Indications. Claire Stigare

Transcription

1 Indications Claire Stigare

2 Fall S: 70 yr old man. ARDS (unknown cause) after CABG + MR B: Previously healthy (HT), creatinine 90 (baseline) A: NIV 5 days, treatment of failure, simdax, furix, sudden deterioration, C: ST 100/min, Norad 0,28 ug/kg/min. lak 1.5, Hb 96 R: Intubated. PC Hypercapnea PCO2 10, ph 7,1 Pa02 9 (Fio2 0,7) Bilateral ground glass appearance, CT chest, Signs of pulmonary odema N: Creatinine 200, urea 19, Cystatin C 2,2, diuresis /ml/day Cumulative fluid balance -5l since admission but today + 2.5L Coag: INR 3,5 (warfarin) Infection: Low Pct, CRP 200, all cultures negative

3 Do you see any role for CRRT in this patient? If so what are the indications?

4 Indications Classic, extended Renal / non renal Suggested indications, what evidence do we have?

5 International guidelines? KDIGO Kidney Disease Improving global outcomes

6 Classic /conventional indications Renal Support in critical illness. Bagshaw et al. J Can Anesth (2010) 57:

7 Extended indications Immunomodulation sepsis, ARDS & after ECC Poisons Rhabdomyolysis Tumour lysis syndrome- chemotherapy ARDS? Abdominal compartment syndrome Cardiac arrest Hypo and hyperthermia Dysnatremia Lactic acidosis Multi-organ failure

8 Classic indications Evidence for given parameters?

9 Azotemia blood urea nitrogen level. No universally accepted level of urea at which to start CRRT Rate of rise may be important

10 1mg/dl = 2.8mmol/l 100 = 35mmol/l 21mmol/l 27mmol/l

11 Bagshaw et al. Journal of critical care (2009) 24, Prospective multicentre observational study. 23 countries 1238 patients. Results: RRT timing by S urea conc (</> 24.2mmol/l) showed no diff in crude hospital or covariate adjusted mortality. Stratification by creatinine (</> 309umol/l). Late rrt was associated with lower crude (53.4% vs 71.4% OR %CI 0,36-0,58 P< 0.001) and covariate mortality (OR, 0,51; 95% CI P<0.001). Timing relative to ICU admission early (<2 days), delayed and late(>5 days). Late initiation was associated with greater crude (72.8% vs 62.5% vs 59% P<0.001) and covariate adjusted mortality (OR, 1.95 CI, , P=0.001). Overall late RRT was associated with al longer duration of RRT, hospital stay and dialysis dependence.

12 Acidosis

13 Metabolic acidosis ( due to renal failure) Minskad utsöndring av sulphat och fosfat. Minskad kapacitet av tubuli att utsöndra att producera ammoniak

14 <ph 7.15? This cut off was used in surviving sepsis campaign. Dellinger 2004, 2008 and by AKIN group. Bicarbonate not shown to be beneficial when given to patients at ph < Cooper et al Bicarbonate does not improve haemodynamics in critically ill patients who have lactic acidosis: a prospective, controlled clinical study. Ann Intern Med 112: Mathieu et al Effects of bicarbonate therapy on haemodynamics and tissue oxygenation : a prospective, controlled clinical study. Critical care Med 19:

15 AKIN surviving sepsis Dellinger ICU Survivors (n=848) ICU Non-survivors (n=999) P

16 Anuria/oligouria (<400ml/day)

17 UK ICU database (ICNARC) Severe AKI (S Crea >300umol/l +/or Urea >40mmol/l) 17,326 patients. Oligoruric AKI (<400ml/24hrs) associated with significantly higher ICU and hospital mortality (55.8% and 70.3%) compared with non oligouria AKI (33.4% and 49.3%).

18 Retrospective analysis of 1,847 AKI patients with RRT in 22 ICUs in UK and Germany. Analysis of characteristics of patients at initiation of RRT. Significant difference in mortality between patients with: Oligouria (<400ml/24hrs) = 59% Urine production greater than 400ml/24hrs = 47.4%. P<

19 Rain picture Fluid overload

20 Fluid overload has a negative impact on clinical outcome in: 1. Critically ill patients. Alsous (septic shock), Sakr (ALI), Upadaya (weaning) 2. Critically ill patients with AKI. (Bagshaw, Bouchard, Payen) Payen 2008 SOAPS 3147 pts. AKI daily fluid balance significantly more positive among non survivors than survivors. 1l vs. 0,15l. p< Children with AKI. Clear association between fluid overload, and mortality in children on RRT with AKI.

