Dr Riyas A

Acute Renal failure Patho

physiology & anaesthetic

management

Definition“Acute renal failure (ARF) or Acute kidney injury

(AKI) is characterised by deterioration of renal functions over a period of hours to few days, resulting in failure of the kidneys to excrete nitrogenous waste product and to maintain fluid, electrolytes and acid-base homeostasis”.

Harrison's Manual of Medicine,

Diagnostic Criteria's of ARFIntroduced by Acute Kidney Injury Network (AKIN)1. Rapid time course (≤ 48 hrs)2. Reduction in Kidney functions:

a) Rise in S.Creatinine- Absolute ↑ in S.Creatinine of ≥0.3mg/dl (≥ 26.4 μmol/l) or a percentage ↑ in S.Creatinine of ≥50% (1.5 fold from baseline).

b) Reduction in urine output (documented oliguria of ≤0.5 ml/kg/hr for more than six hrs).

Harrison's Manual of Medicine,

Staging System of Acute Kidney InjuryStage Serum Creatinine criteria Urine output criteria

1 Increase in s.creatinine of ≥0.3 mg/dl (≥26.4 μmol/l) orincrease to ≥150% to 200% (1.5- to 2fold) from baseline

Less than 0.5 ml/kg/hr for more than 6 hours

2 Increase in s.creatinine to more than 200% to 300% (> 2 to 3 fold) from baseline

Less than 0.5 ml/kg/hr for more than 12 hours

3 Increase in s.creatinine to more than 300% (> 3 fold) from baseline (or s.creatinine of ≥4 mg/dl [≥354 μmol/l] with an acute increase of at least 0.5 mg/dl [44 μmol/l])

Less than 0.3 ml/kg/hr for 24 hours or anuriafor 12 hours

classification According to urine flow rates

oliguric

non oliguric

Poly uric renal failure

Major problem inability to maintain dynamic balance b/w dietary intake of essential substance and production of waste products

Etiology and PathophysiologyDivided into three major categories:

1. Prerenal ARF (~55%)- Diseases that cause renal hypoperfusion, resulting in ↓ function without frank parenchymal damage,

2. Renal or Intrinsic ARF (~40%)- Diseases that directly involve the renal parenchyma,

3. Postrenal ARF (~5%)- Diseases associated with urinary tract obstruction.

Prerenal Azotemia Renal Azotemia (Intrinsic) Postrenal (Obstructive)

Acute hemorrhage Acute glomerulonephritis Upper urinary tract obstruction (ureteral)

Gastrointestinal fluid loss

Interstitial nephritis (drugs, sepsis)

Lower urinary tract obstruction (bladder outlet)

Trauma and Surgery Acute tubular necrosis

Burns Ischemia

Low output syndrome Nephrotoxic drugs (antibiotics)

Renal artery stenosisSolvents (carbon tetrachloride, ethylene glycol)

Relative decrease Radiographic contrast dyesSepsis MyoglobinuriaHepatic failureAllergic reaction

Pre Renal Azotemia

Most common type

Designation for a rise in S.Cr, BUNdue to

inadequate renal plasma flow and hydrostatic

pressure

Intrinsic AKI

Sepsis

Ischemia

ischemia

Post operative AKI

Burns & acute pancreatitis

d/s of micro vasculature leading to ischemia

Nephrotoxin associated AKI

Nephrotoxin Contrast agents:m/c clinical course ,increase in

s.cr 24-48hrs,peaking with in 3-5 dys, resolving with in 1 week

Antibiotids

Chemotherapeutic

toxic ingestions

Endogenous toxins

Contrast agents

(1) hypoxia in the renal outer medulla due to

perturbations in renal microcirculation and

occlusion of small vessels;

(2) cytotoxic damage to the tubules directly or via

the generation of oxygen free radicals, especially

since the concentration of the agent within the

tubule is markedly increased; and

(3) transient tubule obstruction with precipitated

contrast material

contrast Prevention of radiocontrast nephropathy

depends on adequate hydration (e.g., 1 mL/kg normal saline initiated at least 4 hours before and continued for 12 hours after radiocontrastadministration)

Elective surgical procedures should be deferred until the effects of the dye have been evaluated and treated.

