Difference Between Skeletal Smooth and Cardiac Muscles
anaesthestic implications in a case of chronic kidneydisease
1. DEFINITION
The National Kidney Foundation and the Kidney Disease Outcomes
Quality Initiative define chronic renal disease as the
structural or functional renal tissue damage lasting for over
three months, manifested by structural or functional abnormalities,
or by a drop in the glomerular filtration rate less than 60ml/kg/1.73m2.
Any drop below this level represents a loss of more than 50% of the renal function
in an adult and is associated with an increased risk of disease progression
2. CLASSIFICATION OF CHRONIC KIDNEY
DISEASE (CKD)
STAGE GFR, ml/min per 1.73 M2
0 >90*
1 ≥90**
2 60–89
3 30–59
4 15–29
5 <15
*WITH RISK FACTORS FOR CKD .
**WITH DEMONSTRATED KIDNEY DAMAGE (e.g., PERSISTENT PROTEINURIA, ABNORMAL URINE
SEDIMENT, ABNORMAL BLOOD AND URINE CHEMISTRY, ABNORMAL IMAGING STUDIES).
SOURCE: MODIFIED FROM NATIONAL KIDNEY FOUNDATION. K/DOQI CLINICAL PRACTICE,GUIDELINES FOR CHRONIC KIDNEY DISEASE: EVALUATION,
CLASSIFICATION AND STRATIFICATION. AM J KIDNEY DIS 39:SUPPL 1, 2002.
3. LEADING CATEGORIES OF ETIOLOGIES
OF CKD*
DIABETIC GLOMERULAR DISEASE (30%)
GLOMERULONEPHRITIS
HYPERTENSIVE NEPHROPATHY
PRIMARY GLOMERULOPATHY WITH HYPERTENSION
VASCULAR AND ISCHEMIC RENAL DISEASE
AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
OTHER CYSTIC AND TUBULOINTERSTITIAL NEPHROPATHY
*relative contribution of each category varies with geographic region.
4. Complications of CKD
Cardiovascular system
• Salt and water retention, hypertension, and LVH
• Cardiomyopathy, congestive cardiac failure,
• Accelerated Atherosclerosis and stiffening of large arteries
• Altered lipoprotein metabolism
• Uraemic pericarditis
• Cardiovascular autonomic neuropathy with reduced baroreceptor sensitivity,
sympathetic hyperactivity, and parasympathetic dysfunction
• Anaemia
5. Complications of CKD contd..
Metabolic acidosis
• Bone resorption
• Muscle wasting, growth retardation
Musculoskeletal system
• Renal osteodystrophy
• Rhabdomyolysis after major surgery
Endocrine system
• Secondary and tertiary hyperparathyroidism, vitamin D deficiency
• Diabetes mellitus
Gastrointestinal system
• Delayed gastric emptying
• Anorexia, vomiting, malnutrition
• Reduced calcium absorption
6. Complications of CKD contd…
Immune system
• Immunosuppression due to uraemia or drugs
Fluid and electrolyte homeostasis
• Hyperkalaemia
• Volume overload
• Dehydration
Neurological abnormalities
• CNS changes : mild personality changes to asterixis, myoclonus, encephalopathy and convulsions.
• Peripheral neuropathy, glove and stocking sensory loss progressing to motor changes
Haemostasis and coagulation
• Uraemic thrombocytopathy
• Prothrombotic tendency/hypercoagulation and reduced fibrinolysis
• Vascular access thrombosis
7. PREOPERATIVE EVALUATION
• Whichever the type of surgery (emergency or programmed),the clinical history must be
carefully recorded.
• The clinical and paraclinical evaluation is limited to simple clinical data (i.e., vital signs,
general aspect, signs of hypervolemia) and simple paraclinical data such as blood test,
electrolytes (sodium, potassium, calcium and phosphorus), uroanalysis, coagulation
status, serum creatinine and electrocardiogram.
• The clinical record shall address active cardiac conditions (active or recent acute myocardial
infarction, decompensated heart failure, severe valve disease and complicated arrhythmias).
• The functional capacity should be established, expressed in metabolic equivalents (METs),
according to the classification of the American Heart Society (AHA)
• Patients with a functional capacity <4 METs usually require additional studies to assess the
cardiovascular risk such as the dipyridamole scan or Dobutamine stress
echocardiography.
