Chronic Renal Failure, peri-operative management of patients for

renal transplantation including CRRT

Dr. Devika Agarwal

University College of Medical Science & GTB Hospital, Delhi

Scope of this presentationChronic Renal Failure• Definition of chronic renal failure• Causes and patho-physiology• Key peri-operative issues• Effect on anaesthetic drugs• Peri-operative managementAnaesthetic management of renal transplantCRRT

Definition of CRFChronic renal failure is a decline in the glomerular filteration rate secondary to various diseases such as diabetes, glomerulonephritis and PCKD

Stages of CRF (National Kidney foundation Staging System):Stage 1 kidney damage with normal or increased GFR (>90

ml/min/1.73 m2 Stage 2 Mild (GFR of 60-89 ml/min/1.73 m2 )Stage 3 Moderate (GFR of 30-59 ml/min/1.73 m2 )Stage 4 Severe (GFR of 15-29 ml/min/1.73 m2 )Stage 5 ESRD (GFR of <15 ml/min/1.73 m2 ) or on dialysis

Causes of chronic renal failure

Common causes of CRF

• Diabetes Mellitus (40%)• Hypertension (27%)• Chronic Glomerulonephritis (13%)• Cystic Kidney Disease (3.5%)• Interstitial nephritis (4%)• Others (obstructive uropathy, lupus

nephritis, HIV)

Pathophysiology of CRF And its implications for

anaesthetist

Perpetuating triad of chronic kidney disease, anaemia, and cardiovascular disease

Parmar M S BMJ 2002;325:85-90

©2002 by British Medical Journal Publishing Group

Patho-physiological manifestations of CRF

Electrolytes Volume expansion, hyponatremia, hyperkalemia, metabolic acidosis, hyperurecemia,hyperphosphatemia, hypocalcemia

Cardiovascular HTN, LVH, CHF, pulmonary edema, cardiomyopathy,pericarditis, hyperdynamic circulation

Hematological Anaemia,B & T cell dysfunction, qualitative platelet dysfunction, bleeding diathesis

Musculoskeletal Muscle weakness

Neurological Encephalopathy, memory loss, seizures, peripheral neuropathy, myoclonus

Gastrointestinal Gastroperesis, uremic gastroenteritis, peptic ulcers,pancreatitis, nausea & vomitting

Strategies for active management of chronic renal disease

Parmar M S BMJ 2002;325:85-90©2002 by British Medical Journal Publishing Group

Key peri-operative issues

Remember in Peri-operative work-up

Anaemia

Platelet dysfunction

Coronary artery disease

Metabolic acidosisHypervolemia/CHF

Electrolyte imbalance

Immunosupression

Neuropathy

Gastroparesis

Hematologic issues in CRFANAEMIA

CAUSES:• Chronic blood loss• Hemolysis• Marrow supression by

uremic factors• Reduced erythropoetin

production• Aluminium toxicity• Chronic infection• Bone marrow fibrosis due

to hyperparathyroidism

Anaesthetic Implications:• Decreased oxygen delivery • Increased cardiac output• Cardiac enlargement• Angina• CHF• Impaired mental acquity• Impaired host defence against

infection

• Increased 2,3 DPG levels (chronic adaptation). Oxy-Hb dissociation curve shifted to right

• Routine transfusions- sensitisation to HLA antigens• Erythropoetin therapy – target hematocrit 36 –40%• Intraoperative transfusion – packed cells, washed RBCs (irradiated

and CMV negetive) for hypotension, hcrit < 15%

Patients with ESRD on hemodialysis require Hb levels 11-12 g/dl

Hematologic issues in CRFCoagulation abnormality

CAUSES:• Decreased platelet factor

III• Abnormal platelet

aggregation and adhesion• Impaired prothrombin

consumption

Anaesthetic Implications:• Regional anaesthesia:Weigh the risk vs benefit of epidural placement in uremia patients

Thromboembolic complicationsCAUSES:• Urinary loss of antithrombin• Decreased levels of protein C

and S• Hyperfibrinogenemia• Impaired fibrinolysis• Increased platelet aggregability

Seen in patients with nephrotic syndrome

Hyperkalemia• Serum potassium > 5.5 mEq/L• Impaired renal excretion in CRF• Peri-operative aggrevating factors:

- Hemolysis- Hemorrhage- Massive blood transfusion- Metabolic acidosis (every 0.1 unit change in blood pH

increase K+ by 0.6 mEq/L- Rhabdomyolysis- Succinylcholine- Beta blockers, ACE inhibitors