21 Fluid overload in Adults with AKI 1. Heung, M. Nephrology, dialysis, transplantation Mar;27(3): RRT AKI patients. Recovering patients had significantly less fluid overload at the time of RRT initiation compared to non-recovering patients (3.5% versus 9.3%, P = 0.004). 2. Finnaki, Vaara Crit Care Oct 17;16(5):R RRT patients with AKI Fluid overload (FO) = cumulative balance >10% of baseline weight. Crude 90 day mortality with (FO) 59.2%, without FO 31.4% p< Logistic regression:fo at RRT initiation twice as high crude 90 mortality compared with those without FO (OR 2.6).

22 Extended indications Immunomodulation sepsis, ARDS & after ECC Poisons refractory respiratory acidosis in ARDS Tumour lysis syndrome- chemotherapy Rhabdomyolys Abdominal compartment syndrome Cardiac arrest Hypo and hyperthermia Dysnatremia (Na >160mmol/L) Lactic acidosis Prevention of contrast nephropathy

23 Sepsis

24 Sepsis - immunomodulation Inflammatory mediators size: 5-50kDa. Aim: non selective reduction of pro and anti inflammatory mediators & removal of endotoxin. -assumes fall in blood cytokine levels beneficial Possible uses: SEPSIS, ARDS, post cardiopulmonary bypass Methods: high flow hemofiltration convection- molecules up to 30kDa use of filters with high adsorptive capacity >30KDa

25 High flow haemofiltration Kellum. Crit Care Med. 1998, 26: Result: Only haemofiltration, not haemodialysis reduced TNF a levels. Ronco THE LANCET Vol 356 July 1, RCT 425 AKI patients. Result: Significantly better survival in patients receiving higher doses 35 & 45ml/kg/hr versus 20ml/kg/hr

26 Therapy Dose in CVVH 45 ml/kg/hr 35 ml/kg/hr 25 ml/kg/hr Ronco, C et al. Lancet 2000; 355: 26-30

27 BUT IVORE study Johannes-Boyau Intensi ve Care Med Sep;39(9): Randomised, controlled intervention in sepsis 140pt comparing 70 vs.35ml/kg/hr. Result: no reduction of 28-day mortality. No early improvement in haemodynamic profile or organ function. Why?

28 Adsorption- filters polyacrylonitrile membrane highest adsorptive capacity High cut of filters kda (Septex) Mogera. Intens care med 2003;29: reduced noradrenalin requirements. Risk for loss of plasma proteins and nutrients. Adsorption: Oxiris. Carvetta. Abstract ESICM 2010 Barcelona.!NA,"MAP, " UO,!Lactate,!SOFA. Human studies few, mainly limited to reporting acute parameters. Very limited outcome data.

29 ARDS Possible benefits of CRRT: -Removal of inflammatory mediators -removal of fluid- reduction of extravascular lung water -CRRT associated hypothermia may help reduce C02 production -Addition of CO2 removal device

30 Extra corporeal C02 removal Membrane gas exchange device in the veno-venous circulation of CRRT for the purpose of CO2 elimination and ph compensation. Device names: PALP, MAQUET; ILA-active, NOVALUNG; Hemolung, Alung Novalung added to Prismaflex with or without CRRT High blood flows required (> 300ml/min) excludes/ svårt med citrate. Use: Hypercapnea in moderate ARDS (not for refractory hypoxemia) allow further reduction of Vt/Pplat & limit VILI COPD patients avoid intubation? Evaluation: ESICM Supernova trial, start 2015.

31

32 Dialysability of toxins Influenced by molecular weight, volume of distribution degree of protein binding and water solubility. Ideal drug for dialysis: Non-protein bound, non-lipophillic, low VD (<0,5l/kg) CRRT are less useful if poison is: Large molecules, charged (polar), large VD ( stored in fatty tissue) or extensively bound protein eg. (digoxin).

