How Best To Prevent & Manage Acute Renal- Final

How Best to Prevent & Manage Acute Renal Failure ? Dr. T.R.Chandrashekar Director Critical Care, K.R. Hospital Bangalore

Some facts about ARF • • • •

Incidence=1-25%. Mortality =28-90% High Attributable risk 35 different definitions have been used in the literature, creating confusion and making comparisons among the studies difficult. • This situation has impaired the study of ARF as well as the development of possible treatments. • Recent data indicates that a small change in SC influences outcome.(>0.3 increase in SC ). • A change from 1.5 mg/ml—1.8mg/dl is significant

Definition of ARF • Acute renal failure (ARF) is defined as an abrupt and sustained decline in the glomerular filtration rate (GFR), which leads to accumulation of nitrogenous waste products and uremic toxins. • Few caveats • No consensus on • Assessment of renal function tests • The exact cutoffs values for the diagnosis • The degrees to which the process is “abrupt” or “sustained” are variable.

• The term Acute kidney injury (AKI) has been put forth as the preferred nomenclature to replace acute renal failure with the understanding that the spectrum of AKI is broad and includes different degrees of severity • Because the most powerful tool to improve outcome of AKI is prevention, • The definition should have a high sensitivity, be multifaceted, and allow detection of patients who are at risk to develop kidney injury, as well as those with already established AKI and those with established ARF

Diagnostic criteria for acute kidney injury • An abrupt (within 48 hrs) reduction in kidney function currently defined as • An absolute increase To rule out Foley’s catheter block in serum creatinine of more correlate with clinical picture than or equal To to 0.3 mg/dl or A % increase in Does nor require baseline SC values Correct serum creatinine of volume morestatus than or equal to 50% Look for easily correctable causes orfor reduced UO • A reduction in urine output ( documented oliguria of less than 0.5ml/kg per hour for more than 6 hrs). AKIN march 2007

Acute Dialysis Quality Initiative (ADQI) -RIFLE classification of AKI.

Three stages of increasing severity

Two outcome variables

Modified RIFLE criteria for AKI Classification/Staging system for AKI Stage Serum Creatinine criteria

U.O criteria

1

Increase in SC of >= to 0.3 mg/dl or increase to >= to150-200% from baseline

< 0.5ml/kg/hr for more than 6 hrs

2

Increase to >= to 200%-300 % from baseline

< 0.5ml/kg/hr for more than 12 hrs

3

Increase to >= to 300% from baseline <0.3ml/kg/hr for 24 hrs or Anuria for 12 hrs SC >= 4.0mg/dl with an acute increase of at least 0.5mg/dl

Modified RIFLE criteria for AKI • The staging system proposed is highly sensitive and is based on recent data indicating that a small change in SC influences outcome. • One criteria either SC or UO has to be fulfilled to qualify for staging. • Patients receiving RRT are considered stage -3 irrespective of the stage they are in at the time of RRT.

Causes of AKI CASE-I •

A 20yr old boy with H/o RTA with Hemoperitonium, Thready pulse 150/mt , sweating, restless, BP 70/40mm Hg, UO in last four hrs 30ml

•

PRE-RENAL- Low volume/ Hypoperfusion

CASE-III •

•

•

•

CASE-II A 40 yr old male with small bowel perfusion 2 days back comes with thready pulse 160/mt, cold extremities, restless, BP 80/ 50 mmHg,, Spo2 90% on 4l of O2. with anuria

ATN-ischemic/ toxic

A 40 yr old male with small bowel perfusion 2 days back comes with thready pulse 160/mt, cold extremities, restless, BP 80/ 50 mmHg, distended of abdomen which is very tense, spo2 90% on 4l of O2. with Anuria Decreased renal perfusion –ACS

CASE-IV •

•

A 70 yr old man with no urine output since 2 days, ultrasound shows BPH with distended bladder hydronephrosis and SC of 2.5 mg/dl