ECG findings in hyperkalemia

Serum Potassium

ECG changes

•6-7 mEq/L

•7-8 mEq/L

•8-10 mEq/L

• >9 mEq/L

Tall T waves

loss of P waveWide QRSQRS merges T (sine waves)AV dissociation , VT,VF, cardiac arrest

Treatment of hyperkalemia

• Antagonism of membrane effects of hyperkalemia Calcium gluconate – - 10 ml of 10% solution over 5-10 min- Dose can be repeated if no change in ECG after 5-10 min- decreases membrane excitability- Can exacerbate digitalis induced arrythmia calcium

gluconate given in 100 ml D5% over 20-30 min.

Treatment of hyperkalemia

• Potassium movement into the cells Insulin and glucose – - 25 to 50 gram glucose with 10-20 units of regular insulin @

100 ml/hr- Insulin shifts potassium into the cells- Onset in 15 min,peak in 60 min,duration 4-6 hr.- Decreases potassium levels by 0.5 to 1.5mEq/LSodium bicarbonate infusion-- Most useful in metabolic acidosis with hyperkalemia- Watch for sodium overload and volume expansion in CRF

Treatment of hyperkalemia

• Potassium movement into the cells Beta adrenergic agonists - 20 mg in 4ml saline nebulisation over 10 min / 0.5 mg iv- shifts potassium into the cells- Onset in 30-60 min, duration 2-4 hr.- Decreases potassium levels by 0.5 to 1.5mEq/LLoop diuretics- Furosemide 20-40 mg iv

Metabolic Acidosis

• Mild to moderate acidosis - GFR less than 20-25% of normal

• pH> 7.2 with plasma bicarbonate 12- 22 mEq/L• bicarbonate correction - based on space of distribution of

bicarbonate 70% lean body weight with target bicarbonate level of 24 mEq/L

Bicarbonate replacement = 0.7 x wt(kg) x (24 – serum bicarbonate) half corrected

• If pH<7.2 dialysis

Effect on commonly used anaesthetic drugs

Effect of ESRD on anaesthetic drug metabolism

PharmacokineticsAbsorption - affecting by delayed gastric

emptyingDistribution – volume of distribution is

increased or decreased depending on total body water, protein binding and time since last dialysis

Elimination – prolonged half life for drugs with renal elimination. Eg. Vecuronium

Inhalational anaestheticsInhalational anaesthetic

fluoride levels Nephrotoxic potential

Halothane 1-2 μM/L No

Isoflurane 3-5 μM/L No

Desflurane <1 μM/L after 1MAC-hr No

Sevoflurane 50 μM/L prolonged use Toxic in animal studies

Intravenous induction agentsIntravenous induction

agentRenal effects Clinical implication

Thiopentone •Modest decrease in RBF and GFR•Increased unbound fraction

Induction and maintenance dose reduced

Propofol •Cloudy urine due to urates•Green urine due to phenols

•Does not adversely affect renal function

Etomidate •Metabolised by hydrolysis to inactive compounds

-

Ketamine •Does not alter renal function

•Does not alter renal function, not to be used in HTN

Neuromuscular BlockersNMB Renal effects Clinical implications

Scholine Hyperkalemia Avoid RSI if K+ > 5.5 mEq/L

Rocuronium 30% renal excretion

Modified RSI

Atracurium No renal metabolism

Laudanosine epileptogenic – prolonged surgery

Vecuronium 30% Renal excretion

Avoid in CRF

Pancuronium 50% Renal excretion

Avoid in CRF

Neuromuscular Blockers

CLINICAL IMPLICATIONS IN CRF PATIENTS

Increased Volumeof distribution

Larger initial dose to produce NM blockade

Reduced metabolism and

Excretion of drugs

reduced maintainence dose

Avoid long acting NMBs

Neuro-muscularmonitoring

Opioid Analgesics

Opioid Renal effects Clinical implications

Morphine M-6-G renal excretion Delayed respiratory depression

Fentanyl 7% renal metabolism Safe in CRF

Alfentanyl No renal metabolism Safe in CRF

Remifentanyl No renal metabolism Safe in CRF

Meperidine Normeperidine causes seizures, myoclonus, altered sensorium

Avoid in CRF

Tramadol O-demethyl tramadol, 30% renal excretion

Best avoided, dosing interval increased

Non opioid analgesics

• NSAIDS contraindicated- Hyperkalemia- Platelet dysfunction- Inhibit production of PGE2 and PGI2• Acetaminophen – safe perioperatively

