Acute Renal Failure and the Effects of Anaesthesia on Renal Function

Question 1

Suggest a definition for acute renal failure

Answer 1

Acute renal failure is a sudden (within 1 - 7 days) and persistent (>24 hours) decrease in renal function leading to the accumulation of nitrogenous and non-nitrogenous waste products.

Question 2

What prompted the establishment of the RIFLE criteria in 2004

Answer 2

There are more than 30 definitions of acute renal failure. Most relate to absolute or relative changes in serum creatinine.

A lack of consensus in definitions has made comparisons of studies in the literature difficult

Question 3

What does RIFLE stand for

Answer 3

Risk
Injury
Failure
Loss
ESKD

Question 4

What is the RIFLE criteria used for

Answer 4

The RIFLE criteria allow for AKI to be objectively and uniformly defined.

Question 5

Describe the RIFLE criteria

Answer 5

Risk:
SCr x 1.5 or GFR >25 % | UO < 0.5ml/kg/hr x 6h

Injury:
SCr x 2 or GFR >50% | UO < 0.5ml/kg/hr x 12h

Failure:
SCr ≥ 354 umol/L or acute rise ≥ 44umol/L or
SCr x 3/GFR >75% | UO< 0.3 ml/kg/hr x 24h / anuria x 12h

Loss:
ARF > 1/12

ESKD
ARF > 3/12

Question 6

Classify Acute Kidney Injury

Answer 6

Classifying changes have to occur within 48 hours

Stage 1
Baseline SCr x 1.5 to 2.0
UO < 0.5 ml/kg/hr x 6 - 12 h

Stage 2
Baseline SCr x 2 - 3
UO < 0.5 ml/kg/hr x > 12 h

Stage 3
Baseline SCr > x 3 or SCr ≥ 354 umol/L with acute Increase of 44 umol/L
UO < 0.3 ml/kg/hr x 24 hours or anuria x 12 hours

Question 7

What is the Cockcroft Gault equation

Answer 7

Estimated GFR = 1.22(140-age) x weight (kg) x SCr

x 0.85 if female

Question 8

How is body surface area calculated from weight and height

Answer 8

Mosteller formula

= √[(cm x kg)/3600]
= xxx m^2

Question 9

What is the normal range for GFR adjusted for body surface area?

Answer 9

100 - 130 ml/min/1.73m^2

Question 10

What is urea?

Answer 10

by-product of protein metabolism

Question 11

What are the effects of urea retention

Answer 11

1. Increased oxidative stress
2. Altered regulation of K+ and H20 regulation (altered Na/K/Cl co-transport function)
3. Altered immune function

Question 12

Why can’t urea be used to calculate GFR

Answer 12

Urea rises as GFR falls but the relationship is NON-LINEAR

Question 13

What increases the rate of urea production

Answer 13

1. High protein intake
2. ‘Protein meal’ from an upper GI bleed
3. Critical illness (sepsis/burns/trauma)
4. Drug therapy: tetracyclines and corticosteroids

Question 14

What reduces plasma urea levels (even if GFR is reduced)

Answer 14

1. Chronic liver disease

2. Low protein intake

Question 15

Why is there is disproportionate increase in urea in states of acute volume depletion

Answer 15

Compensatory mechanisms (RAAS) lead to enhanced reabsorption of Na and H2O in the PCT. Re-absorption of urea in the PCT is simultaneously enhanced leading to a disproportionate increase in urea versus creatinine

Question 16

What % of urea is passively reabsorbed in the PCT

Answer 16

40 - 50% of urea filtered

Question 17

What is creatine phosphate

Answer 17

Creatine phosphate is a rapidly mobilizable potential store for high energy phosphate bonds in myosites and neurones.

Question 18

What is creatinine, how is it produced and excreted

Answer 18

Creatinine is an amino acid product of creatine phosphate metabolism.

Released into plasma at a relatively constant rate (c.f. urea)
Filtered freely at glomerulus
Neither reabsorbed nor metabolized by the kidney

Question 19

What % of kidney function should be lost before a rise in serum creatinine is observed

Answer 19

> 50%

Question 20

Why does serum creatinine not rise until approximately 50% of kidney function is lost

Answer 20

10 - 40% of creatinine clearance occurs by tubular secretion. As GFR falls secretion may increase preventing an immediate rise in creatinine subsequent to declining GFR

Question 21

Which drugs impair creatinine secretion causing a transient reversible increase in serum creatinine

Answer 21

Trimethoprim

Cimetidine

Question 22

What factors affect creatinine production

Answer 22

Age (less)
Sex (male more)
Dietary intake (more protein more Cr)
Muscle mass (more mass more Cr)
Disease (rhabdomyolysis)

Question 23

Does serum creatinine depict real time changes in GFR with acute reductions in kidney function

Answer 23

NO - Time is required for accumulation to occur prior to detection of abnormal raised levels - this results in a delayed diagnosis of AKI

Question 24

What are the limitations of urine output as a gauge of kidney function

Answer 24

UO lacks sensitivity and specificity for acute kidney injury. Even patients with severe AKI, characterized by a marked raise in SCr, can maintain normal or raised urine output.