Nonionic, low-, or iso-osmolar radiocontrastmedia are less nephrotoxic but are expensive and offer optimal cost-benefit ratio when used in high-risk situations only

Prevention of CONTRAST

N acetyl cystein

fendolopam

Antibiotics & chemotherapy

Aminoglycosides andamphotericin B both cause

tubular necrosis

Cisplatin and carboplatin are accumulated by

proximal tubular cells and cause necrosis and

apoptosis

Ifosfamide may cause hemorrhagic cystitis and

tubular toxicity

Antiangiogenesis agents such as bevacizumab,

can cause proteinuria and hypertension via injury

to the glomerular microvasculature (thrombotic

microangiopathy).

Intrinsic AKI

Post renal

Pre operative evaluation

Most patient with ARF requiring surgery are

critically ill

Optimal perioperative management

dependent on preoperative dialysis

Preoperative dialysis on the day or previous

day of surgery

Physial and lab examination depend up on

cardiac and pulmonary function

Physical signs of fluid overload ,hypovolemia

Pre operative evaluation

Pre ,current and post dialysis weight

pre operative red blood cell transfusion

Drug therapy should be carefully reviewed

Investigations & Diagnostic Tools CBC - Anemia BUN (10-20 mg/dl) S.Creatinine (0.6-1.3 mg/dl) Creatinine clearence (110-150 ml/min) Serum Electrolytes- HyperK⁺ Urinalysis CXR ECG & ECHO ABG- Metabolic acidosis, hypoxemia, Imaging modalities

Urinary IndicesIndex Pre-renal Causes Renal Causes

Urinary sodium concentration (mEq/L) <20 >40

Fractional excretion of sodium (%) <1 >1

Urine osmolarity (mOsm/L) >400 250–300Urine creatinine/plasma creatinine >40 <20

Urine/plasma osmolarity >1.5 <1.1

Pre Anaesthetic Optimisation No specific treatment Symptomatic and supportive treatment- hypotension,

hypovolemia, low cardiac output state- maintenance of BP Treat underlying cause Correct fluids Diuretics Electrolytes and acid-base derangements Mannitol ??- pre ischemic insult, ↑PG-renal vasodilatation,

free radical scavenging, osmotic diuresis Low dose Dopamine?? N-acetylcysteine- free radical scavenger, (600 mg orally

BD)

Dialysis

Indication for dialysis

Fluid overload

Refractory GI symptoms

Hyperkalemia

Drug toxicity

Severe acidosis

Mb encephalopathy

Pericarditis

Coiagulopathy

AnaestheticConsiderations

Anaesthetic Problems & Concerns Fluid homeostasis -Hypotension, hypovolemia, CHF, HTN,

pulmonary edema, hypoalbuminemia Electrolyte disturbances - Hyperkalemia, hypocalcemia Acid-base disturbances - Metabolic acidosis, hypoxemia Delayed gastric emptying - ↑Aspiration Arrhythmias, conduction blocks Neurological complications Dilutional Anemia Infections Effect on drug handling

OpioidsMorphine Conj. to M-3-G, M-6-G

, active metabolite, respdepresion

Active metabolite has renal elimination, 40% conj occurs in kidney

Dose adjustment required

Meperidine(Pethidine)

Normeperidine, CNS toxicity

Active metabolite has renal elimination

Dose adjustment required

Fentanyl ↓ Plasma protein binding,↑ free drug

Clearance not altered safe

Sufentanil ↓ Plasma protein binding,↑ free drug

Clearance not altered safe

Alfentanil ↓ Initial vol of distribution,↑ free drug

Clearance not altered safe

Remifentanil No change Clearance not altered safe

Inhalation Agents Halothane Inorganic fluoride levels are less No Neprotoxicity

Isoflurane Inorganic fluoride levels are less No Neprotoxicity

Desflurane Inorganic fluoride levels are very less, highly stable & resists degradation by soda-lime & liver

No Neprotoxicity

Sevoflurane Inorganic fluoride levels are less but not stable , degraded by soda-lime to compound A & undergoes liver metabolism

Compound A is neprotoxic

Enflurane Biotranformed to inorganic fluoride levels after prolonged use (> 4hrs)

Nephrotoxic,afterprolonged use

Methoxyflurane Biotranformed to high inorganic fluoride levels Highly nephretoxic

Intravenous AgentsThiopentone CNS effect reversed by redistribution &

hepatic metabolism, also 80% protein bound, ↓albumin in uremia, ↑ free drug, more free un-ionised drug in acidosis

Metabolism unchanged ,↓ excretion,

Used in ↓ dose

Propofol Metabolised by liver No adverse effect

Etomidate Metabolised by liver, partial renal excretion

No adverse effect

Benzodiazepines Metabolised in liver & excreted by kidney, longer acting BZD accumulate, ↑duration of action

