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Chronic Renal Failure, peri-operative management of patients for renal transplantation including CRRT Dr. Devika Agarwal University College of Medical.

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Presentation on theme: "Chronic Renal Failure, peri-operative management of patients for renal transplantation including CRRT Dr. Devika Agarwal University College of Medical."— Presentation transcript:

1 Chronic Renal Failure, peri-operative management of patients for renal transplantation including CRRT Dr. Devika Agarwal University College of Medical Science & GTB Hospital, Delhi

2 Scope of this presentation
Chronic Renal Failure Definition of chronic renal failure Causes and patho-physiology Key peri-operative issues Effect on anaesthetic drugs Peri-operative management Anaesthetic management of renal transplant CRRT

3 Definition of CRF Chronic 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 ml/min/1.73 m2 ) Stage 3 Moderate (GFR of ml/min/1.73 m2 ) Stage 4 Severe (GFR of ml/min/1.73 m2 ) Stage 5 ESRD (GFR of <15 ml/min/1.73 m2 ) or on dialysis

4 Causes of chronic renal failure

5 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)

6 Pathophysiology of CRF And its implications for

7 Perpetuating triad of chronic kidney disease, anaemia, and cardiovascular disease
Perpetuating triad of chronic kidney disease, anaemia, and cardiovascular disease (LVH=left ventricular hypertrophy; LVD=left ventricular dilatation)‏ Parmar M S BMJ 2002;325:85-90 ©2002 by British Medical Journal Publishing Group

8 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

9 Strategies for active management of chronic renal disease
Strategies for active management of chronic renal disease (BP=blood pressure; Ca=calcium; CRF=chronic renal failure; EPO=erythropoietin; ESRD=end stage renal disease; GN=glomerulonephritis; GFR=glomerular filtration rate; Hb=haemoglobin; PO4=phosphate; RRT=renal replacement treatment)‏ ©2002 by British Medical Journal Publishing Group Parmar M S BMJ 2002;325:85-90

10 Key peri-operative issues

11 Remember in Peri-operative work-up
Anaemia Neuropathy Platelet dysfunction Immunosupression Electrolyte imbalance Coronary artery disease Hypervolemia/CHF Metabolic acidosis Gastroparesis

12 Hematologic issues in CRF
ANAEMIA 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

13 Increased 2,3 DPG levels (chronic adaptation)
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 g/dl

14 Hematologic issues in CRF
Coagulation 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 complications CAUSES: Urinary loss of antithrombin Decreased levels of protein C and S Hyperfibrinogenemia Impaired fibrinolysis Increased platelet aggregability Seen in patients with nephrotic syndrome

15 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

16 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 wave Wide QRS QRS merges T (sine waves) AV dissociation , VT,VF, cardiac arrest

17 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 min.

18 Treatment of hyperkalemia
Potassium movement into the cells Insulin and glucose – - 25 to 50 gram glucose with units of regular 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/L Sodium bicarbonate infusion- Most useful in metabolic acidosis with hyperkalemia Watch for sodium overload and volume expansion in CRF

19 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 min, duration 2-4 hr. Decreases potassium levels by 0.5 to 1.5mEq/L Loop diuretics Furosemide mg iv

20 Metabolic Acidosis Mild to moderate acidosis - GFR less than 20-25% of normal pH> 7.2 with plasma bicarbonate 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

21 Effect on commonly used anaesthetic drugs

22 Effect of ESRD on anaesthetic drug metabolism
Pharmacokinetics Absorption - affecting by delayed gastric emptying Distribution – 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

23 Inhalational anaesthetics
fluoride levels Nephrotoxic potential Halothane 1-2 μM/L No Isoflurane 3-5 μM/L Desflurane <1 μM/L after 1MAC-hr Sevoflurane 50 μM/L prolonged use Toxic in animal studies

24 Intravenous induction agents
Renal 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 Increased unbound fraction of thiopentone due to reduced protein binding and acidosis promotes ionisation

