Anaesthesia in Renal Failure

Nadia van Heerden

Kimberley Hospital Complex
30 January 2015
OVERVIEW
 Kidney Anatomy
 Renal Physiology
 Anaesthesia for Patients with Kidney Failure
 Chronic Kidney Disease
 Preoperative Evaluation
 Intraoperative Considerations
 Postoperative Considerations
 Pharmacological considerations
KIDNEY ANATOMY
KIDNEY BLOOD SUPPLY
Kidney Blood Supply
 Kidneys are the only organs for which oxygen consumption is
determined by blood flow
 Renal cortex - extracts little oxygen; high blood flow with
mostly filtration function
 Renal medulla – high metabolic activity dt solute
reabsorption and requires low blood flow to maintain high
osmotic gradients – RELATIVELY VULNERABLE TO
ISCHAEMIA
The Nephron: Functional unit of the
Kidney
 6 Major Anatomical and
functional divisions
 Glomerulus
 Proximal Convoluted
Tubule (PCT)
 Loop of Henle: descending
thin limb, ascending thick
and thin limb
 Vasa Recta
 Distal Convoluted Tubule
(DCT)
 Collecting Duct
Countercurrent Mechanism
 Countercurrent System:
ESTABLISHING & MAINTAINING MEDULLARY OSMOTIC GRADIENT
COUNTERCURRENT MULTIPLIER
Filtrate (isotonic) enters descending loop
Henle (water permeable; salt
impermeable)
Filtrate flows from cortex to medulla and
water leaves tubule by osmosis (ie filtrate
osmolality increases)
Ascending loop of Henle epithelium changes
to water impermeable and salt permeable
Salt leaves ascending limb and dilutes filtrate
Urea diffuses from lower portion of collecting
duct to contribute to high omolality in
medulla
DIFFERENT PERMEABILITIES OF 2 LOOPS
OF HENLE COOPERATE TO
ESTABLISH OSMOTIC GRADIENT IN
MEDULLARY INTERSTITIAL FLUID
COUNTERCURRENT EXCHANGE
Blood in vasa recta continuously
equilibrates with interstitial
fluid ie more concentrated as it
follows descending loop of
Henle and less concentrated as
it approaches the cortical region
 PREVENTS DISSIPATION
OF MEDULLARY OSMOTIC
GRADIENT
High porosity and sluggish
bloodflow in specialised vessels
 Renal Blood Flow
 20% of cardiac output goes to kidney
 Clearance: volume of blood that is completely cleared of a substance per unit
of time
 RPF most commonly measured by PAH clearance
 GFR: total amount of filtrate formed per minute by the kidneys
 Inulin (fructose polysaccharide) clearance a good measure (freely filtered; not
reabsorbed) but not practical
 Creatinine (product phosphocreatinine breakdown in muscle) clearance used; tends to
overestimate GFR (some creatinine normally secreted by renal tubules)
 Cockroft-Gault equation
 Factors governing filtration rate at capillary beds
 Total surface area available for filtration
 Filtration membrane permeability
 Net filtration pressure
 Ratio GFR to RPF called filtration fraction (FF); normally 20%
GFR
 GFR held relatively constant by 3 mechanisms that regulate
renal blood flow

1. RAAS (hormonal mechanism)

2. Neural controls (sympathetic nervous system controls)
3. AUTOREGULATION (intrinsic)
Extrinsic Neural Controls
LOW BP IN
RENAL Increased Increased
peripheral
BLOOD resistance systemic BP
VESSELS

GFR

EXTRINSIC Vaso-constriction of Renin release from

NEURAL systemic arterioles JG cells in kidney
CONTROLS
Increased blood
volume &
RAAS systemic BP