12. Pharmacology
• In patients with CKD, the effect of altered clearance, the production and accumulation of active
metabolites, and the risk of aggravating pre-existing kidney disease on drug administration
must be considered.
• Dose adjustment is not usually necessary until the GFR is <50 ml/min/1.73 m2
13. LOCAL ANAESTHETICS
L.A. have two plasma protein binding sites: a high affinity, low capacity site on AAG (α1-acid
glycoprotein) and a low affinity, high capacity site on albumin.
The albumin binding site becomes increasingly important as the plasma concentration of the
local anaesthetic increases.
Metabolic acidosis increases the percentage of unbound drug and this effect is more
pronounced with bupivacaine.
The effect of these changes on the toxicity of local anaesthetics is unclear.
14. Inhalation Agents
• “All inhalation agents bio-transformed to non-volatile products of metabolism
which are eliminated by kidney , but reversal of CNS effect depends upon
pulmonary excretion”.
• All inhalation agents causes transient reversible ↓ of GFR, RBF, U/O, renal auto
regulation.
Miller RD. Anesthesia. 7th ed., Anesthesia and the renal and genitourinary systems, page 2113.
15. 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,after
prolonged use
Methoxyflurane Biotranformed to high inorganic fluoride levels Highly
nephretoxic
16. Intravenous Agents
Thiopentone 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
17. Neuromuscular blocking and reversal agents
When selecting a neuromuscular blocking agent(NMBA) for use in patients with CKD, we must consider :
• The impact of renal impairment on the elimination of the drug,
• The potential for drug accumulation with incremental doses, and
• The production of active metabolites.
Other factors include :
• The effect of acidaemia and
• Drug interactions on the intensity and duration of block.
In general, the initial dose required to produce neuromuscular block is larger in patients with CKD than
in normal subjects. But, with the exception of atracurium and cisatracurium, the dose required to
maintain block is reduced.
To prevent postoperative residual curarization (PORC), the anaesthetist should avoid using long-acting
NMBA, or agents which are excreted in part in the urine, and make routine use of neuromuscular
monitoring
18. Muscle Relaxants
Succinylcholine Metabolised by psedocholinesterase to non
toxic products which are excreted by kidney,↑
duration in ESRD, also ↓ psedocholinesterase in
uremia, Associated with rapid transient ↑K⁺
(0.5mEq/L)
Longer block in ESRD
& uremia,
Cautiously used in
hyperkalemia
Atracurium Degraded by enzymatic ester hydrolysis & non
enzymatic alkaline degradation (Hoffmann
elimination) to inactive products
Not dependent on
renal elimination
Mivacurium Metabolised by plasma psedocholinesterase Longer block in ESRD
Cis-atracurium 77% hoffmann elimination & 16% renal
elimination
Mild effect
Vecuronium 30% renal elimination Prolonged duration
Rocuronium ↑Vol of distribution, No change in clearence Prolonged duration
Pancuronium 40-50%renal excretion, partly via less active
3hydroxy pancuronium renal excreation
Prolonged duration
19. Neostigmine clearance is reduced and its half-life is prolonged in CKD. This may result in a
parasympathomimetic response, including bradycardia and AV block, especially when used in
combination with atropine rather than the longer-acting glycopyrronium.
Sugammadex is helpful in preventing PORC . It has got fewer side effects.
20. Analgesic agents
In administering analgesic agents, the anaesthetist needs to consider:
• The impact of renal impairment on the distribution and elimination of
the parent compound and hence the need for adjusting the dose or
dose interval;
• The formation of active metabolites; And the risk of compromising
residual renal function.
Analgesic nephropathy is mainly associated with prolonged use of
compound analgesics containing two antipyretic agents with caffeine or
codeine.
21. • Acetaminophen oral acetaminophen 40 mg/kg/day for 3 days in normal subjects and
patients with CKD produced no demonstrable change in glomerular or tubular function in
either group. Prolonged use of acetaminophen is associated with analgesic nephropathy, but
occasional or moderate use is safe and does not require dose adjustment even in perioperative
period.
• Non-steroidal anti-inflammatory agents :They exacerbate hypertension and precipitate
oedema, hyponatraemia, and hyperkalaemia. There is an increased risk of GI bleeding,
cardiovascular complications in this at risk population. They precipitate an acute decrease in
GFR and may also cause acute interstitial nephritis .
