ANESTHETIC AGENT OF CHOICE IN RENAL DISEASE

INTRODUCTION

• There are different types of renal diseases in varying severity .
• Patient can present with severe systemic illness significantly increasing anesthetic risk
• In general renal diseases are divided into 2 main types
• Acute kidney injury (AKI) is a common perioperative problem.
• Patients may develop AKI and kidney failure secondary to intrinsic kidney disease
• Chronic kidney disease is defined by the Renal Association as an abnormality of kidney structure or function that lasts more than 3 months.
• Patients in end-stage renal disease (ESRD) and chronic renal failure (CRF) present a number of challenges to the anesthesiologist.

​

​

AKI

Key Clinical Features of AKI

1. Urinary Changes

• Oliguria: Urine output < 0.5 mL/kg/hr; common early sign

• Anuria: Complete absence of urine in severe cases

• Dark or concentrated urine: May indicate hematuria or myoglobinuria

2. Fluid and Electrolyte Imbalance

• Edema: Swelling in legs, ankles, or feet due to fluid retention

• Pulmonary edema: Shortness of breath from fluid overload

• Hyperkalemia: Elevated potassium levels, risking arrhythmias

• Metabolic acidosis: Due to impaired acid excretion

3. Systemic Symptoms

• Fatigue and weakness: From uremia and electrolyte disturbances

• Nausea and vomiting: Common in uremic states

• Confusion or altered mental status: Especially in severe uremia

​

DIAGNOSIS

Drug Dosing in Patients With Renal Impairment

• The first step in tailoring drug dosing for patients with renal impairment is to estimate the creatinine clearance rate of elimination of drugs excreted by the kidneys ∝ GFR.

If the normal drug regimen starts with a loading dose to rapidly achieve therapeutic levels, the following guidelines may be used:

• If extracellular fluid volume appears to be normal - loading dose suggested for patients with normal renal function.
• If the extracellular fluid is contracted - reduce the loading dose.
• If the extracellular fluid is expanded - higher loading dose.

​

Management of Anesthesia

• Only life saving surgeries are done.
• Maintenance of an adequate systemic blood pressure and cardiac output
• Avoidance of further renal insults like hypovolemia, hypoxia, and exposure to nephrotoxins.
• Invasive hemodynamic monitoring is mandatory
• Frequent blood gas analyses and electrolyte measurements.
• Administration of diuretics to maintain urine output in patients who are not oliguric has not been shown to improve either renal outcome or patient survival.
• When a dilutional anemia has been caused by overzealous hydration, use of diuretics may minimize the risk of fluid overload caused by administration of blood or blood products.
• For patients who meet the criteria, postoperative dialysis should be initiated as soon as the patient is in hemodynamically stable condition.

CHRONIC KIDNEY DISEASE

• Chronic kidney disease (CKD) is marked by the presence of kidney damage (usually defined as estimated GFR < 60 mL/ min) for 3 or more months.
• In most patients, regardless of the cause, a decrease in GFR to less than 25 mL/min results in end-stage renal disease (ESRD) requiring dialysis or transplantation

​

• Patients who are undergoing dialysis require special consideration with respect to drug dosing intervals.
• Supplemental dosing may be needed for drugs that are cleared by dialysis.
• Drug doses are best scheduled for after completion of a dialysis session.
• Drug properties that influence clearance by dialysis include protein binding, water solubility, and molecular weight.

Perioperative hemodialysis

• Patients should undergo adequate dialysis within 24 hours of elective surgery to minimize the likelihood of volume overload, hyperkalemia, and uremic bleeding.
• Use of heparin may be avoided or minimized during preoperative hemodialysis.
• Patients on peritoneal dialysis who are undergoing abdominal surgery are generally switched to hemodialysis in the immediately postoperative period
• Urgent hemodialysis is not required after radiocontrast dye studies in those who are undergoing regular hemodialysis.

