What Im not going to tell you Acute renal failure/acute kidney - PDF document

5/31/2013 What I’m not going to tell you • Acute renal failure/acute kidney injury is associated with an increased risk of death Acute Kidney Injury • Despite many efforts, we have no therapies to treat or prevent acute kidney injury May 2013 Kathleen D. Liu, MD, PhD What I am going to tell you • New KDIGO guidelines on AKI (broad overview) • Impact of fluid selection on AKI • Dialysis may have adverse consequences for patients due to antibiotic underdosing 1

5/31/2013 Grading System for Guidelines Grading System for Guidelines Grade Meaning Grade Implications Patients Clinicians Policy Strength of recommendation Level 1 Most people in your situation Most patients should receive The recommendation can be Level 1 Strong recommendation - “we recommend” “we recommend” would want the recommended the recommended course of evaluated as a candidate for Level 2 Weak recommendation – “we suggest” course of action and only a small action developing a policy or a proportion would not performance measure Not graded Insufficient evidence for systematic evidence review Strength of evidence Level 2 The majority of people in your Different choices will be The recommendation is likely “we suggest” situation would want the appropriate for different to require substantial debate A High recommended course of action, patients. Each patient needs and involvement of stake- but many would not help to arrive at a management holders before policy can be B Moderate decision consistent with his or determined her values and preferences C Low D Very low Comparison of RIFLE, AKIN and KDIGO Guideline Scores Definitions and Staging of AKI RIFLE definition Increase in SCr by ≥1.5 times baseline within 7 days 7 staging R: Increase in SCr by 1.5 - <2.0 times baseline I: Increase in SCr by 2.0 - <3.0 times baseline Not Graded Not Graded F: Increase in SCr by ≥3.0 times baseline 29.9% 26 1A AKIN definition Increase in SCr by 0.3 mg/dL or ≥1.5 times baseline within 48 1B 20 Level 2 hours 1C 44.8% staging 1: Increase in SCr by ≥0.3 mg/dL or ≥1.5 - <2.0 times 1D baseline 2A 2: Increase in SCr by ≥2.0 - <3.0 times baseline 3: Increase in SCr by ≥3.0 times baseline 2B KDIGO definition Increase in SCr by 0.3 mg/dL within 48 hours; or 2C 9 10 Increase in SCr by ≥1.5 times baseline within 7 days 2D staging 1: Increase in SCr by ≥0.3 mg/dL or ≥1.5 - <2.0 times 2 Level 1 10 3 25.3% baseline 2: Increase in SCr by ≥2.0 - <3.0 times baseline 3: Increase in SCr by ≥3.0 times baseline 2

5/31/2013 Editorial comments Stage-based Management of AKI • Did we really need to revise the definition…again? • Distracting to combine two different timeframes (48h and 7 days) • Unclear how these cutpoints were derived • Urine criteria remain largely unvalidated • Unclear how to use this definition in clinical practice (what do I do about it?) Editorial comments Prevention of AKI: Section 3 • Not sure that these are all truly actionable: 3.1: Management of shock • Seem to rely too much on staging: 3.3: Nutrition – “ C onsider RRT/consider ICU admission” for Stage 2 3.4-3.6: Diuretics and pharmacotherapy AKI? 3.7: Theophylline for perinatal asphyxia • If Cr goes from 0.6->1.2, is RRT or ICU needed? (maybe, but probably not) 3.8: Aminoglycosides and amphotericin – Similarly, don’t need to change drug dosing until 3.9: Off pump CABG you have Stage 2 AKI? • If Cr goes from 2->3.9, probably need to redose medications? 3

5/31/2013 Contrast Nephropathy: Section 4 Dialysis: Section 5 4.3.2: We recommend using either iso-osmolar or low- 5.3 Anticoagulation for all? osmolar iodinated contrast media, rather than high- 5.3.1.1: We recommend using anticoagulation during RRT in osmolar iodinated contrast media in patients at AKI if a patient does not have an increased bleeding increased risk ( 1B ) risk or impaired coagulation and is not already 4.4.1: We recommend i.v. volume expansion with either receiving systemic anticoagulation ( 1B ) isotonic sodium chloride or sodium bicarbonate 5.3.2.1: For anticoagulation in intermittent RRT, we solutions, rather than no i.v. volume expansion in recommend using either unfractionated or low- patients at increased risk for CI-AKI ( 1A ) molecular heparin rather than other anti-coagulants ( 1C ) 4.4.2: We recommend not using oral fluids alone in 5.3.2.2: For anticoagulation in CRRT, we suggest using regional patients at increased risk of CI-AKI ( 1C ) citrate anticoagulation rather than heparin in patients who do not have contraindications for citrate ( 2B ) Vascular access for renal replacement Editorial comment therapy in AKI • Low molecular weight heparin – clearance is 5.4.1: We suggest initiating RRT in patients with AKI via an uncuffed nontunneled dialysis catheter rather than a variable in renal failure, morbidly obese tunneled catheter ( 2D ) • Citrate guidelines – impractical in US? 5.4.2: When choosing a vein for insertion of a dialysis catheter – All IV citrate solutions in the US are approved for in patients with AKI, consider these preferences ( not use in blood banking graded ) • First choice: right jugular vein – Consequently these solutions are very hypertonic • Second choice: femoral vein and citrate protocols may be fraught with • Third choice: left jugular vein • Last choice: subclavian vein with preference for the complications…. dominant side 4