Post- Renal

Causes of AKI

Tubulointerstitial

Glomerular – Glomerularnephritis

Drugs, Myeloma Renal causes

ATN Pre renal causes

Hypoperfusion and toxins

Low volume states NSAIDS,ACEI Renal artery stenosis Post renal causes

Renal stones, ureteric stones Ca Cervix Prostate hypertrophy, tumors Renal papillary necrosis

Etiology of ARF 80

ATN is the cause in more than 90% Sepsis is the leading cause of ATN

70 60 50

Outpatient Inpatient

40 30 20 10 0 Prerenal

Intrarenal

Obstruct

Idiopath

DD of type of AKI • Perform careful history, physical exam and urinalysis (sediment and chemistry) • If a patient has been hospitalized for some time prior to developing ARF, you must prepare a flow sheet of vital signs, weights, I/Os, labs, fluids and medications • Imaging- Ultrasound examination, C.T scan, IVP etc…

Laboratory Findings in Acute Renal Failure Index

BUN/PCr Ratio

Prerenal Azotemia

Oliguric Acute Renal Failure (ATN)

>20:1

10-15:1

Urine sodium (UNa), meq/L Urine osmolality, mosmol/L H2O

<20

>40

>500

<350

Fractional excretion of sodium

<1%

>2%

Response to volume Urinary Sediment

Cr won’t improve much Bland

Cr improves with IVF ATN: muddy brown granular casts, cellular debris, tubular epithelial cells

DD of type of AKI • Let us look at an Ex. 40 year old DM in ketosis due to vomiting • Urea 200, SC 5mg/dl • Ratio BUN/SC=40 • Urine Spot Na=15meq/l • Prerenal

Got a diuretic Prolonged hypoperfusion and ATN

• Let us look at an EX. 40 year old DM in ketosis due to vomiting Urine chemistries • Urea 200, SC 5mg/dl cannot be not relied on•to Ratio rule out BUN/SC=40 active renal injury • Urine Spot Na=50meq/l • Prerenal + ATN

Prerenal azotemia and ischemic tubular necrosis represent a continuum. Azotemia progresses to necrosis when blood flow is sufficiently compromised to result in the death of tubular cells.

Mechanism of ATN Septic shock

Volume depletion

Drugs

Low cardiac output Hypo-perfusion

Medullary hypoxia Endothelial damage

Renal blood flow Cortical vasoconstriction GFR

Back leak

Tubular malfunction

Cell shedding Death Tubular obstruction

Anuria Oliguric Renal failure

Toxins

Non-oliguric renal failure

MECHANISM OF ATN

Prognosis in ATN Full functional recovery 60%

Chronic Renal impairment 30%

End stage renal failure 10%

How best to prevent AKI ? • •

•

No drugs are currently available to enhance or hasten renal recovery once ARF occurs There is now clear evidence that ARF is associated with excess mortality, irrespective of whether the patient requires renal replacement therapy.

Hence prevention is the only powerful tool to improve outcome of AKI.

Window of Opportunity 24 – 48 hrs For Anaesthesiologist This is when and where prediction and prevention strategies must be applied

How best to prevent AKI ? Identification of patients at high risk to develop AKI-Elderly, DM, HT, Sepsis etc.. Non pharmacological Rx • Ensuring adequate hydration (reversing dehydration), • Maintenance of adequate mean arterial pressure, • Minimizing exposure to nephrotoxins

Pharmacological Rx • Loop diuretics • Mannitol • Dopamine & Fenoldopam • Natriuretic Peptides Renal replacement therapy

Hydration • NS or RL • CVP = 8-12 cm H2O, MAP> 65mmHg • Optimal rate of infusion remain unclear and should be individualized.

• Peripheral edema is of cosmetic concern in sepsis • The available experimental data are not supportive of a beneficial effect of additional fluid therapy on renal function, in the context where cardiac output is normal or increased and mean arterial pressure is re-established.

