Optimization & perioperative

considerations
for patient with
renal disease.
Presentation by– dr.venkatesh .
Moderator – dr.jui.
Aims & objectives of perioperative management of
patients with renal dysfunction.
Proper assessment of the renal status of the
patient & its management.
AKI/CRI/ESRD/Acute on CRI
 Assessment & management of the multiple
comorbidity .
Prevent AKI in perioperative period.
To formulate an individualized & safe anesthetic
plan.
 Cardiovascular system considerations.
Systemic hypertension – most common; multiple
antihypertensives(3/more); cause/effect; intractable.
 Contributes to CHF,CAD,cerebrovascular disease.
 Speeds up progressive ↓ GFR.
Accelerated atherosclerosis,PVD,fluid overload.
Uremic pericarditis/effusion/tamponade.
Causes – Na+ & H20 retention; RAA axis activation.
Arrhythmia,conduction blocks – dyselectrolytemia.
Respiratory system – acid –base imbalance; pleural
effusion,pulmonary
edema,pneumonia,pleuritis,interstitial & alveolar
edema,muscle wasting.

CNS - ↓ cognitive function, encephalopathy, peripheral

uremic neuropathy, autonomic dysfunction,myoclonus
lethargy/confusion,seizures.
GI – Uremia induced delayed gastric emptying,adynamic
ileus,frequent nausea/vomiting,hiccoughs,upper GI
bleed,ascites.
Endocrine – 2° hyperparathyroidism,glucose
intolerance,hypertriglyceridemia.
Musculoskeletal – muscle wasting & weakness,renal
osteodystrophy,periarticular calcification,pathological #.
Hematology –
 Anemia - ↓ erythropoietin,uremic bleeding(GI/epistaxis),
↓ RBC survival(frequent dialysis;circulating toxins),bone
marrow replacement by fibrous tissue (2°
hyperparathyroidism).
 Unresponsive to oral iron therapy.
 Uremic bleeding - ↑ bleeding tendency in presence of
normal laboratory coagulation study & PC (bleeding time
– best correlation).
 Impaired chemotaxis ,margination & phagocytosis - ↓
immunity.
Skin – pruritis(cutaneous Ca++
deposition),ecchymosis,hyperpigmentation.
Metabolic considerations –
 Acid – base disturbances – High AG MA(failure to
excrete non volatile acids).
 Hyperkalemia .
 Hypokalemia (net K deficit,dialysis,GI losses,diuretics).
 Hyponatremia.
 Hypomagnesaemia.
 Hyperphosphatemia.
 Hypocalcaemia.
 Hyperuricemia.
 Hypoalbuminaemia.
 Aluminium toxicity.
IMMUNE SYSTEM - considered immunocompromised.
 Prone for iatrogenic infection.
 Uremia causing leucocyte dysfunction.
 Dialysis,multiple transfusions – HBV,HCV,HIV infections
common.
 TB easily missed d/t similar symptoms.
 Preanesthesia evaluation.
HISTORY –
 Coexisting comorbidity – duration & severity.
 Duration,severity & treatment of renal impairment.
 Uremic symtoms.
 Daily fluid intake & urine output.
 Effort tolerance.
 Active infection.
 Previous anesthesia exposure – residual curarisation,drug
allergy.
 Medications.
 Timing & details of last dialysis.
 Preanesthesia evaluation.
PHYSICAL EXAMINATION –
 Pre & post dialysis weight.
 Hydration status,edema.
 Site & condition of dialysis access.
 Venous access.
 Fever.
 Vitals – HTN,orthostatic hypotension.
 Routine physical examination.
 Preanesthesia evaluation.
INVESTIGATIONS –
 Hgb/Hct.
 TC/DC/PC/BT.
 Blood sugars.
 Urine R/M; C/S.
 Coagulation profile.
 RFT.
 LFT.
 SE.
 ECG/ECHO.
 CXR.
 ABG.
 Screening for HBV,HCV,HIV.
 Preanesthesia advice.
Adequate NPO.
Antacids & prokinetics.
Dialysis within 24 hours prior Sx.
Post dialysis investigations.
Continuation/stoppage of medications.
Avoidance of sedatives.
Blood/blood products.
High risk consent with standby ICU bed.
 Monitoring.
Basic minimum monitors.
NIBP cuff – not over an AVF.
ABP,CVP & PAP if large fluid shifts suspected.
Accurate blood loss measurement.
UOP monitoring,ABG & GRBS.
Minimum FiO2 = 0.4
Maintainance of strict fluid balance & UOP ~ 0.5mL/hr.
Patient positioning w.r.t. AVF & frail patients succeptible for
# & frequent post operative neuropathy.
IV access – difficult,presence of AVF,hemodialysis access.
?Regional v/s General anesthesia.
Efficacy of local anaesthetic is reduced in acidosis
High incidence of haematoma due altered coagulation
profile.
No comparitive study demonstrating superior renal
protection or improved outcome with GA v/s RA.
Advantage of neuraxial blockade –
 sympathetic blockade of T4 – T10 segments 
suppression of sympathoadrenal stress response &
release of catecholamines, renin & AVP.
 RBF and GFR are preserved as long as adequate renal
perfusion pressure is maintained.
Pharmacological considerations in perioperative period.
1. Preservation of RBF and perfusion pressure.
2. Avoidance of excessive vasoconstriction.
3. Avoidance of nephrotoxic drugs &
4. Adjustment of the drug dosages(↑ VD & ↓ protein
binding).

