How Best To Prevent & Manage Acute Renal failurePresentation Transcript
How Best to Prevent & Manage Acute Renal Failure ? Dr. T.R.Chandrashekar Director Critical Care, K.R. Hospital Bangalore
Some facts about ARF
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.
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 A cute 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 in serum creatinine of more than or equal to 0.3 mg/dl or A % increase in serum creatinine of more than or equal to 50%
A reduction in urine output ( documented oliguria of less than 0.5ml/kg per hour for more than 6 hrs).
AKIN march 2007 To rule out Foley’s catheter block To correlate with clinical picture Does nor require baseline SC values Correct volume status Look for easily correctable causes for reduced UO
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 <0.3ml/kg/hr for 24 hrs or Anuria for 12 hrs Increase to >= to 300% from baseline SC >= 4.0mg/dl with an acute increase of at least 0.5mg/dl 3 < 0.5ml/kg/hr for more than 12 hrs Increase to >= to 200%-300 % from baseline 2 < 0.5ml/kg/hr for more than 6 hrs Increase in SC of >= to 0.3 mg/dl or increase to >= to150-200% from baseline 1 U.O criteria Serum Creatinine criteria Stage
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
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
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
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
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
Pre renal causes Low volume states NSAIDS,ACEI Renal artery stenosis Post renal causes Renal stones, ureteric stones Ca Cervix Prostate hypertrophy, tumors Renal papillary necrosis Renal causes Glomerular –Glomerularnephritis ATN Hypoperfusion and toxins Tubulointerstitial Drugs, Myeloma Causes of AKI
Etiology of ARF ATN is the cause in more than 90% Sepsis is the leading cause of ATN
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
Laboratory Findings in Acute Renal Failure Cr improves with IVF Cr won’t improve much Response to volume ATN: muddy brown granular casts, cellular debris, tubular epithelial cells Bland Urinary Sediment >2% <1% Fractional excretion of sodium <350 >500 Urine osmolality, mosmol/L H 2 O >40 <20 Urine sodium (U Na ), meq/L 10-15:1 >20:1 BUN/P Cr Ratio Oliguric Acute Renal Failure (ATN) Prerenal Azotemia Index
Let us look at an Ex. 40 year old DM in ketosis due to vomiting
Urea 200, SC 5mg/dl
Urine Spot Na=15meq/l
Let us look at an EX. 40 year old DM in ketosis due to vomiting
Urea 200, SC 5mg/dl
Urine Spot Na=50meq/l
Prerenal + ATN
DD of type of AKI Got a diuretic Prolonged hypoperfusion and 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. Urine chemistries cannot be not relied on to rule out active renal injury
Mechanism of ATN Hypo-perfusion GFR Renal blood flow Cortical vasoconstriction Anuria Oliguric Renal failure Septic shock Volume depletion Drugs Low cardiac output Toxins Tubular malfunction Non-oliguric renal failure Cell shedding Death Tubular obstruction Medullary hypoxia Endothelial damage Back leak
MECHANISM OF ATN Prognosis in ATN
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.
24 – 48 hrs For Anaesthesiologist This is when and where prediction and prevention strategies must be applied Window of Opportunity
Identification of patients at high risk to develop AKI-Elderly, DM, HT, Sepsis etc.. Renal replacement therapy
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
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
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
Meta-Analysis: Low-Dose Dopamine Increases Urine Output but Does Not Prevent Renal Dysfunction or Death Ann Intern Med. 2005;142:510-524.
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.
ABDOMINAL COMPARTMENT SYNDROME
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
Amphotericin,- lipid forms of amphotericin B be used preferentially in patients with renal insufficiency or evidence of renal tubular dysfunction.
are the most commonly encountered nephrotoxins in the ICU
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
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.
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
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.
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.
Mehta JAMA 2002
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 Loop diuretics Dopamine and dopamine receptor agonists ANPs Prophylactic hemofiltration Strategies that are not effective NAC Theophylline Low-dose recombinant ANP (in cardiac surgical patients) Strategies of unknown efficacy Isotonic hydration (IV route) Once-daily dosing of aminoglycosides Use of lipid formulations of amphotericin B Use of iso-osmolar nonionic contrast media Strategies that are likely to be effective
Indications for RRT in AKI
Uremia signs or Symptoms
Progressive azotemia in the absence of uremia
Drug overdose with dialyzable toxin
Goals of RRT
To maintain fluid and electrolyte, acid-base, 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.
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
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 with narrowing and blunted vasodilatory capacity of renal vessels
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 Do not overlook a drop in systolic blood pressure to the low normal range in patients with increased risk of normotensive AKI
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.
Take home thoughts
Time is important-EGDT
Energy failure may be due to primitive hemodynamic inade q uacy and/or mitoc h ondrial dysfunction
Prolonged energy failure leads to irreversible mitoc h ondrial d y sfunction (necrosis – apoptosis)