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- 1. CRRT(Continuous Renal Replacement Therapy) with Case Reports (Timing,treatment modalities,general settings) Assist. Prof. Dr.Yusuf Savran Dokuz Eylul University Internal Medicine ICU
- 2. Case- 1 58 years-old male with diagnosed Type 2 Diabetes mellitus, hypertension and COPD Sepsis secondary to pneumonia Multiorgan failure including oliguric acute renal insufficiency Mechanically ventilated 0.15μg/kg/dk norepinephrine infusion needed to resume systolic blood pressure > 60 mmHg
- 3. Case - 2 35 years-old male Crash injury in earthquake Splenic rupture, splenectomy performed. Perop. 10 units erythrocyte suspension Bilateral fasciothomy applied to both lower extremity due to compartment syndrome Severe rabdomyolisis , ARF (CK: 10000,Creatinin:12 mg/dl) Severe metabolic acidosis TA:85/50 mmHg despite inotropic support (Dopamin10 mcg/kg/dk)
- 4. Case-3 50 years-old female with no comorbidity Multilobar pneumonia ARDS,Septic shock and MOF development 24 hours after initiation of antibiotherapy Metabolic acidosis Mechanical ventilation NE: 0.5 mcg/kg/dk infusion needed to resume MAP >60 mmHg
- 5. Case - 4 70 years-old male operated for left femur neck fracture Discharged - Acute respiratory distress 1 weeks later TA:70/40 mmHg, ABG:ph:7.25 pO2:60 pCO2:20 HCO3:12 Sa02:88% Thorax BT Angiography:Massive PTE Oliguric Creatinine:3.5 mg/dl (creat:1.0 mg/dl 1 week ago)
- 6. Case - 5 40 years-old female Bipolar disorder on Lithium treatment Commits suicide by 50 tablets Lithium ingestion Unconscious TA:70/40 mmHg Glasgow score :6 Severe arrythmias (+) Aspiration pneumonia (+) MOF (anuric ,elevated liver enzymes and coagulation parameters)
- 7. Case - 6 72 years-old female with past history of CHD (3 vessel CABG) and CRF (low clearance) admitted to Emergency service unconscious TA:80/40 mmHg, N:160/dk arrythmic,ventilation superficial,intubated ABG Ph:7.25 PO2:58 mmHg Pco2:70 mmHg HCO3:26 SaO2:%86 Chest X-ray: Acute pulmonary edema EKG:AF with high ventricular response Cranial CT: İschemic stroke Mechanically ventilated Echo: EF:35%,PAP:35 mmHg,LV Global hypokinetic ARF on CRF(creat:1.6 mg/dl 3.2 mg/dl)
- 8. Acute renal injury in ICU Unstabile Continuous drug replacement Mechanically ventilated Unconscious Accompanying findings : Sepsis or MOF Which RRT ?
- 9. Renal Replacement Therapy Alternatives Intermittent Hemodialysis (iHD) CRRT Modalities SCUF CAVH - CVVH CAVHD - CVVHD CAVHDF - CVVHDF SLED-EDD
- 10. Disadvantages of iHD Sudden declines in plasma osmolarity UF in limited time İncrease in body temperature Inability to remove cytokines So how shall we treat ???
- 11. Why CRRT ? Similar to normal physiology: rate slow, period enhanced Better tolerance especially in hemodynamic instability Allows removal of great amounts of fluid Efficient clearance Medium and large sized solutes can be cleared more efficiently Inflammatory mediators cleared more effectively Allows supplementary replacement fluid delivery
- 12. Fluid and anticoagulation DOSE Timing of initiation Membrane
- 13. The technique and timing as well as the type of renal replacement therapy used may affect patients’ survival and recovery of renal function. 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.
- 14. INITIATION of TREATMENT WHEN?
- 15. RIFLE Criteria Curr Opin Crit Care 8: 509-514 (2002) Level of injury Outcome measures
- 16. RIFLE Stratification in Patients Treated with CRRT Bell et al, Nephrol Dial Transplant 2005 Bell et al, Nephrol Dial Transplant 2005
- 18. From RIFLE to AKIN Serum Creatinine Increase SCr ≥24.6mmol/L 2-3 folds Stage 1 Stage 2 Stage 3
- 19. The Acute Kidney Injury Network Classification ( AKIN) Crti Care 11:R31 (2007)
- 22. CRRT Modalities • SCUF- Slow Continuous Ultrafiltration Ultrafiltration • CVVH- Continuous Veno-Venous Hemofiltration Convection • CVVHD- Continuous Veno-Venous Hemodialysis Diffusion • CVVHDF- Continuous Veno-Venous Hemodiafiltration Diffusion and Convection
- 23. Convection Hydrostatic pressure causes water movement through the membrane.During this movement Pressure 1. 2. 3. time Concurrent water and solute movement Driving force: pressure gradient FMC Pazarlama Departmanı 2011 Medium and large sized molecules removed water also drags the molecules that can not be diffused .