Baroreceptors in
bloodvessels of
SNS
systemic circulation
Autoregulation
 Kidney can maintain a nearly constant GFR despite fluctuations
in in systemic arterial BP
 Arterial pressure range from 80 to 180 mmHg
 Outside autoregulation limits RBF becomes pressure dependent
 Directly regulated the diameter of afferent (and lesser extent
efferent) arterioles
 Mechanism: 2 types of control
 Myogenic mechanism
 General tendency for vascular smooth muscle to contract when stretched
 Increased BP  afferent arterioles constrict (decreased blood flow into glomerulus) and decrease in
glomerular pressure
 Decreased BP  dilatation of afferent arterioles and increase in glomerular hydrostatic pressure
 Tubuloglomerular feedback mechanism
 Directed by macula densa cells of juxtaglomerular apparatus
 Located in walls of distal tubules – responds to filtrate flow rate and osmotic signals
 Either allows or prevents release of chemicals that produces intense vasoconstriction of afferent
arterioles
 Eg if macula densa exposed to slow flowing filtrate or low osmolarity filtrate vasodilatation of
afferent arterioles promoted ie allows more blood flow into glomerulus and therefore increases NFP
and GFR
 Main Functions of the Kidneys
 Salt & Water Balance or Homeostasis
 Toxin Removal
 Calcium & Phosphate Homeostasis
 Acid Base Homeostasis
 Stimulation of Erythropoiesis
Salt & Water Balance
 Water Homeostasis
 Controlled by ADH: Increase nr of aquaporins within
collecting ducts (Facilitates greater water reabsorption)
 Sodium Balance
 2 most NB mechanisms:
 RAAS: Aldosterone increases NA reabsorption by increases nr of NA channels
and Na pumps (DCT and collecting duct)
 ANP :Released with atrial stretch (salt &water overload) and Increases Na
excretion by INHIBITING the RAAS
 Potassium Balance
 K freely filtered by glomerulus and most of it reabsorbed by PCT (not
respond to differing plasma K concentration)
 DCT and collecting ducts regulates K balance
 Aldosterone : Stimulates K secretion by increasing Na reabsorption
 K-H exchange pump: Collecting duct stimulates pump in response to
hypokalaemia (H secreted into collecting duct in exchange for reabsorning K ions)
A
D
H
A
N
P
ALDOSTERONE
 Toxin Removal
• 2 Mechanisms:
- Filtration
- Secretion
• Most water soluble toxins e.g
creatinine are freely filtered and not
reabsorbed
• Ie the levels should remain
constant and at non-toxic levels in
blood unless
- Ingestion
- Production changes
- GFR changes
Calcium & Phosphate Homeostasis
Acid Base Homeostasis
 Bicarbonate Reabsorption

Distal nephron reclaims any HCO3 that remains in the filtrate after passing through PCT
Acid Base Balance
 Enzyme systems are very pH sensitive
 Excess acid generation by metabolism that body needs to excrete
 Vast majority excreted as CO2 in lungs but NB fraction
(phosphate and sulfate ions) excreted by collecting ducts
 Bicarbonate main buffer in human body
 When filtrate reaches the collecting ducts it is acidic (dt HCO3
reabsorption and NOT excretion of acid)
 H ions are actively secreted by H-K antiporter (urine acidity
would increase if H not buffered)
 All HCO3 has been reabsorbed ie H ions are now buffered
primarily by ammonia (metabolised glutamine) and filtered
phosphate ions
Stimulation of Erythropoiesis
 ANAESTHESIA FOR PATIENTS
WITH KIDNEY FAILURE

CKD

Preoperative Evaluation

Intraoperative
Considerations

Postoperative
Considerations

Pharmacologic
Considerations
CKD
 Incidence of ESRD (aka CRF) increasing worldwide – in USA
prevalence of ESRD more than doubled between 1990 and 2001
 4 –Year survival for ESRD patients in UK only 48%
 Approximately 26 million Americans have some form of CKD
(pre-dialysis kidney disease) and many remain undiagnosed
 The CKD patient population fits the “2nd hit injury” paradigm
because they have some stable chronic baseline organ dysfunction
that is disproportionately worsened when exposed to acute
physiologic stress such as hypotension, hypovolaemia, or drug
toxicity
Definition CKD
 2002 National Kidney Foundation Kidney Disease Outcomes
Quality Initiative (K/DOQI) guidelines proposed a 5 stage
classification for CKD based on GFR
 GFR < 60mL/min/1,73m2 for > 3 months where there is
evidence of kidney damage or
 Evidence of kidney damage for > 3 months based on pathologic
specimen, imaging or laboratory tests (e.g proteinuria)
irrespective of GFR
RIFLE criteria
Aetiology of CKD