Local Anaesthetics

• Shortened duration due to altered protein binding

• Dose reduced by 25%• Risk of epidural hematoma

Preoperative evaluation

Clinical history

History related to present surgical conditionHistory related to kidney disease:• Cause• Duration• Treatment• Dialysis/ICU or hospital admission

Symptoms of CRF

• Malaise• Weakness• Fatigue• Neuropathy• CHF • Anorexia• Nausea• Vomiting

• Seizure• Constipation• Peptic

ulceration• Diverticulosis• Anemia• Pruritus• Jaundice• Abnormal

hemostasis

• Past history-H/O comorbid conditions -Htn , Diabetes, HIV, Polycyctic kidney disease, obstructive uropathy

OnsetProgessionTreatment – drugs, compliance,

controlcomplications

History of dialysis

1. Dementia2. Cerebral edema3. Hypovolemia (hypotension after

anaesthesia induction)4. Peritonitis (peritoneal dialysis)5. Systemic anticoagulation

History of dialysis

• Time since last dialysis – last dialysis should finish atleast 4-6 hrs prior to allow fluid shifts and elimination of heparinwithin 24 hrs of surgery

• Post dialysis status - Full blood counts- BUN, S.Cr, electrolytes- Coagulation- Patient’s weight• Dialysis related complications -

• Family h/o kidney disease, HT, DM• Personal history-

– Smoker– Alcohol– Drug abuse

Examination

• Blood pressure• Flow murmurs• Pericadial rub• Ankle/ sacral

edema• Pulmonary edema• Fistula

Investigations• Full blood counts – normocytic normochromic anaemiaRaised TLC• Coagulation profile• KFT – BUN, S.Cr, S.E• ECG – ischemia, arrythmia, LVH• CXR • ABG – metabolic acidosis• LFT – if major surgery

Chest X-rayPulmonary edema

Cardiomegaly

Pericardial effusion

Anaesthetic management

Anaesthetic management

Pre-op preparation- optimize BP, B.sugar- Correct serum potassium- ABG- Aspiration prophylaxis – metoclopramide

and H2 antagonist

Intraoperative management

• Preoxygenation• Premedication – opioid (fentanyl)• Iv induction gradual and titrated• RSI – Sch if K+ < 5.5 mEq/L- modified RSI with rocuronium- Intubate controlled ventilation- Regional anaesthesia – risk of epidural

hematoma

Maintenance of anesthesia• O2 + N2O + isoflurane + Atracurium / cis-

atracurium• Controlled ventilation

Monitors:• ECG• NIBP / IABP• Capnography• Pulse oxymery

• Temp• Neuromuscular monitoring • CVP• Urine output

• Restricted fluids• Forced air warming and fluid warming• Emergency preparedness

Post operative care

• Analgesia- NSAIDS avoided- Paracetamol safe• Oxygenation• Monitoring – ECG, BP, SPO2, Urine output• Early mobilisation and chest physiotherapy

Perioperative management of patient with

renal transplantation

• Kidney donors• Contraindication for kidney donation• Donor matching• Preservation and transport• Surgical aspects• Peri-operative management• Post-operative oligouria

Kidney transplant

• Ideal donor- Age: 5 to 49 years- non hypertensive- Cause of death was not cerebrovascular accident- S. creatinine < 1.5 mg/dl

• Expanded criteria donor– Age: >60 years or 50-59 yr – additional risk factors (h/o HTN, death from cerebrovascular

accident or S.creatinine>1.5 mg/dl)70% risk of renal failure within 2 years

Criteria for kidney donation

Contraindications to receiving kidney transplant

Absolute• Recent or metastatic

malignancy• Untreated current infection• Severe irreversible non renal

disease• Psychiatric illness• Recreational drug abuse• Limited irreversible

rehabilitative potential• Infection: hetatitis B,C, HIV

Relative• Vesical or urethral

abnormalities• Aortoiliac occlusive disease• Morbid obesity• smoking

Donor matching

• ABO blood group: Ideal match: donor and recipient same phenotypeCompatible match: person with grp A may donate to A or AB

