Acute Kidney Injury in ICU Dr. Firouzeh Moeinzadeh Nephrologist 2/30/1395

Purposes Definition of AKI Etiology of AKI in ICU setting Renal replace therapy in ICU Fluid or diuretics? 2/30/1395

AKI is not a single disease but rather a syndrome comprising multiple clinical conditions 2/30/1395

Depending on the definition, acute renal failure was said to affect anywhere from 1 to 25% of intensive care unit (ICU) patients and to carry a mortality rate from 15 to 60%. 2/30/1395

Patients, especially patients in the ICU, are dying of AKI and not just simply with AKI. 2/30/1395

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RIFLE classification was useful for predicting Recovery of renal function: P≤0.001 Requirement for renal replacement therapy: P≤0.001 Length of hospital stay for survivors: P≤0.001 In-hospital mortality: P=0.035 2/30/1395

Survival appears to be affected for at least 1 year and maybe longer. It is the interaction between susceptibility (i.e., features intrinsic to the patient) and exposure (i.e., the causative factor or factors). 2/30/1395

Urinary tract obstruction Exposures: Myonecrosis Heart failure Sepsis Nephrotoxins Ischemia Urinary tract obstruction Major surgery Liver disease 2/30/1395

SEPSIS induced AKI Several studies have reported that sepsis induced AKI is associated with short- and long-term risk of death. The development of sepsis appears to be common in patients with AKI and is associated with high mortality and increased hospital duration. 2/30/1395

Multiple common settings: sepsis, cardiac surgery, radio contrast…… is common!! 2/30/1395

Recovery of renal function is also a problem, with many patients failing to recover renal function: patients with AKI who required renal replacement therapy that 33% of the survivors were still on renal replacement therapy after 12 months. 2/30/1395

less severe AKI may be associated with important long-term outcomes including progression of CKD and cardiovascular disease 2/30/1395

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AKI and the (innate) immune system Increased myocardial transcription of tumor necrosis factor-a and interleukin (IL)-1. Blockade of tumor necrosis factor-a inhibited apoptosis. Patients with septic AKI have impaired leukocyte rolling when compared with septic patients without AKI. 2/30/1395

Treatment of AKI Intermittent hemodialysis (IHD), Treatment of acute kidney injury (AKI) is principally supportive -- renal replacement therapy (RRT) indicated in patients with severe kidney injury. Goal: optimization of fluid & electrolyte balance Multiple modalities of RRT : Intermittent hemodialysis (IHD), continuous renal replacement therapies (CRRTs) hybrid therapies, ie sustained low-efficiency dialysis (SLED) 2/30/1395

Timing of initiation of RRT Earlier initiation of RRT in critically ill patients with AKI may have a beneficial impact on survival and outcomes but data is insufficient Many recommend initiation of RRT prior to the development of advanced uremic symptoms, or when the BUN reaches 80 - 100 mg/dL No known threshold of fluid overload for initiating RRT 2/30/1395

Discontinuation of RRT Until “evidence of recovery of kidney function” Improved urine output in oliguria Decreasing creatinine Creatinine clearance minimum 12 mL/min, some say 20 mL/min 2/30/1395

RRT in sepsis/MODS RRT has been proposed as a “Extracorporeal blood purification therapy (EBPT)” as adjuvant therapy for sepsis/MODS for removal of harmful inflammatory mediators or endotoxemia Some support from animal models and small clinical studies Eg cytokines can be demonstrated in dialysis effluent Miller's Anesthesia, 7th ed. 2009 2/30/1395 Foot. Current Anaesthesia and Critical Care 2005; 16:321-329

RRT in sepsis/MODS Overall, no good data showing improved outcomes Insufficient evidence to support a role for RRT as adjuvant therapy for septic shock unless severe acute renal failure is present. 2/30/1395

Conclusions AKI in the ICU is common and associated with high mortality The best time to initiate and stop RRT is controversial No good data that CRRT is better than IRRT in the ICU, except for a few specific situations Consider CRRT if severely unstable pts, severe volume overload, combined renal/hepatic failure IRRT best if bleeding risk or acute hyperkalemia/poisoning SLED is the most flexible 2/30/1395

Conclusions More intense RRT dosing in the ICU does not improve outcome Insufficient evidence to support a role for RRT as adjuvant therapy for septic shock unless severe acute renal failure is present Ultrafiltration is effective for fluid removal in CHF 2/30/1395

Specific considerations in ICU patients with AKI 2/30/1395

Oliguria and AKI in ICU Very common. Oliguria is short-lived, the typical response is observation (but not always). Is sustained, two responses are typically applied Fill (fluid administration) hoping that urine will “spill” Squeeze (increase BP with vasoactive drugs) and diurese (start and sustain diuresis with loop diuretic) 2/30/1395

Fill and Spill is dangerous and futile In the vast majority of ICU patients there is no “fluid depletion” More fluid= No difference to renal blood flow 2/30/1395

More fluid =Minor short-lived changes in urine output More fluid =Increased risk of dangerous fluid overload Yet “fill & spill” is very common 2/30/1395

After fill and spill (into the lungs!) 2/30/1395

Why we need to squeeze Almost all ICU patients are fluid replete Almost all are relatively hypotensive The typical MAP in a 60 year old man is >100 mmHg !! 2/30/1395

Renal blood flow is pressure dependent at low MAP Restoring blood pressure closer to normal may improve renal blood flow and diuresis 2/30/1395

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Why we also need to diurese Sustained oliguria leads to fluid overload due to obligatory fluid intake in ICU Fluid, acid-base, potassium management is much easier if urine output is maintained Loop diuretics have useful effects on renal hemodynamics 2/30/1395

Possible beneficial effects of loop diuretics Renal Vasodilatation (Direct vasodilatation, Inhibition of renal prostaglandin dehydrogenase; Blockade of TGF-induced vasoconstriction; Blockade of obstruction effect. Increased tubular flow (Decreased tubular obstruction by casts; Less back-leak; Decreased back pressure with effect on GFR) 2/30/1395

Oliguria/AKI: A Real ICU doctor’s approach Restore MAP with noradrenaline (norepinephrine) Make sure CO is adequate All simultaneous and rapid (minutes) 2/30/1395

Approach….. Administer furosemide infusion Maintain diuresis at between 1-2 ml/kg/hr Administer potassium and magnesium as needed 2/30/1395

The Physiological Folly of (excessive) Fluid Filling Fluids are bad after surgery Fluids are bad in ARDS They are physiologically futile in oliguria After the first couple of hours, they are physiologically irrational in most ICU patients 2/30/1395

In critically ill patients and in patients with AKI, fluid accumulation has been shown to worsen prognosis. A 10% fluid accumulation was associated with adverse outcomes in clinical settings. 2/30/1395

Mortality was lower when fluid overload was corrected by dialysis. The duration of fluid overload while remaining on dialysis was similarly associated with increased mortality, suggesting a cumulative effect of fluid overload on mortality. Mortality was lower when fluid overload was corrected by dialysis. 2/30/1395

Cumulative fluid overload may also be associated with a decreased likelihood of renal recovery. 2/30/1395

Conclusions Fluids can have a high physiological price Fluids do not correct vasodilatation Fluids do not increase renal O2 delivery They do not increase perfusion pressure You can get rid of vasopressor effects in minutes but getting fluid out is not that easy 2/30/1395

Are you agree: fluids kill !! Squeeze and diurese !! 2/30/1395

Thanks for your attention 2/30/1395