↑ Interval or ↓ dose

Local anaesthetics Dose reduction needed

Respiratory or metabolic acidosis increases the risks for CNS toxicity from local anesthetics

Elevated PaCO2 enhances cerebral blood flow and thus the anesthetic is delivered more rapidly to the brain. In addition, diffusion of carbon dioxide into neuronal cells decreases intracellular pH, which facilitates conversion of the base form of the drugs to the cationic form. The cationic form does not diffuse well across the nerve membrane, so ion trapping will occur, which will increase the apparent CNS toxicity of local anesthetics

Monitoring• All routine monitoring – ECG, NIBP, SpO₂, EtCO₂, NM

monitoring

• Monitoring urinary output and intravascular volume (desirable urinary output: 0.5 ml/kg/hr)

• Intra-arterial, central venous, pulmonary artery monitoring are often indicated

• Intra-arterial blood pressure monitoring in poorly controlled hypertensive patients

Pre-Medication Reduced doses of an opioid or BZD,

H2 blocker - Aspiration prophylaxis,

Metoclopramide -10 mg for accelerating gastric emptying, prevent vomiting, ↓risk of aspiration,

Antihypertensive agents should be continued until the time of surgery.

InductionPatients are at increased risk of aspiration: rapid-sequence

induction with cricoid pressure.

Drugs Normal Dosages Altered DosagesThiopental 3-5 mg/kg 2-3 mg/kgPropofol 1-2 mg/kg 1-2 mg/kgEtomidate 0.2-0.4 mg/kg 0.2-0.4 mg/kgSuccinylcholine 1-2 mg/kg 0.5-1.5 mg/kgAtracurium 0.6 mg/kg 0.6 mg/kgCisatracurium 0.15 mg/kg 0.15 mg/kg

Maintenance Ideal maintenance - control hypertension with minimal

effects on cardiac output,

Controlled ventilation with cuffed endo-trachial tube should be considered for patients with renal failure,

Fluid therapy: D5W, isotonic crystalloids (lactated Ringer’s?, NS), colloids, pRBC,

Anaesthesia can be maintained with inhalation agents or propofol with muscle relaxants ↓NM monitoring.

Reversal• Neuro-muscular blockage is reversed with Neostigmine or

pyridostgmine in combination with anticholenergic.

• Neostigmine and pyridostgmine has 50% & 70% renal elimination respectively.

• Glycopyrolate has 80% renal excretion so should be used cautiously.

• Atropine undergoes 25% renal elimination and rest hepatic metabolism to form metabolite noratropine which has renal excretion.

• Extubation should be done after complete reversal of NM blockage.

Post Operative• Monitoring of fluid overload or hypovolemia titrated fluids,

• Residual neuromuscular blockade,

• Monitoring of urea and electrolytes,

• ECG monitoring for detecting cardiac dysrhythmias.

• Continue oxygen supplementation in post operative period,

• Analgesia with regional,

• Carefully titrated opioids, ↑CNS depression, respiratory depression – naloxone.

Drugs Drugs safe Drugs safe inlimited or

reduced doses

Drugs contraindicated

Premeditation Midazolam, Temazepam Diazepam

Induction Thiopental, Propofol, Ethiomedate

Ketamine

Maintenance Isoflurene, Desoflurne, Halothane, Propofol

Sevoflurene Enflurane, Methoxyflurane

Muscle Relaxants Sch*, Atracurium, Cistracurim

Vecuronium, Rocuronium

Pancuronium

Opioids Alfentanil, Remifentanil, Sufentanil

Fentanyl, Morphine Pethidine

Local Anaesthetic Bupivicaine, Lidocaine

Analgesic Paracetamol NSAIDS

summary

Patients presenting for surgery with renal

insufficiency or failure present a significant

challenge for the anesthesiologis

It is imperative that the anesthesiologist not only

understands the management of these complex

patients but also intervenes to prevent further

renal injury during the perioperative period.

Judicious fluid management,the maintenance of

normovolemia, and avoidance of hypotension are

priorities for the successful prevention of further

renal injury

References• Miller RD. Anesthesia. 7th ed. NY: Churchill

Livingstone Inc.; 2010. Anesthesia and the Renal and Genitourinary Systems, 2105-2134.

• G.Edward morgan 4h edition,746-751

• Stoelting’s Anesthesia & Co-existing Disease, 5th ed. Renal Disease,358-384.

• Harrison’s Principles of internal medicine, 18th ed. Approach to a Patient with Renal Disease and Renal Failure,2293-2299

Thank you..