• Tissue typing: – HLA compatibility- Kidney with least number of

mismatches is prefered– With immunosupressive drugs recipients can receive an

organ with less than perfect match

• Cross matching: – Recipient’s antibody response to donor HLA

antigens– Antibody produced after pregnancy or blood

transfusion(positive cross-match - relative contraindication

to transplant)

Preservation and transport

• Temperature: 4*C – metabolic rate slowed 12 fold

• Cold storage solutions: - electrolyte composition similar to intracellular environment (low sodium, high potassium)

• Cold ischemia time: <36 to 40 hours

Cadaver kidney:– Donor kidney flushed with cold storage

solution + packed in sterile container with ice– In a machine that pumps preservation solution

through organLiving donor kidney

– Preservation solution/ iced Ringer lactate with heparin and mannitol (ischemia time: 20 – 30 min)

Method of transport

Surgical aspects

• Heterotopic position• Retroperitoneal – preferred- percutaneous

biopsy• Right or left ileac fossa• Inflow vessel - internal/ external ileac

artery • Outflow vessel -external ileac vein• Urinary continuity - to prevent reflux• Intraarterial injection of verapamil/

papaverine to prevent vasospasm (cadaveric donor)• Furosemide(200mg) frequently after

revascularisation

• Dual kidney transplant-– More blood loss /

third space loss– Longer duration

Preoperative preparation

• Preop work up for comorbidities

• Workup for chronic renal failure+ Urine analysis and urine culture

Intraoperative management

GA preferred – longer operative time, blood loss, good muscle relaxation

RA – not preferred• Uremic bleeding tendency• Residual effect of heparin post dialysis

Intra-operative monitoring

Routine monitoring-Heart rate-Blood pressure-ECG-pulse oximetry-capnograph-Neuromuscular monitoring

CVP monitoring- Rationale- adequate hydration , prevent ATN- CVP guided fluid therapy – 12- 14 cm H2O - Post dialysis patients have intravascular fluid

depletion

Invasive monitoring

Reasons for decline of CVP after revascularization :

1. Redistribution of fluids2. Changes in vascular permiability3. Increased nitric oxide levels

Invasive blood pressure monitoring:- Indicated in patient with advanced co-morbidities- Hypotension may occur after unclamping of iliac

vessels and/or partial systemic absorption of vasodilators (verapamil or papaverine)

- Hypotension can cause delayed graft function

Induction of anaesthesia

• Induction of immuno-suppression started before entering operating room

• Standard anaesthesia monitors• Central line and arterial-line placed

• IV induction with reduced dose of thiopentone /propofol /etomidate:

1. Lower plasma protein levels 2. Post dialysis hypovolemia

Some studies have suggested increased dose requirement of propofol due to hyperdynamic circulation in uremic patients

Ketamine undesirable in patients due to underlying hypertension.

• Blunt laryngoscopic response - fentanyl 5mc/kg iv – metabolised in liver with only

7% renal excretionRemifentanyl (metabolized by plasma esterase) and

alfentanyl (metabolized by liver) can also be used- Esmolol 0.5 – 1.0 mg/kg

• Rapid sequence induction using succinylcoline/rocuronium

- increase in serum potassium by 0.5 to 1.0 mEq/l within 3-5min and lasting 10-15 minSuccinylcoline can be safely used in renal failure if serum potassium is < 5.5 mEq/l and repeated doses avoidedPlasma cholinesterase levels are 20% less – rarely causes prolonged block

Maintenance of anaesthesia

• Volatile anaesthetic- sevoflurane – renal toxicity due to production of fluoride and compound Aisoflurane and desflurane- can be used safely

• Muscle relaxant – atracurium, cisatracurium – hoffman eliminationmivacurium – decreased activity of pseudocolinesterasePancuronium- dependant on renal clearance

Intraoperative fluids

• Avoidance of potassium containing fluids• Normal saline and albumin 5% preferred• CVP 12-14 cm H2O• Furosemide/ mannitol to improve urine

output• Estimated blood loss – 200 – 500 ml

Larger losses replaced with RCC that is CMV negetive

Intra-operative effect of polyclonal and monoclonal antibodies

Anaphylaxis 1. Stop ATG administration2. Continue mechanical ventilation with 100%

oxygen3. antihistamines,steroids and epinephrine

Patients on beta blockers or ACE inhibitors may not respond to therapy

Prevention: antihistamines, acetaminophen and steroids before injection

Perioperative oligouria

Oligouria is urine output of less than 0.3mg/kg/hrLow urine output indicates dramatic reduction in glomerular filteration rate or mechanical obstruction