Question 25

How should urine output be used clinically to assess kidney function

Answer 25

Trends of urine output over a period of time are useful clinical barometer of GFR

Question 26

What limits the use of UO as a gauge of kidney function during the intra-operative period?

Answer 26

Increased ADH release in response to surgical stress reduces intra-operative urine output. However, if the UO reduction persists, alternate explanations must be sought

Question 27

Case: An otherwise fit 57-year-old Caucasian male underwent a difficult elective open abdominal aortic aneurysm repair 12 hours ago with a prolonged aortic cross clamp time. He has passed no urine postoperatively, his preoperative creatinine was 122 μmol/L and is 136 μmol/L postoperatively. Select one option from the answers below. ``` Possible answers: A. At risk B. Renal injury C. Renal failure D. Unable to classify ```

Answer 27

C - Renal Failure His urine output places him in the failure group. The change in creatinine level is below that required to suggest failure, but this is due to the short time interval resulting in a lack of significant accumulation.

Question 28

Classify the causes of pre-renal failure

Answer 28

1. Reduced absolute circulating volume - haemorrhage - dehydration - redistribution (third space fluid loss) 2. Reduced effective circulating volume - Heart failure - Decompensated liver cirrhosis 3. Arterial occlusion or stenosis of renal artery or raised intra-abdominal pressure 4. Reduced CO - Myocardial ischaemia - Tamponade 5. Drugs - ACEi - NSAIDS

Question 29

Describe the different biochemical urinary measurements in pre-renal and renal failure

Answer 29

Urinary Na (mmol/L) - Pre-renal: <20 - Renal: >40 FeNa - Pre-renal: <1% - Renal: >1% Urinary Osmolarity (mosm/L) - Pre-renal: >500 - Renal: <350 Urine/plasma urea - Pre-renal: >8 - Renal: < 3 Urine microscopy - Pre-renal: Hylaine or fine granular casts - Renal: Coarse granular muddy brown and mixed cellular casts (- vasculitis/GN - dysmorphic RBCs or RBC casts) Specific gravity - Pre-renal: High - 1,020 - Renal: Fixed 1,010 - 1,020

Question 30

Classify the causes of intra-renal failure

Answer 30

Endogenous toxins - Rhabdomyolysis (myoglobinuria) - Haemolysis (haemoglobinuria) - Myeloma - Intratubular crystals (uric acid/oxalate) Exogenous toxins - Aminoglycosides - Radiocontrast - Cisplatin Vascular - Malignant hypertension - Vasculitis - Acute Glomerulonephritis Ischaemia/Sepsis Drugs - Antibiotics (penicillins, cephalosporins, quinolones) - NSAIDS - Diuretics (thiazides, furosemide) - Allopurinol - Phenytoin - Rifampicin

Question 31

How do NSAIDS cause pre-renal failure

Answer 31

Prostaglandins (PGs) with best-defined renal functions are PGE2 and prostacyclin (PGI2). These vasodilatory PGs increase renal blood flow and glomerular filtration rate under conditions associated with decreased actual or effective circulating volume, resulting in greater tubular flow and secretion of potassium. NSAIDS inhibit COX enzyme which inhibits the production of PGE2 and PGI2 locally in the kidney leading to a loss of the protective vasodilatory effects

Question 32

Describe the problems encountered with ARF

Answer 32

1. Volume overload and pulmonary oedema 2. Electrolyte imbalance (K+) 3. Metabolic acidosis 4. Uraemia - e.g. pericarditis 5. Altered drug handling - Reduced excretion and potential accumulation - Acidosis/Uraemia displace protein bound drugs

Question 33

What are the ECG findings in hyperkalaemia

Answer 33

Flat P Widened QRS Peaked T Progressing toward sine wave pattern Non-specific repolarization abnormalities Bradycardia AV block Cardiac arrest: PEA/Asystole/VF

Question 34

What is the treatment of severe hyperkalaemia?