Drug depending solely on renal clearance – calculated %

↓ in drug dosage matching ↓ in GFR(creatinine clearance
adjusted dose).
Drugs with less binding (Eg.Phenytoin) – normal serum
levels = dangerously high levels of active(unbound)
fraction.
 ANESTHETIC AGENTS IN RENAL DISEASE.
1. DIRECT EFFECTS – Most of agents used in GA – not
nephrotoxic.
 Exception – methoxyflurane & enflurane ( ‘fluoride
hypothesis’).
 High output renal insufficiency,unresponsive to
vasopressin(Sevoflurane – not associated with renal
concentrating defects).
 Presents as dilute polyuria,dehydration,hyperosmolarity &
elevated BUN/Sr.Creatinine.

2. INDIRECT EFFECTS - renal

vasoconstriction,hypotension,peripheral vasodilation,low
COP.
Site of metabolism –
intrarenal >>
extrarenal/hepatic.

Sevoflurane – compound A
– dose dependent
nephrotoxin in rats ;
Human studies – no renal
injury with/without renal
impairment with FGF < 1L.
 ANESTHETIC AGENTS IN RENAL DISEASE.
INDUCTION AGENTS & SEDATIVES.
1. Thiopentone - Free fraction of induction dose – almost
doubled in renal failure – exaggerated effects – substantial
reduction in induction dose in uremic patients.
2. Ketamine – less extensively protein bound than
thiopentone,renal failure – minimal influence on free
fraction.
 Redistribution & hepatic metabolism – termination of
action.
 <3% excreted unchanged in urine.
 Norketamine – major metabolite – 1/3rd activity –
metabolized & excreted by kidneys.
 ANESTHETIC AGENTS IN RENAL DISEASE.
INDUCTION AGENTS & SEDATIVES.
3. Propofol – extensive & rapid hepatic biotransformation
– inactive metabolites – renal excretion.
 Pharmacokinetics unchanged in renal failure,no
reports of prolongation of effects in ESRD.

