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

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

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5/31/2013 What Im 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

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5/31/2013 1

Acute Kidney Injury

May 2013 Kathleen D. Liu, MD, PhD

What I’m not going to tell you

  • Acute renal failure/acute kidney injury is

associated with an increased risk of death

  • Despite many efforts, we have no therapies to

treat or prevent acute kidney injury

What I am going to tell you

  • New KDIGO guidelines on AKI (broad
  • verview)
  • Impact of fluid selection on AKI
  • Dialysis may have adverse consequences for

patients due to antibiotic underdosing

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SLIDE 2

5/31/2013 2 Grading System for Guidelines

Grade Meaning Strength of recommendation Level 1 Strong recommendation - “we recommend” Level 2 Weak recommendation – “we suggest” Not graded Insufficient evidence for systematic evidence review Strength of evidence A High B Moderate C Low D Very low

Grading System for Guidelines

Grade Implications Patients Clinicians Policy Level 1 “we recommend” Most people in your situation would want the recommended course of action and only a small proportion would not Most patients should receive the recommended course of action The recommendation can be evaluated as a candidate for developing a policy or a performance measure Level 2 “we suggest” The majority of people in your situation would want the recommended course of action, but many would not Different choices will be appropriate for different

  • patients. Each patient needs

help to arrive at a management decision consistent with his or her values and preferences The recommendation is likely to require substantial debate and involvement of stake- holders before policy can be determined

Guideline Scores

26 9 10 3 2 10 20 7 Not Graded 1A 1B 1C 1D 2A 2B 2C 2D Not Graded 29.9% Level 1 25.3% Level 2 44.8%

Comparison of RIFLE, AKIN and KDIGO Definitions and Staging of AKI

RIFLE definition Increase in SCr by ≥1.5 times baseline within 7 days staging R: Increase in SCr by 1.5 - <2.0 times baseline I: Increase in SCr by 2.0 - <3.0 times baseline F: Increase in SCr by ≥3.0 times baseline AKIN definition Increase in SCr by 0.3 mg/dL or ≥1.5 times baseline within 48 hours staging 1: Increase in SCr by ≥0.3 mg/dL or ≥1.5 - <2.0 times baseline 2: Increase in SCr by ≥2.0 - <3.0 times baseline 3: Increase in SCr by ≥3.0 times baseline KDIGO definition Increase in SCr by 0.3 mg/dL within 48 hours; or Increase in SCr by ≥1.5 times baseline within 7 days staging 1: Increase in SCr by ≥0.3 mg/dL or ≥1.5 - <2.0 times baseline 2: Increase in SCr by ≥2.0 - <3.0 times baseline 3: Increase in SCr by ≥3.0 times baseline

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5/31/2013 3

Editorial comments

  • 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?)

Stage-based Management of AKI

Editorial comments

  • Not sure that these are all truly actionable:
  • Seem to rely too much on staging:

– “Consider RRT/consider ICU admission” for Stage 2 AKI?

  • If Cr goes from 0.6->1.2, is RRT or ICU needed? (maybe,

but probably not)

– Similarly, don’t need to change drug dosing until you have Stage 2 AKI?

  • If Cr goes from 2->3.9, probably need to redose

medications?

3.1: Management of shock 3.3: Nutrition 3.4-3.6: Diuretics and pharmacotherapy 3.7: Theophylline for perinatal asphyxia 3.8: Aminoglycosides and amphotericin 3.9: Off pump CABG

Prevention of AKI: Section 3

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5/31/2013 4

4.3.2: We recommend using either iso-osmolar or low-

  • smolar iodinated contrast media, rather than high-
  • smolar iodinated contrast media in patients at

increased risk (1B) 4.4.1: We recommend i.v. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no i.v. volume expansion in patients at increased risk for CI-AKI (1A) 4.4.2: We recommend not using oral fluids alone in patients at increased risk of CI-AKI (1C)

Contrast Nephropathy: Section 4

5.3 Anticoagulation for all?

5.3.1.1: We recommend using anticoagulation during RRT in AKI if a patient does not have an increased bleeding risk or impaired coagulation and is not already receiving systemic anticoagulation (1B) 5.3.2.1: For anticoagulation in intermittent RRT, we recommend using either unfractionated or low- molecular heparin rather than other anti-coagulants (1C) 5.3.2.2: For anticoagulation in CRRT, we suggest using regional citrate anticoagulation rather than heparin in patients who do not have contraindications for citrate (2B)

Dialysis: Section 5 Editorial comment

  • Low molecular weight heparin – clearance is

variable in renal failure, morbidly obese

  • Citrate guidelines – impractical in US?

– All IV citrate solutions in the US are approved for use in blood banking – Consequently these solutions are very hypertonic and citrate protocols may be fraught with complications….