Answer 34

1. OMIGABCDE 2. Discontinue cause if possible 3. ECG findings: Give calcium chloride 10% 10ml over 10 min (Or calcium gluconate10 ml - repeated x3 if required) 4. K+ shift: 50ml 50% dex with 10U actrapid then 10% Dex follow up infusion monitor hgt 5. Salbutamol 10 -20 mg neb 6. Fluid overloaded: NaHCO3- 8.4 % 50 - 100 mls Fluid depleted - start with isotonic NaHCO# after calculating HCO3- deficit 7. Increase K+ excretion (Kayexelate vs furosemide)

Question 35

What are indications for early Renal Replacement Therapy

Answer 35

1. Hyperkalaemia with ECG changes 2. Severe pulmonary edema 3. Uraemic pericarditis resulting in obstructive shock

Question 36

What are the relative indications for RRT

Answer 36

``` Oliguria - UO < 200 ml in 12 h Anuria - UO < 50 ml in 12 h Hyperkalaemia > 6.5 mmol/L Severe acidaemia pH < 7.0 Azotaemia: Urea > 30 mmol/L Uraemic complications: - encephalopathy - pericarditis - neuropathy Hyperthermia Drug overdose with dialysable toxin ```

Question 37

What should be considered prior to taking a patient who has recently had RRT to theatre

Answer 37

1. ? anticoagulant used on filter and platelet count 2. ? volume status (fluid removed during RRT) 3. ? vascular access (fistulae C/I unless life threatening issue) 4. Ineffective RRT possible: check and Rx UE and CMP before anaesthesia

Question 38

What different anticoagulants can be used on the haemodialysis filter

Answer 38

1. Heparin - Most common agent used - T1/2 heparin is 90 minutes - check aPTT - check platelets (consumed on filter) - Caution: neuraxial blockade 2. None - If systemically anticoagulated - OR if at risk of bleeding - Can reduce filter time as clot more likely and full dose RRT may not be achieved 3. Prostacyclin (epoprostenol) - Direct inhibition of platelet aggregation - T1/2 = 2 minutes - Used if heparin contra-indicated or in combination with heparin in a prothrombotic patient 4. Citrate - Chelates calcium and prevents clotting - Calcium has to be replaced in the blood returning to the patient - Check Ca levels

Question 39

Describe pharmacalogical alterations in patients at risk of or with ARF

Answer 39

1. Induction agents - limit dose to avoid hypotension 2. NMB - SUX - consider possible K + rise (use Roc for RSI) - Atracurium ideal (Hofmann degradation) - Vecuronium and mivacurium ok (minimal renal excretion) 3. Volatile agents: Avoid Sevoflurane 4. Analgaesia: - Avoid large repeated doses morphine/pethidine. - Avoid NSAIDS 5. Antibiotic prophylxis - Dose adjustment - Avoid aminoglycosides 6. Anticoagulants - LMWH - needs dose adjustment

Question 40

Why should sevoflurane be avoided in ultra-low flow circuits?

Answer 40

Undergoes temperature-dependent degradation by baralyme and soda lime --> formal a special haloalkene = compound A. Compound A is metabolized to nephrotoxins which can result in kidney damage (theoretical risk) No demonstrated increase in risk of ARF with sevoflurane in millions of anaesthetics worldwide

Question 41

Describe the SNS response to hypovolaemia and the local role of prostaglandins in the kidney

Answer 41

SNS --> VC autoregulation to maintain filtration pressure PGI2 is released locally to cause local vasodilatation and partially oppose the VC NSAIDS --> unopposed vasoconstriction and may cause further deterioration in renal function

Question 42

Why are morphine and pethidine less suitable in patients with renal failure. Which opioids are preferred in ARF

Answer 42

Morphine-6-glucoronide (active metabolite or morphine) --> excessive prolonged opioid effects/side effects Norpethidine (metabolite of pethidine) --> pro-convulsant --> accumulates in renal failure Fentanyl and alfentanil --> use as normal but remember that they have context specific half life if used as infusions Fentanyl PCA instead of morphine PCA

Question 43

What happens to the renal blood flow autoregulatory range in hypertension

Answer 43

it shifts to the right and is narrower meaning that at MAP that achieve adequate renal blood flow in normotensive patients may generate insufficient renal blood flow in hypertensive patients as the autoregulatory range has narrowed and shifted (Draw Graph relative renal blood flow to MAP)

Question 44

What should be considered with regard to neuraxial blockade in patients with ARF

Answer 44

Consider that sympathetic blockade may extend above renal sympathetic fibres --> loss of normal autoregulatory mechanisms to maintain renal perfusion Caution is also required with the timing of the pre- and postoperative dialysis due to the potential use of anticoagulation