4. Etomidate – 75% protein bound – larger free fraction in

ESRD patients - ↓ protein binding – no alteration of
clinical effects of etomidate induction.
 ANESTHETIC AGENTS IN RENAL DISEASE.
 INDUCTION AGENTS & SEDATIVES.
5. BZDs – extensively protein bound – CKD ↑ free fraction
→ potentiation of clinical effects.
 60 – 80% of midazolam excreted as its α hydroxy
metabolite – accumulates in renal failure especially in
long term infusions.
 Diazepam & lorazepam also carry a risk of active
metabolite induced sedation on repeated doses.
 Alprazolam - ↓ protein binding & ↑ free fraction – CKD
patients more sensitive to sedative effects compared
with healthy volunteers.
 ANESTHETIC AGENTS IN RENAL DISEASE.
OPIOIDS –
1. Morphine – single dose studies – no alteration in
disposition.
 Repeated doses – accumulation of 6-glucuronide
metabolite – potent analgesic,sedative & respiratory
depressant.
 ↓ protein binding in ESRD – reduction in initial
dosage.

2. Pethidine – neurotoxic metabolite(normeperidine) –

irritability,twitching & seizures - not recommended in
patients with poor renal function.
 ANESTHETIC AGENTS IN RENAL DISEASE.
OPIOIDS –
3. Hyromorphone – active metabolite(hydromorphone –
3 – glucuronide) excreted by kidneys – accumulation
→ cognitive dysfunction & myoclonus.
4. Codeine – potential for prolonged narcosis – not
recommended for long term use.
5. Alfentanil - ↓ protein binding but unchanged
elimination t1/2 & clearance in ESRD;extensively
metabolized to inactive compounds – caution in
loading dose but total dose & infusion rates
unchanged.
 ANESTHETIC AGENTS IN RENAL DISEASE.
OPIOIDS –
4. Fentanyl – lack of active metabolites,unchanged free
fraction & short redistribution phase – opioid of
choice.
 Small to moderate doses,titrated to effect – well
tolerated by uremic patients.
5. Sufentanil – free fraction unchanged but variable
pharmacokinetics – reported to cause prolonged
narcosis in ESRD.
 ANESTHETIC AGENTS IN RENAL DISEASE.
OPIOIDS –
5. Remifentanil – rapid metabolism by tissue/blood
esterases – weakly active( <4600 times) & renally
excreted metabolite(remifentanil acid).
 No effect of ESRD on clearance of remifentanil but
elimination of remifentanil acid markedly reduced –
unknown clinical implications.
 ANESTHETIC AGENTS IN RENAL DISEASE.
NEUROMUSCULAR BLOCKING AGENTS -
 Most likely group of anesthetic drugs to produce
prolonged effects in ESRD.
 Sch,atracurium,cis-atracurium & mivacurium – minimal
renal excretion of unchanged parent compound.
 Coexisting acidosis,electrolyte disturbance & drug
therapy(aminoglycosides,diuretics,immunosuppressants
& Mg++ containing antacids) alter pharmacodynamics in
patients with renal disease.
DRUG % RENAL T1/2 (Hr) Renally Use in ESRD.
EXCRETION Normal/ESRD excreted active
metabolite
d-TC 60 1.4/2.2 - Avoid
Metocurine 45 – 60 6/11.4 - Avoid

Pancuronium 30 2.3/4-8 + Avoid

Gallamine >85 2.5/6-20 - Avoid
Pipecuronium 37 1.8-2.3/4.4 + Avoid
Doxacurium 30 1.7/3.7 - Avoid
Vecuronium 30 0.9/1.4 + Avoid infusion