25 Neuromuscular Blockers
NMB 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

26 Neuromuscular Blockers
CLINICAL IMPLICATIONS IN CRF PATIENTS Increased Volume of distribution Reduced metabolism and Excretion of drugs Avoid long acting NMBs Larger initial dose to produce NM blockade reduced maintainence dose Neuro-muscular monitoring

27 Clinical implications
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 Remifentanyl Meperidine Normeperidine causes seizures, myoclonus, altered sensorium Avoid in CRF Tramadol O-demethyl tramadol, 30% renal excretion Best avoided, dosing interval increased

28 Non opioid analgesics NSAIDS contraindicated Hyperkalemia
Platelet dysfunction Inhibit production of PGE2 and PGI2 Acetaminophen – safe perioperatively

29 Local Anaesthetics Shortened duration due to altered protein binding
Dose reduced by 25% Risk of epidural hematoma

30 Preoperative evaluation

31 Clinical history History related to present surgical condition
History related to kidney disease: Cause Duration Treatment Dialysis/ICU or hospital admission

32 Symptoms of CRF Malaise Weakness Fatigue Neuropathy CHF Anorexia
Nausea Vomiting Seizure Constipation Peptic ulceration Diverticulosis Anemia Pruritus Jaundice Abnormal hemostasis

33 Past history- H/O comorbid conditions - Htn , Diabetes, HIV, Polycyctic kidney disease, obstructive uropathy Onset Progession Treatment – drugs, compliance, control complications

34 History of dialysis Dementia Cerebral edema
Hypovolemia (hypotension after anaesthesia induction) Peritonitis (peritoneal dialysis) Systemic anticoagulation

35 History of dialysis Time since last dialysis –
last dialysis should finish atleast 4-6 hrs prior to allow fluid shifts and elimination of heparin within 24 hrs of surgery Post dialysis status Full blood counts BUN, S.Cr, electrolytes Coagulation Patient’s weight Dialysis related complications -

36 Family h/o kidney disease, HT, DM
Personal history- Smoker Alcohol Drug abuse

37 Examination Blood pressure Flow murmurs Pericadial rub
Ankle/ sacral edema Pulmonary edema Fistula

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

39 Chest X-ray Pulmonary edema Cardiomegaly Pericardial effusion

40 Anaesthetic management

41 Anaesthetic management
Pre-op preparation optimize BP, B.sugar Correct serum potassium ABG Aspiration prophylaxis – metoclopramide and H2 antagonist

42 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

43 Maintenance of anesthesia
O2 + N2O + isoflurane + Atracurium / cis-atracurium Controlled ventilation Monitors: ECG NIBP / IABP Capnography Pulse oxymery Temp Neuromuscular monitoring CVP Urine output

44 Restricted fluids Forced air warming and fluid warming Emergency preparedness

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

46 Perioperative management renal transplantation
of patient with renal transplantation

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

48 Criteria for kidney donation
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 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

49 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

50 Donor matching Ideal match: donor and recipient same phenotype
ABO blood group: Ideal match: donor and recipient same phenotype Compatible 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

51 Cross matching: Recipient’s antibody response to donor HLA antigens
Antibody produced after pregnancy or blood transfusion (positive cross-match - relative contraindication to transplant)

52 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

53 Method of transport Cadaver kidney:
Donor kidney flushed with cold storage solution + packed in sterile container with ice In a machine that pumps preservation solution through organ Living donor kidney Preservation solution/ iced Ringer lactate with heparin and mannitol (ischemia time: 20 – 30 min)


55 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

56 Dual kidney transplant-
More blood loss / third space loss Longer duration

57 Preoperative preparation
Preop work up for comorbidities Workup for chronic renal failure + Urine analysis and urine culture

58 Intraoperative management
GA preferred – longer operative time, blood loss, good muscle relaxation RA – not preferred Uremic bleeding tendency Residual effect of heparin post dialysis

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

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

61 Reasons for decline of CVP after revascularization :
Redistribution of fluids Changes in vascular permiability Increased nitric oxide levels

62 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

63 Induction of anaesthesia
Induction of immuno-suppression started before entering operating room Standard anaesthesia monitors Central line and arterial-line placed

64 IV induction with reduced dose of thiopentone /propofol /etomidate:
Lower plasma protein levels 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.