Diabetic Hypertensive Glomerular

Nephropathy Nephrosclerosis Disease

Interstitial Vascular Inherited

Diseases of the Diseases of the Kidney
Kidney Kidney Diseases
Pathophysiology of CRF
Uraemia
 Refers to the multitude of (uncorrected) effects resulting from
 The inability to excrete products of metabolism of proteins and
amino acids
 Impaired wide range of metabolic & endocrine functions of the
kidney
 Usually seen when GFR <25mL/min
 GFR <10mL/min is dependent on RTT for survival
 RTT (renal replacement therapy)
 Haemodialysis
 Haemofiltration
 Peritoneal dialysis
 Renal transplantation
FLUID OVERLOAD & CHF ANAEMIA (Hb 6 – 8 g/dL)
HYPERTENSION (Na & H2O CARDIO
• Decreased EPO production
retention // altered RAAS) VASCULAR •GIT blood loss
PERICARDITIS (haemorrhagic •Haemodilution
uraemic) • BM suppression (rec infxn)
ARRYTHMIA (IHD & electr abn) PLATELET DYSFUNCTION
CONDUCTION BLOCKS • Increased bleeding time
VASCULAR CALCIFICATION • Consider when choosing
(increased Ca-PO4 product & PTH regional anaesthesia
conc.  bacterial endocarditis more LEUCOCYTE DYSFUNCTION
common in RRT pt) • Increased susceptibility infxn
ACCELERATED
ATHEROSCLEROSIS
URAEMIA
HYPERVENTILATION HAEMATO
• May require increased MV to LOGICAL
compensate for metabolic acidosis
INTERSTITIAL OEDEMA
• Increased alveolar to arterial gradient
 risk hypoxaemia
ALVEOLAR OEDEMA
PULMON
ARY
• Permeability alv-cap membrane
PLEURAL EFFUSION
 PERIPHERAL NEUROPATHY &
AUTONIMIC NEUROPATHY
• Delayed gastric emptying
• Postural hypotension
• Silent Myocardial Ischaemia
DIALYSIS PATIENTS
• Dialysis dementia
• Dysequilibrium syndrome
GASTRO
INTESTINAL
ANOREXIA & NV (malnutrition)
DELAYED GASTRIC EMPTYING (RSI)
HYPERACIDITY (PUD – PPI)
MUCOSAL ULCERATIONS
(urea mucosal irritant)
HAEMORRHAGE
ADYNAMIC ILEUS
GLUCOSE INTOLERANCE
NEURO • Peripheral insulin resistance
LOGICAL SECONDARY
HYPERPARATHYROIDISM
• Metabolic bone disease
• Osteopenia predispose to #
HYPERTRIGLYCERIDAEMIA
• Accelerated atherosclerosis
ENDOC
UREMIA RINE
ACIDOSIS
• Less clearance H and HAGMA
FLUID & ELECTROLYTE ABN’s
• Hyperkalaemia – NB acidosis (avoid
META hypercarbia in GA)
• Sodium balance – NB diuretic use
BOLIC and cardiac function
Ca & PO4 DERANGEMENT
Preoperative Evaluation

 Multidisciplinary approach involving anaesthetists, surgeons

and renal physicians
 Optimise medical condition & address potentially reversible
manifestations of uraemia
 Cardiorenal syndrome & Cardiovascular Risk
 Renal Risk Assessment and Interventions
 Dialysis and Renal Transplant Patients
 Basic outline of the “Premed”
 History & Physical Examination
 CVS & Respiratory system evaluation NB ?? Fluid overload
 Visidex (diabetic patients)
 Basic bloods
 FBC (Hb), U&E (postdialysis), INR/PTT (NB platelet dysfunction in
uraemia – count may be normal)
 CXR (clinical impression)
 ABG
 Acid-Base status (Resp. distress);oxygenation; ventilation
 ECG
 Echo -
 Blood transfusion – only in severe (symptomatic) anaemia
 Consider Anaesthetic Technique
Cardiorenal Syndrome

