
70
60
50
40
30
20
10
0
Survivors Non Survivors
p < 0.01
Group 1 Group 2 Group 3
Blood Urea Nitrogen (mg/dl)
p < 0.01 p < 0.01
47. Sonuç:
Tedavi dozunu 20 ml/kg/s’dan 35 ml/kg/s’a çıkarmak
sağkalım üzerine belirgin etki göstermektedir.
Dozu 45ml/kg/s’a çıkarmak sağkalım anlamında ek fayda
sağlamamaktadır.
Tedaviye erken başlamak ve minimum 35 ml/kg/s
dozunda uygulamak sağkalımı belirgin arttırmaktadır.
48. EIHF vs Konvansiyonel
İlk 6 saat 45mL/kg/s sonrasında 20mL/kg/s vs 20mL/Kg/hr
28-day Survival: 55% vs 27.5%
-By a group of expert from ADQI ( Acute Dialysis Quality Initiative ) to propsoed graded definition of RIFLE criteria in 2002
-RIFLE correlated with prognosis in a number of studies
-Limitation:
--Serum Cr were strong predictors of ICU mortality but not UO criteria, remember to use the least favorable RIFLE strata
--Change in Serum Cr not directly correlate with changes in GFR
--Baseline CR is necessary to calculate the change
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This is the first study attempting to validate the RIFLE system with respect to its ability to predict mortality in critically ill ARF patients. In this retrospective study, mortality over a six month period in 223 CRRT-treated patients was assessed. Overall, acuity of illness in the patient population was quite high, with 85% of patients receiving mechanical ventilation and 78% receiving vasopressor support. The RIFLE classification effectively stratified patients according to mortality risk, with a significant survival difference observed between patients with an “R” or “I” designation and patients with a “F” and “L/E” designation. If the RIFLE approach is validated clinically in prospective studies, it will address a major shortcoming in the field of ARF and should allow for more timely and accurate diagnosis of ARF.
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-Modification of the RIFLE criteria by Acute Kidney Injury Network
-Both diagnostic and staging system
-Diagnostic criteria
--abrupt in onset within 48 hrs
--Absolute increase in serum Cr &gt;=0.3mg/dL or 26.4 mmol/L or % increase of Cr &gt;=50% or oliguric for &gt;=6 hrs
--After volume status optimised and urinary tract obstruction excluded
-Staging system
--RIFLE Loss and ESRD removed
&lt;number&gt;
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CRRT modalities contains four therapies, and we will begin by talking specifically about each therapy. CRRT is well-known by all the acronyms. Each acronym describes the therapy being performed in treating the patient. History has shown us that there are many ways to perform each therapy. However, each therapy does carry is own basic concept.
SCUF- modality is only removing patient plasma water. Does not require replacement or dialysate solution.
CVVH- modality requires replacement solution. This replacement solution drives convection.
CVVHD- is continuous form of hemodialysis and requires dialysate solution to create a concentration gradient for diffusion.
CVVHDF- hemodiafiltration requires the use of dialysate and replacement solution and uses both transport mechanisms of convection and diffusion.
Let’s take a look at the transport mechanisms related to each individual therapy.
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This visual will provide you with a better understanding of how convection works. From the picture you can see a faucet which represents replacement solution. The top faucet is an example of pre-filter dilution, which means that the replacement solution mixes with the blood as it enters the filter. The bottom faucet is an example of post-filter dilution and is delivered as the blood is returning to the patient.
Now the effluent pump is removing ultrafiltration (just like SCUF), or patient plasma water and replacement solution.
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The patients blood contains a high concentration of unwanted solutes that can be effectively removed by diffusion. Diffusions key mechanism is to move a solute from a higher concentration gradient to a lower concentration gradient.
For example, let us assume the blood in the filter has a high concentration of potassium molecules and on the fluid/dialysate compartment has a low concentration of potassium. The potassium gradually diffuses through the membrane from the area of a higher potassium concentration to the area of a lower potassium concentration until it is evenly distributed.
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Here is a visual example of how ultrafiltration works. On the blood side of the hemofilter you have a positive pressure gradient. on the fluid side of the hemofilter you have a negative pressure gradient. The effluent pump applies pressure on the membrane causing the fluid to move from the positive pressure gradient to the lower pressure gradient.
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CRRT solute clearance is dependent on the following: The size of the molecule and the pore size of the semi-permeable membrane. The best way to drive solute clearance is to increase the ultrafiltration removal rate ( combination of replacement solution and patient plasma water).
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Remember the transport of a molecule through a membrane is governed largely by its molecular weight. Generally, the more a molecule weighs, the larger it is in size and the more resistant it is to transport. The chart gives an indication of relative molecular weights for some of the common molecules that we are concerned with in CRRT. Molecular weights are measured in units called Daltons.
Small molecules &lt;300 Daltons, e.g. urea, creatinine, Na+, electrolytes
Intermediate or middle molecules 500-5000 Daltons e.g. B12
Large molecules 5000-50000 Daltons e.g. LMW proteins, beta 2 micro globulins, cytokines, myoglobin
&lt;number&gt;
Molecular size: Both molecule size and pore size determine the solute flow through the semi-permeable membrane. As you can see from this picture we have a membrane with small pores. The pink molecule represent Urea molecules, which are considered small size molecules. The green molecules represents cytokine molecules, which are considered a middle size molecules. The (pink molecule) Urea easily passes through the small pores, but the (green molecule) Cytokines are to large to move across the membrane therefore they remain in the blood.