​

Management of Anesthesia

Preoperative evaluation

• Consideration of renal function
• Underlying pathologic processes, and comorbid conditions.
• Evaluate preexisting renal dysfunction- high risk of perioperative renal failure
• Serum creatinine concentration - determine renal function
• Blood volume status - comparing body weight before and after hemodialysis
• Measuring vital signs with particular attention to orthostatic hypotension or tachycardia.
• Glucose management
• Blood pressure should be well controlled before elective surgery.
• Antihypertensive therapy is frequently continued; however, ACE inhibitors and ARBS are often withheld on the day of surgery
• Preoperative medication must be individualized, with recognition that these patients may exhibit unexpected sensitivity to CNS depressant drugs
• Sr. Potassium concentration < 5.5 meq/L on the day of surgery

• Preoperatively for the presence of anemia, but the introduction of recombinant human erythropoietin therapy has decreased the number of patients with renal failure who come for elective surgery with a hematocrit of less than 30%.
• Preoperative coagulopathy - administration of desmopressin 0.3 μg/kg intravenously
• Dose reduction is also recommended with coinduction techniques, e.g., midazolam + opioids (fentanyl, sufentanil) because of limited cardiovascular reserve.
• Ketamine is not affected by renal failure and is a useful agent for emergency anesthetic induction

EFFECTS OF DRUGS IN PATIENTS WITH REDUCED RENAL FUNCTION

Premedication

• Because of the susceptibility of the uremic patient to excessive sedation and respiratory depression, premedication should be kept to a minimum
• A small dose of a short-acting anxiolytic (e.g., midazolam) is appropriate for the alert, oriented, and anxious patient.
• Glycopyrrolate is preferred to atropine and scopolamine to minimize anticholinergic CNS effects
• Gastric aspiration prophylaxis - especially in diabetic patients.
• H2-receptor blockers are excreted renally , therefore dosage adjustment is required.

INDUCTION OF ANESTHESIA

• Induction of anesthesia and tracheal intubation can be safely accomplished with most IV induction agents

THIOPENTONE:

• Thiopental is 75% to 85% bound to albumin,the concentration of which may be markedly reduced in uremia.
• Highly bound drug, reduced binding permits a greater proportion of an administered dose of thiopental to reach receptor sites.

​

• ​

​

• Weak acid -- acidosis ---> more un-ionized, nonbound, active thiopental
• Increase in the free fraction of thiopental from 15% in normal patients to 28% in patients with CRF.
• Dose should be reduced.

Propofol

• Does not adversely affect renal function as reflected by measurements of creatinine concentration.
• Prolonged infusions - excretion of green urine (phenolic metabolites)in the urine.
• Urate excretion is increased - cloudy urine when urate crystallizes under conditions of low ph and temperature.
• Because of the greater ease of reversibility of the potent inhaled anesthetics versus intravenous drugs, inhaled anesthetics may offer some advantages for the induction of general anesthesia in uremic patients

Muscle relaxants and their antagonists

• Succinylcholine can be used.
• Metabolism catalyzed by pseudocholinesterase to yield the nontoxic end products succinic acid and choline.
• The metabolic precursor of these two compounds, succinylmonocholine - excreted by the kidneys.
• Large doses ,prolonged infusion - should be avoided

​

​

• Although pseudocholinesterase levels are reduced in uremia these reductions are insufficient and cause a prolonged block.
• Hemodialysis has been reported to have no effect on cholinesterase levels.
• Administration of succinylcholine causes a rapid, transient increase of 0.5 mEq/L in the serum potassium concentration.
• In traumatized, burned, or neurologically injured patients, the increase may be 5 to 7 mEq/L, probably as a consequence of denervation supersensitivity of the muscle membrane to succinylcholine and to acetylcholine,can result in cardiovascular collapse.

​

​

Pancuronium

• Excreted in urine.
• Excreted after biotransformation to the less active metabolite 3-hydroxypancuronium.
• Prolonged terminal elimination half-life.

Atracurium

• Degraded by enzymatic ester hydrolysis and nonenzymatic alkaline degradation (hofmann elimination) to inactive products that are not dependent on renal excretion for termination of action.
• Laudanosine, an epileptogenic, by-product of atracurium metabolism is known to accumulate in crf and may be of concern in prolonged surgery.

Vecuronium

• 30 % eliminated by the kidneys
• Duration of neuromuscular blockade prolonged in patients with renal failure than in patients with normal renal function

Mivacurium

• metabolized by plasma pseudocholinesterase.
• Its effect has been shown to be lengthened by 10 to 15 minutes in patients with ESRD, due to decrease in plasma cholinesterase activity in these patients associated with uremia or hemodialysis

Rocuronium

• elimination half-life of rocuronium is increased in renal failure because of an increase in the volume of distribution with no change in clearance

​

​

​

.