- 25. The concentration gradient between the sides of the membrane causes the solutes to move from the dense concentration to less dense concentration. Different concentrations (effective for small molecular sizes) Solute concentration equals on both sides 1. 2. 3. Driving force: concentration gradient FMC Pazarlama Departmanı 2011 time Diffusion
- 27. SCUF (Slow continuous ultrafiltration) In case of fluid overload 6-7 L/day ultrafiltrate Blood flow rate <100 ml/dk No dialysate fluid No Replacement fluid İnconvenient for uremics and hyperkalemia Convenient for CHF UF
- 29. Hemofiltration Solute removal via convection Blood flow rate: 200-300 ml/min UF rate: 12-20 L/24 saat Replacement fluid necessary No dialysate fluid Clearance of urea 22 L/day Time > 24 hours PreD PostD UF RF
- 30. CVVHD (Hemodialysis) Solute clearance by diffusion UF rate 2-7 L/day Flow rate of dialysate fluid: 15-45 ml/dk Blood flow rate: 100-200 ml/dk No replacement fluid Clearance of urea: 24-30 L/day Dial UF
- 31. CVVHDF(Hemodiafiltration) Blood flow rate: 100-200 ml/min Flow rate of dialysate fluid: 15-45 ml/dk High removal rate of solutes (clearance of urea: 30-60 ml/min.) Clearance of solutes: % 75 dialysis % 25 hemofiltration Dial UF rate 12-20 L/day Replacement fluid in need. UF RF
- 32. Principles of CRRT clearance • CRRT clearance of solute is dependent on the following: The molecule size of the solute The pore size of the semi-permeable membrane
- 36. Principles of CRRT clearance • Small molecules easily pass through a membrane driven by diffusion and convection. • Middle and large size molecules are cleared primarily by convection. • Semi-permeable membrane remove solutes with a molecular weight of up to 50,000 Daltons. • Plasma proteins or substances highly protein—bound will not be cleared.
- 37. Membrane types and characteristics • Hemofilter membrane are composed of: High flux material Synthetic/biocompatible material • Structural design is characterized by: High fluid removal Molecular cut-off weight of 30,000-50,000 Daltons.
- 38. Semi-permeable Membrane • The semi-permeable membrane provides: An interface between the blood and dialysate compartment. • Biocompatibility minimizes: Severe patient reactions Decreases the complement activation
- 39. The decision of the type of RRT is influenced by many factors: • Availability • Experience • Catabolic state • Hemodynsmic stability • Primary goal ? Removal of excess fluid ? Removal of excess solutes ? Both?
- 40. Decision of modality If the primary goal is removal of excess fluid : SCUF, CVVHF In catabolic state and excess low molecular size solutes : CVVHD If the primary goal is removal of excess inflammatory mediators: CVVHDF
- 41. We decided on the modality … DOSE ?
- 42. The higher the ultrafiltration rate (UFR), the greater the solute clearance.
- 44. Prospective study on 425 patients - 3 groups: Study: survival after 15 days of HF stop recovery of renal function
- 45. 20mL/Kg/hr 35mL/Kg/hr 45mL/Kg/hr 15-days Survival 41% 57% 58%
- 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. Conclusions: An increased treatment dose from 20 ml/h/kg to 35 ml/h/kg significantly improved survival. A delivery of 45ml/kg/hr did not result in further benefit in terms of survival, but in the septic patient an improvement was observed. Our data suggest an early initiation of treatment and a minimum dose delivery of 35 ml/h/kg improve patient survival rate.
- 48. EIHF vs Conventional 45mL/Kg/hr for 6 hours then 20mL/Kg/hr vs 20mL/Kg/hr 28-day Survival: 55% vs 27.5%
- 49. J Am Soc Nephrol. 2008 Jun;19(6):1233-8.
- 50. CVVHDF: more may not be better CVVHDF: 20mL/Kg/Hr CVVHDF: 35mL/Kg/Hr
- 52. Intense Conventional Hemodynamic stable IHD /SLED 6x/week with Kt/V of 1.2-1.4 IHD /SLED 3x/week with Kt/V of 1.2-1.4 Hemodynamic unstable CVVHDF 35mL/Kg/Hr CVVHDF 20mL/Kg/Hr
- 53. 60 days mortality Intensive: 53.6% Less Intensive: 51.5%
- 56. Randomized (Post-dilution CVVH) 1508 Low dose (25ml/Kg/hr) 761 High dose (40ml/Kg/hr) 747 Lost to follow up = 1 Consent withdrawn = 2 Consent not obtained = 23 Analyzed 722 Lost to follow-up = 0 Consent withdrawn = 2 Consent not obtained = 16 Analyzed 743
- 57. RENAL Study High Intensity Low Intensity 90-days mortality 44.7% 44.7% 28-days mortality 38.5% 36.5%
- 58. What have we learned about doses ? Before the ATN trial CRRT: 35mL/kg/hr Daily iHD After the ATN trial SOFA 0-2: 3x/week iHD (Kt/V 1.2) SOFA 3-4: CRRT 20 mL/kg/hr or SLED 3x/week
- 59. In Summary Decide on the treatment modality according to the primary goal Start treatment as early as possible Decide on the dose for every patient individually
- 60. Thank you…
Editor's Notes
- -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 &lt;number&gt;
- &lt;number&gt; 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.
- &lt;number&gt;
- -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;
- &lt;number&gt; 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.
- &lt;number&gt; 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.
- &lt;number&gt; 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.
- &lt;number&gt; 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.
- &lt;number&gt; 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).
- &lt;number&gt; 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.
- &lt;number&gt; 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.
- &lt;number&gt; 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.
- &lt;number&gt; 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.
- &lt;number&gt; 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) &lt;number&gt;
- &lt;number&gt; 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.
- &lt;number&gt; 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!
- 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) &lt;number&gt;
- -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 &lt;number&gt;
- -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)) &lt;number&gt;
- &lt;number&gt;