• The renal effects of the COX-2 inhibitors (rofecoxib) are similar to those of the non-selective
NSAIDs and hence outweigh any potential benefit in perioperative period.
22. Opioids
Opioids have no direct toxic effects on the kidney. They do, however, have an antidiuretic effect,
and they may cause urinary retention. Very rarely, their use has resulted in rhabdomyolysis.
Morphine is metabolized in the liver to Morphine-3-glucuronide, the major one, accounting for
70% of the dose. M3G antagonizes the analgesic effect of morphine, and is associated with
irritability and a lower seizure threshold.
Approx. 5% of a dose of morphine is metabolized to morphine-6-glucuronide (M6G), which has
potent analgesic properties and may result in delayed onset of sedation and respiratory
depression. The elimination of M6G is dependent on renal function, and in patients with renal
failure, its half-life is prolonged from 2 to 27 h.
The metabolite load from an equi-analgesic dose of morphine given by the oral route is greater
than that from the parenteral route, due to extensive first-pass metabolism.
In renal patients, the dose of morphine should be reduced and the patient carefully monitored for
signs of delayed onset respiratory
Fentanyl undergoes extensive hepatic metabolism with no active metabolites. Approximately
7% is excreted unchanged in the urine. Clearance is reduced in CKD.
23. Remifentanil is not dependent on renal function for elimination. It undergoes ester hydrolysis
and its main metabolite is minimally active . In patients on HD, remifentanil had a reduced
clearance and prolonged elimination halflife. A lower infusion rate is required, but recovery is not
significantly prolonged.
Tramadol: 30 % of tramadol is excreted unchanged in the urine. O-Demethyl tramadol is an
active metabolite which is excreted by the kidneys. Uraemia is associated with a lowered seizure
threshold, and tramadol may be epileptogenic in these circumstances.
Meperidine is metabolized to normeperidine which is dependent on renal function for
elimination. The use of meperidine in patients with CKD has been associated with seizures,
myoclonus, and altered mental state.
Codeine and dihydrocodeine are also best avoided as their elimination half-life is
significantly prolonged, and conventional doses have resulted in central nervous system
depression.
24. Opioids
Morphine Conj. to M-3-G, M-6-G
, active metabolite, resp
depresion
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
25. DRUGS USED OR ENCOUNTERED IN ANESTHESIA PRACTICE
THAT SIGNIFICANTLY DEPEND ON RENAL ELIMINATION
Completely Dependent Partially Dependent
Digoxin, inotropes (used frequently;
monitoring of blood levels indicated in
chronic renal failure)
IV anesthetics—barbiturates
Others—aminoglycosides, vancomycin,
cephalosporins, and penicillins
Muscle relaxants—pancuronium
Anticholinergics—atropine, glycopyrrolate
Cholinesterase inhibitors—neostigmine,
edrophonium
Others—milrinone, hydralazine,
cycloserine, sulfonamides, and
chlorpropamide
26. RENAL REPLACEMENT THERAPY
Indications:
• Volume overload
• Hyperkalemia
• Severe metabolic acidosis
• Symptomatic uraemia
• Intoxication of dialyzable substances
The patient with CRF on HD should undergo HD the day before elective surgery.
27. VASCULAR ACCESS
Maintenance of vascular access patency is of vital importance in patients with stage 5 CKD on
HD. Vascular Access may be either permanent or temporary.
Options for Permanent access include :
1. Native arteriovenous fistulae (AVF).
2. Arteriovenous grafts (AVG), and
3. Long-term catheters.
Temporary vascular access includes:
1. Acute short term non-cuffed catheters which may or may not be tunnelled;
2. Long-term tunnelled cuffed catheters; and
3. S.C. Portcatheter systems
Complications relating to vascular access are a leading cause of hospitalization, morbidity and
the need for anaesthesia in patients with Stage 5 CKD. These include infection, stenosis,
thrombosis, aneurysm, limb ischaemia, limb oedema, heart failure, pulmonary atheroembolism,
steal syndrome, and recirculation.
28. PERIOPERATIVE FLUID MANAGEMENT
• Non invasive operations require replacement of only sensible water losses with
5% glucose in water ( 5-10 ml/kg iv). The small amount of urine output can be
replaced with 0.45% NaCl.