Vascular access for renal replacement therapy in AKI

5.4.1: We suggest initiating RRT in patients with AKI via an uncuffed nontunneled dialysis catheter rather than a tunneled catheter (2D) 5.4.2: When choosing a vein for insertion of a dialysis catheter in patients with AKI, consider these preferences (not graded)

  • First choice:

right jugular vein

  • Second choice: femoral vein
  • Third choice: left jugular vein
  • Last choice:

subclavian vein with preference for the dominant side

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5/31/2013 5

Editorial comment

  • Guidelines fail to consider impact of CKD on
  • utcomes from AKI

Pre-admission GFR

(mL/min/1.73 m2)

Inpatient mortality (%) Recovery of renal 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

Data for site selection

Parienti et al, CCM 2010

Vascular access for renal replacement therapy in AKI

5.4.3: We recommend using ultrasound guidance for dialysis catheter insertion (1A) 5.4.4: We recommend obtaining a chest radiograph promptly after placement and before first use of an internal jugular

  • r subclavian dialysis catheter (1B)

5.4.5: We suggest not using topical antibiotics over the skin insertion site of a nontunneled dialysis catheter in ICU patients with AKI requiring RRT (2C) 5.4.6: We suggest not using antibiotic locks for prevention of catheter-related infections of nontunneled dialysis catheters in AKI requiring RRT (2C)

Modality of renal replacement therapy in AKI

5.6.1: Use continuous and intermittent RRT as complementary therapies in AKI patients (not graded) 5.6.2: We suggest using CRRT, rather than standard intermittent RRT, for hemodynamically unstable patients (2B) 5.6.3: We suggest using CRRT, rather than intermittent RRT, for AKI patients with acute brain injury or other causes of increased intracranial pressure or generalized brain edema (2B) [Some commentary in guidelines themselves on PIRRT/SLED]

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5/31/2013 6

AKI and fluid management

  • Volume overload and outcome ascertainment
  • Hydroxyethyl starch
  • Chloride-rich fluids

Hydroxyethyl Starch

  • Prior studies have suggested increased rates of

AKI with HES

  • 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

Myburgh et al, NEJM 2012

CHEST Study

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5/31/2013 7

CHEST Study CHEST Study CHEST Study CHEST Study

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5/31/2013 8

CHEST: Conclusions

  • Largest study of HES in critically ill patients
  • No benefit and possible harm with HES
  • Caveats:

– Serum Cr, urine output that are used to define AKI may be affected by type of resuscitation fluid/changes in volume of distribution – RRT should be less affected (though subjective); blinding helps

Chloride rich solutions and AKI

  • Rationale: Hyperchloremia can lead to renal

vasoconstriction with associated reductions in GFR

  • Pre/post study:

0.9% NS Hartmann solution 4% gelatin Plasmalyte-148 4% albumin 20% salt-poor albumin

Yunos et al, JAMA 2012

Chloride rich solutions and AKI Chloride rich solutions and AKI

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5/31/2013 9

Chloride rich solutions and AKI Chloride rich solutions and AKI Limitations

  • Multiple interventions: unclear which

component of intervention was associated with change in AKI

  • Other temporal changes in care?

Chloride rich solutions: Conclusions

  • Results are intriguing and warrant

repeating/study in other contexts

  • With some exceptions, use balanced salt

solutions rather than isotonic saline

  • Some differences in acquisition cost, but these

should not drive fluid selection

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5/31/2013 10

Issues with drug dosing for RRT

  • Specifics of RRT are not standardized

– Modality: IHD, CRRT, SLED/PIRRT – Dose: Blood flow/dialysate flow rate, treatment time [other features like filter type are fairly standard now]

  • Critically ill patients may have large

differences in volume of distribution, protein binding, endogenous hepatic/renal clearance

Classification of Antibacterial Activity

Time-Dependent Beta-lactams Clindamycin Macrolides Linezolid Doxycycline Tigecycline Concentration-Dependent Aminoglycosides Fluoroquinolones Daptomycin Metronidazole Telithromycin Vancomycin

MIC

PAE Sub-MIC AUC/MIC Peak/MIC Time above MIC Time Concentration

Pharmacodynamic Interactions

Concentration Dependency Time Dependency

Failure to achieve PK/PD targets is common with CRRT

Seyler, Crit Care, 2011

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5/31/2013 11 Our ability to predict clearance is poor

Bauer et al, CJASN 2012

Drug dosing: Practical suggestions

  • Use therapeutic drug monitoring where

feasible (vancomycin, aminoglycosides)

  • Patients rarely die of antibiotic overdosing,

but they are likely to die of antibiotic underdosing (though there are sequelae to

  • verdosing as well)
  • Guidelines are useful, but recognize

that they are based on limited data

Drug dosing: Practical suggestions

  • IHD: high flux therapy, but short, so

reasonable to dose/redose many drugs after dialysis

  • CRRT: continuous rate of clearance, so

typically dose for clearance of 10-30 cc/min (probably sticking to the high side of this)

  • SLED: depending on duration of therapy and

type of antibiotic, may need to consider different dosing regimens on/off therapy….

Summary

  • New guidelines for AKI detection, prevention

and management (KDIGO)

  • Fluid management in AKI is area of growing

interest

– Fluid overload – Avoidance of HES, chloride containing solutions

  • Drug dosing for RRT is problematic – more

studies needed