Rocuronium 30 1.2-1.6/1.6-1.7 - Variable

infusion
Atracurium & <5 0.3/0.4 - Normal
cis-atracurium
Mivacurium <7 2min/2min - 1.5 X normal
duration
Rapacuronium <12 0.5/0.5 ++ Normal single
dose
 ANESTHETIC AGENTS IN RENAL DISEASE.
NEUROMUSCULAR BLOCKING AGENTS -
1. Sch – Duration of action not significantly prolonged in
ESRD – use justified for RSI provided serum K+ is not
↑↑↑.
 Serum K+ to be normalized to extent possible prior Sch
administration.
 Continuous infusion – problematic d/t major
metabolite(succinyl monocholine) weakly active &
excreted by kidneys.
 Acute,small(~0.5mEq/L) elevations in serum K+ - well
tolerated by chronically hyperkalemic CKD subjects.
 ANESTHETIC AGENTS IN RENAL DISEASE.
NEUROMUSCULAR BLOCKING AGENTS -
2. Long acting – doxacurium,pancuronium &
pipecuronium – ↑ elimination t1/2,↓ plasma clearance
& prolonged duration of action - avoided in ESRD.
3. Atracurium – potential concern of accumulation of
neurotoxic metabolite laudanosine causing seizures in
experimental animals with repeated
dosing/continuous infusion.
4. Cis-atracurium – greater potency,lower dose
requirements – lower laudanosine blood
levels(theoretical advantage).
 ANESTHETIC AGENTS IN RENAL DISEASE.
NEUROMUSCULAR BLOCKING AGENTS -
5. Vecuronium – duration slightly prolonged in renal
failure d/t ↓ clearance & ↑ elimination t1/2.
 Intubating dose expected to last ~50% longer in ESRD.
 Potential for accumulation of 3-desmethyl
vecuronium(active metabolite) in anephric patients on
continuous infusion → prolonged NM blockade.
 ANESTHETIC AGENTS IN RENAL DISEASE.
NEUROMUSCULAR BLOCKING AGENTS -
6. Rocuronium – similar effects as vecuronium.
7. Mivacurium – slower recovery from bolus dose in
anephric patients d/t low pseudocholinesterase
activity.

 Pharmacokinetics of anticholinesterases – affected by

renal failure → prolonged duration of action d/t heavy
reliance on renal excretion.
 Similar effects on excretion of
anticholinergics(atropine/glycopyrrolate) → no dosage
alteration required in reversing patients with CRI.
Effects of various anesthetics on renal function.
Risk factors for perioperative aki.
Treatment algorithm for acute perioperative oliguria.
Occurrence of perioperative renal failure depends on –
1. The surgery.
2. Preoperative and intraoperative haemodynamics.
3. Preoperative renal condition(DM - 10 fold greater risk
of renal deterioration in the presence of hypovolemia).

 All intravenous and volatile induction agents → ↓ COP

& BP.
 High level of neuraxial block – upto T4 → ↓ sympathetic
tone to the kidneys → ↓ RBF & GFR.
 Mechanical ventilation with positive pressure also ↓ RBF.
Major surgery → extensive third space losses →
hypovolemia & renal hypoperfusion.
Pathogenesis of perioperative aki.
 Renal protection in perioperative period.
1. FLUIDS -
 Maintenance of RBF & GFR by adequate hydration →
prevent further renal injury & preserve renal function.
 Hydration → effective in prevention of contrast-induced
nephropathy & probably the best strategy to prevent
progression to frank renal failure.
 Renal protection in perioperative period.
2. DOPAMINE –
 RCTs & meta-analyses → no prophylactic/therapeutic
effect of dopamine on AKI.
 ↑BP/HR → improved perfusion pressures → ↑ UOP
explains the possible benefits of dopamine in
preventing AKI.
3. ACETYL CYSTEINE –
 Free radical O2 scavenger ; modulates NO synthesis after
oxidative cell stress.
 Efficacious in prevention of contrast-induced
nephropathy when given early before the insult.
 Renal protection in perioperative period.
4. BICARBONATE –
 Alkalinization of urine → ↑ solubility of myoglobin →
prevents formation of tubular precipitates → effective in
Rx of pigment-induced nephropathy(rhabdomyolysis).
 ↓ formation of nephrotoxic free
radicals(preferentially formed in acidotic
environments).
 ↓ formation of free radicals in contrast-induced
nephropathy as well → ↓ I/O CIN from 13.7% to 1.7%.
 Renal protection in perioperative period.
5. LOOP DIURETICS/MANNITOL –
 Rationale - to flush out casts of necrotic cells that may
obstruct renal tubules.
 Loop diuretics also ↑RBF through ↑ prostaglandin synthesis
and↓metabolic workload of the tubules by ↓ active sodium
reabsorption.
 Diuretics → hypovolemia & further exacerbate renal
hypoperfusion →imperative to ensure normovolemia before
their use.
Thank you.