Hydroxyethyl starch (HES) • A recent multicenter German study, the Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis study, indicates that HES administration in patients with severe sepsis may be associated with an increased risk of acute renal failure. •

( 27th International Symposium of Intensive Care and Emergency Medicine, Brussels, March 2006.)

• Effects of hydroxyethyl starch administration on renal function in critically ill patients • The administration of HES had no influence on renal function or the need for RRT in the ICU. Br J Anaesth 2007; 98: 216–24

Maintain renal perfusion pressure • Target MAP >=65 mmHg • Which vasopressors to be used ? • Role of low dose dopamine

Vasopressors • Noradrenaline is the drug of choice in AKI in sepsis • Norepinephrine has been demonstrated to preserve splanchnic blood flow better than dopamine • Optimise fluid before starting vasopressors • Low dose dopamine should not be used for renal protection in severe sepsis

Meta-Analysis: Low-Dose Dopamine Increases Urine Output but Does Not Prevent Renal Dysfunction or Death

• Conclusion: Low-dose dopamine offers transient improvements in renal physiology, but no good evidence shows that it offers important clinical benefits to patients with or at risk for acute renal failure

Ann Intern Med. 2005;142:510-524.

CASE-III • A 40 yr old male with small bowel perfusion 2 days back comes with thready pulse 160/mt, cold extremities, restless, BP 80/ 50 mmHg, distended abdomen which is very tense, Spo2 89% on 6l of O2 with Anuria.

ACS • Oliguria is one of the first visible signs of elevated IAP • “Normal IAP is approximately 5-7 mmHg in critically ill adults.” • “IAH is defined by a sustained or repeated pathological elevation in IAP ≥ 12mmHg.” • “ACS is defined as a sustained IAP > 20mmHg (with or without an APP < 60mmHg) that is associated with new organ dysfunction/ failure.”

Monitoring & Management - ACS Surgical decompression or if the pt is sick put flank drains

Nephrotoxic drug exposure • Minimizing nephrotoxin exposure is an important strategy to prevent ARF in the ICU setting • Aminoglycosides, • Amphotericin,-lipid forms of amphotericin B be used preferentially in patients with renal insufficiency or evidence of renal tubular dysfunction. • Radiocontrast • are the most commonly encountered nephrotoxins in the ICU

Aminoglycoside • Once-daily dosing is postulated to decrease tubular cell toxicity by reducing the fraction of the cumulative dose of drug taken up by proximal tubular cells. • Once-daily aminoglycoside dosing schedules demonstrated that there were no differences in the efficacy of aminoglycosides & there was a trend toward lower nephrotoxicity

Radiocontrast agents • Reduce renal function by altering renal hemodynamics • Exert direct toxic effects on tubular epithelium. • Renal free-radical production increases after contrast agent administration and may in part be responsible for the renal injury. • Lowest volume necessary of nonionic, • Iso-osmolar, contrast medium be used in conjunction with IV isotonic fluids in all high-risk patients.

Radiocontrast agents • NS 1ml/kg/hr/24hrs • N-acetyl cysteine (NAC) 1200mg BD a day before and on the day of contrast administration • Administration of 200mg theophylline 30 min before the procedure in a high risk pt Bicarbonate- Alkalinizing urine should reduce renal medullary damage D5W with 3 amps HCO3; bolus 3.5 mL/kg 1 hour pre-procedure, Then 1mL/kg/hour for 6 hours post-procedure • Insufficient evidence to support the use of prophylactic hemofiltration to prevent contrast nephropathy

Diuretics • Belief – Converts oliguric renal failure into non oliguric which carries lower risk • Clearing tubular debris in ATN • One retrospective study showed diuretic use was associated with significantly increased risk of death or nonrecovery of renal function. Mehta JAMA 2002

• Diuretics are never a treatment for oliguria but are sometimes required for management of volume overload. • Mannitol should not be used to prevent or treat ARF from any cause.