33 Dialysable drugs/toxins Methanol Ethanol Glycol Metformin Lithium Salicylates Theophylline Carbamazepine Sodium Valproate Non Dialysable Digoxin Tricyclic antidepressants Phenytoin Benzodiazepines Warfarin Macrolides and quinolones phencyclidine, phenothiazines Fluorides Aminoglycozides, metronidazole most cephalosporins and Penicillins

34 Toxin MW (da) Vd (l/kg) Indications for RRT *Ethylene Glycol glycolic acid oxalate nephrotoxic Secondary indications for RRT Lithium Li > 3.5mmol/l Li >2.5mmol/l if symptomatic +! GFR Ethylene Glycol* Severe acidosis AKI or electrolyte imbalance, Alcohol > 50mg/ dl, Non response to ICU rx. Methanol as above as above Salicylates# Salicylates > 80mg/dl Or 50mg/dl if CNS depression +Methanol formic acid #Salicylates 90% protein bound at therapeutic levels.50% of protein bound salicylates removed by haemodialysis. stop dialysis at levels < 10mg/dl. Bayliss G. Hemodialysis International 2010;14: Dialysis in the poisoned patient.

35 Rhabdomyolysis

36 Myoglobin 17 kda oxygen carrying haem protein. When >100g skeletal muscle damaged, myoglobin exceeds protein binding capacity and precipitates. Mechanisms of AKI : Intravascular volume depletion, fluid sequestration to injured muscle, intratubular heme-pigment cast formation, oxidative stress due to inflam mediators & innate immune activation Treatment: Aggressive volume with isotonic crystalloids. Urine alkalinisation to improve solubility & excretion of intratubular casts & attenuate release of free iron from myoglobin.

37 Dialysis? CRRT is effective for treatment of complications i.e. hyperkalaemia & acidosis. Myoglobin is dialyzable, but we don't know if: 1. S Myoglobin is reduced more effectively with RRT than without? Wakabayash Intensive Care Med1994;20(2): blood myoglobin rapidly fell independent of renal function or therapeutic manipulation..indicating that extra renal factors play a major role in disposing circulating myoglobin. Ling. Injury, Int J care injured 43 (2012) Myoglobin has a low sieving coefficient which decreases rapidly over first 12hrs of RRT (adsorption to hemofilter). 2. Outcome is improved? No outcome studies.

38 Continuous renal replacement therapy (CRRT) for rhabdomyolysis Xiaoxi Zeng 1, Ling Zhang 1, Taixiang Wu 2, Ping Fu 1,* Cochrane Kidney and Transplant Group 15 JUN 2014 There was insufficient evidence to discern any likely benefits of CRRT over conventional therapy for people with rhabdomyolysis and prevention of rhabdomyolysisinduced AKI.

39 Tumour lysis syndrome Metabolic disturbance after chemotherapy due to rapid breakdown of neoplastic cells 1.5% children and 5% adults require dialysis during induction therapy. RRT Indications potentially rapid potassium release and accumulation, particularly if urine output is low Severe oliguria or anuria Persistent hyperkalemia Hyperphosphatemia-induced symptomatic hypocalcemia A calcium-phosphate product 70 mg2/dl2

40 Conclusions Consider the broader clinical context, the presence of conditions that can be modified with RRT, and trends of laboratory tests rather than single BUN and creatinine thresholds alone when making the decision to start RRT. Uraemia ( which value?) Acidosis (ph 7,15?) Oligouria (<400ml/24hrs) Volume overload Sepsis Poisons? Rhabdomyolyis, (myoglobin can removed but no evidence of improves outcome)?

41 Fall S: 70 yr old man. ARDS (unknown cause) after CABG + MR B: Previously healthy (HT), creatinine 90 (baseline) A: NIV 5 days, treatment of failure, simdax, furix, sudden deterioration, C: ST 100/min, Norad 0,28 ug/kg/min. lak 1.5, Hb 96 R: Intubated. PC Hypercapnea PCO2 10, ph 7,1 Pa02 9 (Fio2 0,7) Bilateral ground glass appearance, CT chest, Signs of pulmonary odema N: Creatinine 200, urea 19, Cystatin C 2,2, diuresis /ml/day Cumulative fluid balance -5l since admission but today + 2.5L Coag: INR 3,5 (warfarin) Infection: Low Pct, CRP 200, all cultures negative

42 Is there any indication for CRRT? Would you start CRRT? If so choice of filter? Choice of anticoagulant?