 Pathophysiological disorder of the heart and kidneys wherein

the acute or chronic deterioration of one organ results in
acute or chronic deterioration of the other
 Classified into 5 types
 Cardiovascular Risk
 High prevalence of cardiovascular disease and increased perioperative
morbidity
 Cardiovascular risk assessment according to ACC/AHA guidelines
 Surgical risk for noncardiac procedures
 Major risk factors (before elective surgery)
 Risk profile for surgery
 Risk with intended procedure
 Decompensated HF or unstable coronary syndromes  postpone procedure until
medical management optimised
 Intermediate/Minor risk factors (before elective noncardiac surgery)
 Functional capacity (METs- metabolic equivalents or tasks)
 Self-reported/treadmill testing
 6 METs – better prognosis; good functional capacity – proceed to surgery
 Poor functional capacity – investigate and optimise prior surgery
 Type of surgery
 Renal Risk Assessment and
Interventions (non-dialysis pt)
 Detailed Background History
 Co-morbidities
 Duration CKD
 Usual fluid intake
 Usual daily urine output
 Renal function (baseline & current)
 Urea & Creatinine
 GFR
 Electrolyte concentrations
 Na
K
 Renal Risk Assessment and
Interventions Cont..
 Uncomplicated cases
 Euvolaemic,
 Responsive to diuretic therapy with
 No significant electrolyte abnormalities and
 No bleeding tendencies
 Complicated cases
 Oedema, CHF, Pulmonary congestion or responsive to diuretic therapy
 cardiovascular evaluation
 IF Cardiovascular evaluation OPTIMAL – fluid overload can be attributed
to CKD
 Consider combination diuretics to achieve euvolaemia prior to surgery
 Consider preoperative dialysis
 Diabetes – greater tendency to volume overload or cardiovascular disease
 Advanced CKD with diuretic resistance and progressive oedema
 Dialysis and Renal Transplant Patients
 Extra Considerations
 Dialysis adequacy
 Preoperative dialysis needs
 Usually 12-24hr prior surgery
 Fluid depletion & redistribution, electrolyte disturbances & residual
anticoagulation from heparinisation
 Post dialysis U&E prior surgery – NB intraoperative cardiac dysrythmias
 Postoperative dialysis timing
 Dosage requirements for all medications
 Intraoperative considerations:
Kidney Failure
 Monitoring
 Risk thrombosis – BP cuff not on arm with AV fistula
 Continuous intraarterial BP in uncontrolled HPT
 Induction
 RSI in patient with N&V or GI bleed
 Induction dose adjustment
 Anaesthesia maintenance
 Control BP with minimal deleterious effect on CO
 Volatile agents, propofol & opioids (NB morphine effect prolonged)
 Ventilation control to avoid respiratory acidosis and alkalosis
 Hypercarbia may exacerbate existing acidaemia  circulatory depression & increase in
serum potassium
 Fluid therapy
 Replace insensible losses in superficial operations involving minimal tissue trauma
 Procedures associated with major fluid losses
 Isotonic crystalloids, colloids or both
 Ringers Lactate contains potassium  NB Hyperkalaemic patients
 Bloodtransfusions only as indicated
Postoperative Considerations
 Emergency surgery
 Postoperative cardiac assesssment
 Lack preoperative evaluation
 Diagnosis of postoperative MI should be based on combination of clinical,
laboratory & ECG evidence
 Environment
 Normal ward
 High Care/ICU
 Analgesia
 Regional anaesthesia reduces requirement for systemic analgesic drugs
 Epidurals potentially reduced incidence of postop respiratory complications and
VTE events
 Systemic anaglesia
 WHO pain ladder
 PO vs IMI vs PCA (IV)
 Immune Suppression with transplants – postoperative sepsis risk increase
 Pharmacological Considerations
 INTRAVENOUS AGENTS
 Induction Agents
 Muscle Relaxants
 Reversal Agents
 Benzodiazepines
 Opioids
 INHALATION AGENTS
 Volatile Agents
 Nitrous Oxide
 OTHER
 Induction Agents
PROPOFOL & Pharmacokinetics minimally affected and
ETOMIDATE pharmacodynamics unchanged
Changes in volume distribution and mental state
Decreased induction dose required

BARBITURATES Pharmacokinetics unchanged but

Increased sensitivity dt increased free circulating barbiturates
(decreased protein binding) and acidosis increases entry into brain
by increasing nonionised fraction

KETAMINE Pharmacokinetics minimally changed

Hepatic metabolites may depend on renal excretion and can
potentially accumulate
Muscle Relaxants
SUCCINYLCHOLINE Safe if HYPERKALAEMIA absent
CISATRACURIUM & DRUG OF CHOICE; plasma ester hydrolysis, nonenzymatic
ATRACURIUM Hoffman elimination
VECURONIUM Primary hepatic metabolism, 20% eliminated by kidneys. If use
>0,1mg/kg dose prolonged effect
ROCURONIUM Hepatic elimination but prolonged action in kidney disease
reported. Can be used if appropriate NM monitoring available
PANCURONIUM 60 – 90% dependant on renal excretion