Treatment: Diuretics Diuretics: Effects on outcome (large observational studies) • 4-center, retrospective analysis of patients referred for nephrology consults (1989 - 1995; n = 552) • With adjustments for co-variates and propensity score, diuretic use was associated with: – Significantly increased risk of death or non-recovery of renal function (odds ratio 1.77; 95% CI 1.14 - 2.76) Mehta et al. JAMA. 2002;288:2547-53.

• 52-center, prospective inception cohort of ICU patients (n = 1743) • No differences in mortality, or renal recovery, even after adjustment for the same co-variates and propensity score – Odds ratio 1.22 (p = 0.15)

• However, no benefit associated with diuretics either! Uchino et al. Crit Care Med. 2004;32:1669 –77.

Prevention of AKI summary Strategies that are likely to be effective Isotonic hydration (IV route) Once-daily dosing of aminoglycosides Use of lipid formulations of amphotericin B Use of iso-osmolar nonionic contrast media Strategies of unknown efficacy NAC Theophylline Low-dose recombinant ANP (in cardiac surgical patients) Strategies that are not effective Loop diuretics Dopamine and dopamine receptor agonists ANPs Prophylactic hemofiltration

Indications for RRT in AKI • • • • • • • • •

Volume overload Hyperkalemia Metabolic acidosis Uremia signs or Symptoms Progressive azotemia in the absence of uremia Uremic encephalopathy Uremic neuropathy/myopathy Uremic pericarditis Drug overdose with dialyzable toxin

Goals of RRT • To maintain fluid and electrolyte, acidbase, and solute homeostasis • To prevent further insults to the kidney • To promote healing and renal recovery • To permit other support measures such as nutrition to proceed without limitation.

RRT • IHD=CRRT • Daily dialysis in sepsis improves outcome • Most of the conventional assessment of dose of dialysis –underdosing • IHD- can be done without anticoagulants • More solute removal- severe hyperkalemia • CRRT-in hemodynamically unstable pts • Septic mediators removal ?

Renal Replacement therapy

=

What do you think is the problem ? • 70 yr old gentleman with HT, DM IHD, has BPH posted for TURP, well preserved baseline BP 160/90 mm Hg on ACE-I, insulin, Asprin which was stopped 7 days back • Under epidural • During the procedure has increased bleeding, BP 130/90 mmHg post operatively on Inj Inac 50 mg tid/ 20mics fentanyl tid • Baseline SC 1.6 mg/dl increases to 2.5, next day what went wrong ?

Normotensive Ischemic Acute Renal Failure • Normotensive ischemic acute renal failure may develop in pts with hypertension, chronic kidney disease, and old age, on some drugs like ACE-I, ARB, COX2 inhibitors all of which are associated Do not overlook a drop in systolic blood pressure with narrowing and blunted vasodilatory capacity to the low normal range in patients with of renal vessels increased risk of normotensive AKI • Treated quickly by replacing volume, treating infection, or stopping medications such as NSAIDs, diuretics, and antihypertensive agents, especially ACE inhibitors or angiotensin-receptor blockers. Normotensive Ischemic Acute Renal Failure, NEJM Volume 357(8), 23 August 2007, pp 797-805

Take home thoughts • Even a small rise in SC to the tune 0.3mg/dl can influence the outcome • Prevention is the only powerful tool available for managing AKI • Use standard definitions like AKI and Modified RIFILE classification in all studies. • AKI=ATN

Take home thoughts • Time is important-EGDT Energy failure may be due to primitive hemodynamic inadequacy and/or mitochondrial dysfunction • Prolonged energy failure leads to irreversible mitochondrial dysfunction (necrosis – apoptosis) • Once MMDS starts shock becomes irreversible • Source control, appropriate antibiotics, hemodynamic stabilisation, APC etc…

“Back to basics": Optimise Volume and Defend Pressure. There are no magic bullets just high quality intensive care