Peri-operative renal dysfunctionType Cause Management

Pre-renal •Low intravascular volume•Relative decrease in blood volume (volatile anaesthetics

•Responds to fluid challenge

Renal •Structural- renal art. thr. , renal vein thr.•ATN -antibiotics, contrast dyes

Post-renal mechanical obstruction surgical wound closure impinging on graft vessels or ureter

-flush the foley’s catheter-Intraoperative ultrasound to examine flow at vascular anastomosis

Continuous renal replacement therapy

Indications of renal replacement therapy

Classical indications1. Volume overload leading to heart failure, pulmonary

edema or severe hypertension2. Anuria3. Hyperkalemia (> 6.5 mEq/L)4. Metabolic acidosis (pH < 7.1)5. Symptomatic uremia (encephalopathy, pericarditis, blood

dyscrasias)6. Dialysable intoxicants

– Lithium - Aspirin– Ethylene glycol - Theophylline– Methanol

Indications of renal replacement therapy

Alternative indications• Endotoxic shock• Hypothermia (rewarming)• Nutritional support• Delibrate hypothermia• Traumatic rhabdomyolysis• Plasmapheresis (Gullian Barre syndrome,

myasthenia gravis, TTP

Modes of renal replacement therapies

1. Intermittent (<24 hrs)• Intermittent hemodialysis (IHD)• Sustained low-efficiency dialysis (SELD)• Extended daily dialysis (EDD)2. Intermittent and continuous• Peritoneal dialysis (PD)3. Continuous• Continuous ambulatory peritoneal dialysis (CAPD)• Continuous renal replacement therapy

Continuous renal replacement therapy

• Slow continuous hemofiltration (SCHF)• Continuous venovenous hemofiltration (CVVH)• Continuous venovenous hemodialysis (CVVHD)• Continous venovenous hemodiafiltration

(CVVHDF)

Processes of renal replacement therapies

1. Ultrafiltration: • Blood is pumped to a

filtering membrane• Hydrostatic pressure

is higher on the blood side of the filter

• Leaves cellular material behind

2. Convection:• “solute drag”-

solute molecules swept through membrane by moving stream of ultrafiltrate

• Positive pressure - blood compartment

• negetive pressure -dialysate compartment

• Driving force = trans-membrane pressure

2. Convection:• Independent of any solute

gradient• Dependent on porosity

3. Diffusion:• Movement of solutes from

higher to lower concentration across an electrochemical gradient

• In hemodialysis dialysate is pumped countercurrent to blood flowing on other side of semi-permeable membrane

• Particle size (<20 KDa)

3. Diffusion:• Rate of diffusion

depends on – Solute (size, charge,

pr.binding)– Dialysis membrane

(porosity,thickness,surface area)

– Rate of delivery of solute– Conc. of dialysate

4. Membrane adsorption:• Adsorption on artificial

membranes• Determined by pore size

and surface area• Membrane’s adsorptive

capacity gets saturated in first hours of RRT

• Hemodialysis = Diffusion• Hemofiltration = Convection• Hemodiafiltration = diffusion + convection

Type of CRRT Principle Application

SCUF fluid load CHF

CVVH fluid and middle sized molecules

CVVHD mostly small molecules

CVVHDF Small and medium sized molecules

Intensive careMost efficient approach

Advantages of CRRT in critically ill patients

• Hemodynamically unstable patients• Precise volume control• Effective control of uremia, hyperkalemia and

hypophosphatemia• Rapid control of metabolic acidosis• Available 24 hours a day• Safe in patients with brain injury and cardiovascular disorders• Adjuvant therapy in sepsis

Dialysate and replacement fluid

• Initially dialysate low in intracellular ions (potassium, magnesium and phosphate is used)

• Normokalemic solution when serum potassium is < 4.5 mEq/L

(a) A pressure sensor todetects any decrease in pressure (e.g. vascular catheter blockage).

(b) A post-filter sensordetects reduced flow to the drip chamber,

(c) distal to the drip chamber Detects reduced flow if the return catheter port is blocked.

Further reading

• Miller’s anaesthesia , 7th edition• Clinical anaesthesia, Barash• Yao and artusio’s anaesthesiology, 6th edition• Harrison’s principles of internal medicine, 16th

edition• Parmar MS. Chronic renal disease BMJ 2002;

826: 86-90

Thank you