Reversal Agents
NEOSTIGMINE Renal excretion. Halflife prolonged. Inadequate reversal
often related to other effects (“recurarizaton’)
ATROPINE & Safe for use.
GLYCOPYROLLATE Repeated doses potential for accumulation (50% drug excreted in
urine)
 Opioids
MORPHINE Active metabolites (morphine-6-glucoronide) may have
greater activity than parent drug and may accumulate
Start at lower suggested dosage and titrate dosage
upwards slowly and increase dose intervals
FENTANYL Inactivated by liver and excreted by urine
REMIFENTANYL Significant accumulation does not occur
ALFENTANYL No active metabolites

Benzodiazepines
MIDAZOLAM & Hepatic metabolism with urine elimination
DIAZEPAM Active metabolites accumulate
Protein bound ; increased sensitivity in
hypoalbuminaemic patients
Dose reduction 30 – 50%
Inhalation Agents

 Not dependent on renal function

 Sevoflurane and Enflurane may produce nephrotoxic fluoride
ions
 Some physicians avoid use in lengthy procedures
 Other
PHENOTHIAZINES Pharmacokinetics minimally altered but potentiation of
central depressant effect can occur
H2 RECEPTOR Depend on renal excretion
BLOCKERS Dose reduction required
PPI Dose adjustment not required
METOCLOPRAMIDE Accumulates in kidney failure
DOLASETRON Dose adjustment not required
NSAIDS Avoid in kidney disease
LOCAL ANAESTHETICS Decreased duration of action
Maximum dose to be decreased by 25% due to decreased protein
binding and lower CNS seizure threshold
Renal Protection: Pharmacological
Interventions
 Dopamine
 Volume management by increasingUO
 Evidence does not support “renal protective effect”

 Loop Diuretics – Furosemide

 Used to preserve intraoperative UO – high doses in ARF reduce need for dialysis (no improvement in
mortality)
 “Protective effect” only demonstrated in rodent models

 Osmotic Diuretic Mannitol

 Old data in kidney transplants – impaired renal perfusion with goal of renal protection and maintenance of
adequate UO
 Recent randomised trial failed to show protective benefit patients undergoing major vascular surgery

 ACE inhibitors
 No data to support benefit

 CCB’s
 Data insufficient to support benefit

 N -Acetyl Cysteine
 Prevention of contrast nephropathy (high risk in CKD)
 Combination with adequate hydration
 Data fails to show benefit when used as renoprotective agent during major surgery
References
 Butterworth JF, Mackey DC, Wasnick JD. Morgan and Mikhail’s Clinical Anaesthesiology
5th Edition. Ch 29 pg 631 – 652 (Renal Physiology and Anaesthesia) and Ch 30 pg 653 –
670 (Anaesthesia for patients with kidney disease) 2013 The McGraw Hill Companies,
Inc.
 Marieb EN. Human Anatomy and Physiology 5th Edition. Ch 26 pg 1013 – 1029 (The
Urinary System: kidney physiology) 2001 Pearson Education, Inc publishing as Benjamin
Cummings
 McPhee SJ & Papadakis MA. Lange Current Medical Diagnosis & Treatment. 2012
McGraw Hill Companies, Inc.
 Wallace K. Renal Physiology. Update in Anaesthesia (www.worldanaesthesia.org)
 Milner Q. Pathophysiology of chronic renal failure. British Journal of Anaesthesia 2003;
3; 130 – 133 (http://ceaccp.oxfordjournals.org)
 Salifu MO. Perioperative Management of Patients with Chronic Renal Failure. Jun 7
2013 (emedicine.medscape.com/article/284555)
 Rang ST, West NL, Howard J, Cousins J. Anaesthesia for Chronic Renal Disease and
Renal Transplantation. EAU-EBU Update Series 4 (2006) 246 – 256
 Eilers H, Liu KD, Gruber A, Niemann CU. Chronic kidney disease: implications for the
perioperative period. Minerva Anestesiologica 2010;76:725 – 736
 Google Images