65 Blunt laryngoscopic response
fentanyl 5mc/kg iv – metabolised in liver with only 7% renal excretion Remifentanyl (metabolized by plasma esterase) and alfentanyl (metabolized by liver) can also be used Esmolol 0.5 – 1.0 mg/kg

66 Rapid sequence induction using succinylcoline/rocuronium
increase in serum potassium by 0.5 to 1.0 mEq/l within 3-5min and lasting min Succinylcoline can be safely used in renal failure if serum potassium is < 5.5 mEq/l and repeated doses avoided Plasma cholinesterase levels are 20% less – rarely causes prolonged block

67 Maintenance of anaesthesia
Volatile anaesthetic- sevoflurane – renal toxicity due to production of fluoride and compound A isoflurane and desflurane- can be used safely Muscle relaxant – atracurium, cisatracurium – hoffman elimination mivacurium – decreased activity of pseudocolinesterase Pancuronium- dependant on renal clearance

68 Intraoperative fluids
Avoidance of potassium containing fluids Normal saline and albumin 5% preferred CVP cm H2O Furosemide/ mannitol to improve urine output Estimated blood loss – 200 – 500 ml Larger losses replaced with RCC that is CMV negetive

69 Intra-operative effect of polyclonal and monoclonal antibodies
Anaphylaxis Stop ATG administration Continue mechanical ventilation with 100% oxygen antihistamines,steroids and epinephrine Patients on beta blockers or ACE inhibitors may not respond to therapy Prevention: antihistamines, acetaminophen and steroids before injection

70 Perioperative oligouria
Oligouria is urine output of less than 0.3mg/kg/hr Low urine output indicates dramatic reduction in glomerular filteration rate or mechanical obstruction

71 Peri-operative renal dysfunction
Type 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

72 Continuous renal replacement therapy

73 Indications of renal replacement therapy
Classical indications Volume overload leading to heart failure, pulmonary edema or severe hypertension Anuria Hyperkalemia (> 6.5 mEq/L) Metabolic acidosis (pH < 7.1) Symptomatic uremia (encephalopathy, pericarditis, blood dyscrasias) Dialysable intoxicants Lithium - Aspirin Ethylene glycol - Theophylline Methanol

74 Indications of renal replacement therapy
Alternative indications Endotoxic shock Hypothermia (rewarming) Nutritional support Delibrate hypothermia Traumatic rhabdomyolysis Plasmapheresis (Gullian Barre syndrome, myasthenia gravis, TTP

75 Modes of renal replacement therapies
Intermittent (<24 hrs) Intermittent hemodialysis (IHD) Sustained low-efficiency dialysis (SELD) Extended daily dialysis (EDD) Intermittent and continuous Peritoneal dialysis (PD) Continuous Continuous ambulatory peritoneal dialysis (CAPD) Continuous renal replacement therapy

76 Continuous renal replacement therapy
Slow continuous hemofiltration (SCHF) Continuous venovenous hemofiltration (CVVH) Continuous venovenous hemodialysis (CVVHD) Continous venovenous hemodiafiltration (CVVHDF)

77 Processes of renal replacement therapies
Ultrafiltration: Blood is pumped to a filtering membrane Hydrostatic pressure is higher on the blood side of the filter Leaves cellular material behind

78 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

79 2. Convection: Independent of any solute gradient
Dependent on porosity

80 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)

81 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

82 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

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

84 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 care Most efficient approach

85 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

86 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

87 (a) A pressure sensor to
detects any decrease in pressure (e.g. vascular catheter blockage). (c) distal to the drip chamber Detects reduced flow if the return catheter port is blocked. (b) A post-filter sensor detects reduced flow to the drip chamber,


89 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

90 Thank you

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