5/31/2013 Editorial comment Data for site selection • Guidelines fail to consider impact of CKD on outcomes from AKI Pre-admission GFR Inpatient mortality Recovery of renal (mL/min/1.73 m2) (%) function among survivors > 90 53% 100% ≥ 45 41% 84% 30-44 35% 58% 15-29 28% 37% Schiffl, NDT 2006; Hsu CJASN 2009; Lo KI 2009 Parienti et al, CCM 2010 Vascular access for renal replacement Modality of renal replacement therapy in AKI therapy in AKI 5.4.3: We recommend using ultrasound guidance for dialysis 5.6.1: Use continuous and intermittent RRT as complementary catheter insertion ( 1A ) therapies in AKI patients ( not graded ) 5.4.4: We recommend obtaining a chest radiograph promptly 5.6.2: We suggest using CRRT, rather than standard intermittent after placement and before first use of an internal jugular RRT, for hemodynamically unstable patients ( 2B ) or subclavian dialysis catheter ( 1B ) 5.6.3: We suggest using CRRT, rather than intermittent RRT, for 5.4.5: We suggest not using topical antibiotics over the skin AKI patients with acute brain injury or other causes of insertion site of a nontunneled dialysis catheter in ICU increased intracranial pressure or generalized brain patients with AKI requiring RRT ( 2C ) edema ( 2B ) 5.4.6: We suggest not using antibiotic locks for prevention of [Some commentary in guidelines themselves on PIRRT/SLED] catheter-related infections of nontunneled dialysis catheters in AKI requiring RRT ( 2C ) 5

5/31/2013 Hydroxyethyl Starch AKI and fluid management • Prior studies have suggested increased rates of • Volume overload and outcome ascertainment AKI with HES • Hydroxyethyl starch • Chloride-rich fluids • CHEST: 7000 patients (Australia/NZ) randomized to receive 130/0.4 HES or saline • Follow up to 90 days VISEP, NEJM 2008 Myburgh et al, NEJM 2012 CHEST Study CHEST Study Myburgh et al, NEJM 2012 6

5/31/2013 CHEST Study CHEST Study CHEST Study CHEST Study 7

5/31/2013 CHEST: Conclusions Chloride rich solutions and AKI • Largest study of HES in critically ill patients • Rationale: Hyperchloremia can lead to renal vasoconstriction with associated reductions in • No benefit and possible harm with HES GFR • Caveats: • Pre/post study: – Serum Cr, urine output that are used to define AKI may be affected by type of resuscitation 0.9% NS Hartmann solution fluid/changes in volume of distribution 4% gelatin Plasmalyte-148 – RRT should be less affected (though subjective); 4% albumin 20% salt-poor albumin blinding helps Yunos et al, JAMA 2012 Chloride rich solutions and AKI Chloride rich solutions and AKI 8

5/31/2013 Chloride rich solutions and AKI Chloride rich solutions and AKI Chloride rich solutions: Limitations Conclusions • Multiple interventions: unclear which • Results are intriguing and warrant component of intervention was associated repeating/study in other contexts with change in AKI • With some exceptions, use balanced salt • Other temporal changes in care? solutions rather than isotonic saline • Some differences in acquisition cost, but these should not drive fluid selection 9

5/31/2013 Issues with drug dosing for RRT Classification of Antibacterial Activity • Specifics of RRT are not standardized Time-Dependent Concentration-Dependent – Modality: IHD, CRRT, SLED/PIRRT Beta-lactams Aminoglycosides – Dose: Blood flow/dialysate flow rate, treatment Fluoroquinolones Clindamycin time [other features like filter type are fairly Daptomycin Macrolides standard now] Linezolid Metronidazole • Critically ill patients may have large Doxycycline Telithromycin differences in volume of distribution, protein Tigecycline Vancomycin binding, endogenous hepatic/renal clearance Failure to achieve PK/PD targets is Pharmacodynamic Interactions common with CRRT Concentration Peak/MIC Dependency Concentration Time AUC/MIC Dependency Time above MIC Sub-MIC PAE MIC Time Seyler, Crit Care, 2011 10