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This picture depicts a membrane that has large pore size. As you can see from this picture we have a membrane with large pores. Again, we will say the pink molecule represent Urea molecules, and the green molecules represent a cytokine molecules. The Urea easily passes through the large pores, and the Cytokines also move across the membrane therefore they are removed from the blood.
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Back to the basic CRRT transport principles: the combination of diffusion and convection allow small molecules to easily pass through the membrane, and middle and large molecules to be driven across the filter by convection. The semi-permeable membrane allows removal of solutes with a molecular weight of up to 50,000 Daltons. Keep in mind that anything that is protein-bound will not be cleared.
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Membrane types and characteristics are other important technical considerations. Hemofilters are composed of a membrane that consists of high flux material (porous). The membrane material is usually synthetic, but very biocompatible to the patient.
Here are a few examples of high-flux membrane material:
Polysulfone (PS)
Polyamide (PA)
Polyacrylonitrile ( PAN)
AN69
The structural design of a high flux membrane is characterized by high fluid removal and typically has a molecular cut-off weight of 55,000 Daltons.
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The hemofilter contains a semi-permeable membrane that provides an interface between the blood and dialysate compartment. This interface creates a barrier so that the blood and dialysate never come in contact with each. Biocompatibility is an important feature, because the membrane’s chemical properties minimize blood’s reaction I.e. thrombocytes and/or complement activation and immune system response (allergic reaction).
&lt;number&gt;
Dr. Ronco set forth to study answer the question “What is the adequate dose for the ARF patient?” thus began the journey to find this dose. The origin of ARF was mostly post surgical with the other causes from medical and trauma related. Sepsis was also prevalent throughout the study participants. Dr. Ronco selected 492 patients for the study, but 67 of those patient were excluded. Some of the 425 patients were actually randomized into the study, and assigned to one of the three doses: 20ml/kg/hr, 35ml/kg/hr, and 45ml/kg/hr. The study was conducted using only convection therapy. All replacement solution was delivered post-filter, and UFR was used to measure dosing.
Why did he use UFR to measure dosing. Well, it is known that solute movement across the membrane is proportional to UFR. For example, Urea has a sieving coefficient of 1 it is then assumed that it is equal to UFR. Therefore, ultrafiltration rate corresponds with clearance, and can be used as a surrogate treatment dose.
-Landmark study by Ronco in a single-centre randomised trial: survival at 15 days was improved by increasing CRRT dose from 20 to 35 ml/Kg/hr
-Concern about this study:
Unblined single-centre, took 5-years to complete
Sepsis contribute to 15% vs 50-60% incidence worldwide
Cost assoc with intensifying the therapy and it is post-dilution technique
Small sample size ( 425 patients)
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At least three different studies have shown a benefit for early initiation of therapy. Ronco’s study also suggests that patient’s with significantly lower BUN at the time of CVVH initiation had better survival rates whereas the patient with high BUN’s at the time of CVVH initiation had poor survival rates. This demonstrates a powerful effect of timing of treatment initiation on outcome.
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So based on the previous slides we can conclude that a dose of 35ml/h/kg is very appropriate in a CRRT setting and in the meantime is widely accepted as a golden standard.
Besides the dose this study also indicates that TIMING seems to be another important influencing factor from an outcome perspective.
Again you should point out the quality of the study and that there is not ONE single study available at the same level. So if you want to prescribe therapy and you feel comfortable to use a widely accepted guideline… this is one!
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-Retrospective study before and after change of protocol, 40 patients before and 40 after
-EIHF: Early isovolaemic hemofiltration: MSOF in sepsis is due to a variety of immunomodulationg substanace ( humoral mediators) and HVHF can non-selectively remove a wide range of such modulators
-Treatment continue from min of 3 days to max of 9 days, median of 5 days
-Treatment group: better BP, decrease inotrope requirement and wean from MV faster and shorter ICU LOS
Published in early 2008 in J Am Soc Nephrol
-Primary outcome is survival to ICU discharge or 30-days survival: 49% ( high dose arm ) vs 56%( standard dose arm) (P=0.32)
-Among survivor, recover renal fx : 69% ( high dose arm) vs 80% (standard-dose arm)
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-Schiff_NEJM_2002: daily dialysis is better than second daily dialysis
-Two modality of treatment included and allow patient transition provided that they stick to the dose of dialysis
-Hemodynamic stable: SOFA cardiovascular score of 0-2
-For IHD/SLED: treatment intensity is adequate –up to Kt/V of 1.2-1.4
-For the CVVHDF: different from Ronco in which they use the HDF instead of HF and it is pre-dilution instead of post-dilutuion
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-Primary outcome: 60-days mortality is 53.6% ( intensive therapy) vs 51.5% ( less-intensive therapy) ( OR=1.09, P=0.47)
-No difference between the two groups in
--duration of RRT or
--rate of recovery of kidney function or
--nonrenal organ failure
&lt;number&gt;
-RENAL: Randomised Evaluation of Normal versus Augmented Level Replacement Therapy Study
Different from the ATN study
--Older patient with lower incidence of sepsis, but higher CVS and Resp SOFA
--Not RRT before randomization
--Mean time from ICU admission to randomization: 50 hrs vs 150 hrs
--Use post-dilution CVVH and only 314 session of IHD
--lower rate of dialysis dependence in this study by 28 and 90 days ( 15.8% vs 45.2% & 5.6 % vs 24.6% ( 60-days))
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