• Thoracic or abdominal surgeries can be associated with loss of significant
intravascular fluid vo;ume to the interstitial spaces. This loss is often replaced
with balanced salt solutions or 5% albumin .
• Blood transfusions must be considered when O2 carrying capacity is to be
increased or if blood loss is excessive.
• Measuring CVP may be useful in guiding fluid replacement.
29. INTRAOPERATIVE MANAGEMENT
GOALS
• Appropriate intravascular volume replacement
• Avoidance of nephrotoxic drugs
• Urinary catheter aiming for a urine output of >0.5ml/kg/hr
• Maintenance of a suitable intraop MAP
• Monitoring CVP
• Anticipation of anaesthetic and surgically induced hemodynamic pertubations
30. CHOICE OF ANAESTHESIA
• Regional anesthesia : Neuraxial anesthesia may be considered in patients with CKD. A
sympathetic blockade of T4 to T10 levels may theoretically improve renal perfusion by
attenuating catecholamine induced renal vasoconstriction and suppressing the surgical stress
response. However, platelet dysfunction and the effects of residual heparin in patients receiving
hemodialysis must also be considered. In addition, adequate intravascular fluid volume must be
maintained to minimize hypotension.
• Brachial plexus blockade is useful for placing the vascular shunts necessary for long-term
hemodialysis. In addition to providing analgesia, this form of regional anesthesia abolishes
vasospasm and produces vasodilation that facilitates the surgical procedure.
• The presence of uremic neuropathies should be excluded before induction of regional
anesthesia. Co-existing metabolic acidosis may decrease the threshold for seizures in response
to local anesthetics.
31. 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.
32. 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
33. ASSOCIATED CONCERNS
• Attention to patient positioning on the operating room table is important. Poor
nutritional status renders the skin particularly prone to bruising and sloughing,
and extra padding is required to protect vulnerable nerves around the elbows,
knees, and ankles.
• Fistulas must be protected at all costs and be well padded to prevent pressure
injury. Blood pressure cuffs should not be applied to the arm with the fistula. If
at all possible, the arm with the fistula should not be tucked but should be
positioned so that the fistula thrill can be checked periodically throughout
surgery.
34. Induction
Patients are at increased risk of aspiration: rapid-sequence induction with cricoid
pressure.
Drugs Normal Dosages Altered Dosages
Thiopental 3-5 mg/kg 2-3 mg/kg
Propofol 1-2 mg/kg 1-2 mg/kg
Etomidate 0.2-0.4 mg/kg 0.2-0.4 mg/kg
Succinylcholine 1-2 mg/kg 0.5-1.5 mg/kg
Atracurium 0.6 mg/kg 0.6 mg/kg
Cisatracurium 0.15 mg/kg 0.15 mg/kg
35. 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, colloids, pRBC,
• Anaesthesia can be maintained with inhalation agents or
propofol with muscle relaxants ↓NM monitoring.
36. 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.
37. POSTOPERATIVE MANAGEMENT
• Admission to ICU may be suitable for patients with significant comorbidities and after major
surgeries
• Post op cardiac assessment must be performed and continued for 3-5 days with daily ECGs and
screening of cardiac enzymes to detect and treat perioperative MI which most frequently occurs
within 72 hrs and are often silent yet quite fatal.
• HD should be ideally delayed till the risk of fluid shifts and hemorrhage has fallen ( some suggest at
least 24 hrs )
• Close attention to fluid electrolyte balance. CVP to be kept between 10-12 cm of H2O
• Multimodal analgesia : PCM is safe and effective . Intraoperative LA infiltration is simplest and
easiest but often inadequate and with finite duration.
• Medications for HTN, IHD etc should be re established to pre operative normalcy as soon as possible.
• For abdominal surgery patients placing feeding tubes facilitate drug administration even in presence
of reduced gastric emptying
39. .
1 MET to 4 METs >4METs Over 10 METs
Can take care of
him/herself?
Climb a flight of stairs? Swim or run fast?
Get dressed on his/her
own?
Walk 100 blocks? Plays a basketball
game, run long
distances at 10
km/h, row or
participate in
competition sport?
Walk at home on level
ground?
Plays tennis doubles?
Climbs two steps? Does heavy household
chores: moves heavy
furniture?
Do household chores:
sweep the floors or wash
dishes?