• 50% of neostigmine and 70% of pyridostigmine and edrophonium excreted in urine.
• Excretion of all the cholinesterase inhibitors is delayed in patients with impaired renal function.

Inhaled Anesthetics

• All inhaled anesthetics are biotransformed to some extent, with the nonvolatile products of metabolism eliminated almost entirely by the kidney.
• Desflurane is highly stable and resists degradation by soda lime and the liver.
• prolonged inhalation of sevoflurane Plasma inorganic fluoride concentrations approaching nephrotoxic levels (50 μmol/L)
• sevoflurane can safely be delivered at fresh gas flows as low as 1 L/min without significant production of a breakdown product named compound A which is considered potentially nephrotoxic.

OPIOIDS:

MORPHINE: predominantly metabolised in the liver to morphine -3-glucuronide(M3G) & about 5 % to morphine 6 glucuronide (M6G)

• M6G has potent analgesic properties which is responsible for delayed onset of sedation & respiratory depression
• M6G get eliminated by the kidneys and so in patients in CRF, it can accumulate and the half life may prolong from 2 to 27 hours
• In patients with CRF; the dose and frequency of morphine should be reduced and patient should be monitored for delayed respiratory depression postoperatively.
• ​

​

FENTANYL: extensive hepatic metabolism with no active metabolites.

• Approx 7% is excreted unchanged in urine.

ALFENTANIL & REMIFENTANIL : can be administered safely

TRAMADOL: metabolised to O-Demethyl tramadol,which is excreted by kidneys

• 30% is excreted unchanged by kidneys
• It may be epileptogenic in these patients as uremia further lowers the seizure threshold

MEPERIDINE: metabolised to normeperidine associated with seizures,myoclonus& altered mental status.

CODEINE & DIHYDROCODEINE: best avoided as their elimination half life is significantly prolonged.

Vasopressors and antihypertensive drugs

• More than 90% of the thiazides and 70% of furosemide are excreted by the kidneys
• Propranolol is almost completely metabolized in the liver
• Esmolol is biodegraded by esterases in the cytosol of red blood cells
• Calcium channel–blocking agents nifedipine, verapamil, and diltiazem are extensively metabolized in the liver to pharmacologically inert products; they can be administered in usual doses to patients with renal failure
• Nitroglycerin can be useful because it is metabolized rapidly, with less than 1% excreted in urine

​

​

• Intermediate in the metabolism of sodium nitroprusside- cyanide
• Thiocyanate - final metabolic product.
• Half-life > 4 days, prolonged in renal failure.
• Thiocyanate levels > 10 mg/100 ml
• Hypoxia, nausea, tinnitus, muscle spasm, disorientation, and psychosis
• Hydralazine is slower acting its action is terminated by hydroxylation and subsequent glucuronidation in the liver, with approximately 15% excreted unchanged in urine.
• The elimination half-life of hydralazine is prolonged in patients with uremia
• Labetalol 0.5 mg/kg similar in patients with ESRD and in healthy volunteers
• If administration of a vasopressor is necessary, a direct α-adrenergic–stimulating drug such as phenylephrine would be effective.
• It causes the greatest interference with renal circulation.
• Although β-adrenergic–stimulating drugs such as isoproterenol maintain heart and brain perfusion without renal vasoconstriction, they also increase myocardial irritability.
• When possible, it is best to substitute simple measures such as blood volume expansion for drug therapy. If these measures are inadequate, β-adrenergic–stimulating drugs or dopamine should be used

​

• ​

Iv fluids

• Normal saline if na <140meq/l
• Half NS (0.45%nacl) if na >140meq/l

Exogenous na (FFP)

• 5% dextrose in NS or ½ NS in nondiabetic patients
• Excessive fluid and sodium intake quickly results in hypervolemia, pulmonary edema, and hypertension.
• Administration of excessive low sodium fluids results in hyponatremia.
• An overdialyzed anuric patient may appear to be dehydrated, yet pulmonary edema may be induced by positive fluid balance of as little as 500 ml.

​

REFERENCES

• Miller’s Anesthesia NINTH EDITION
• Morgan & Mikhail’s CLINICAL ANESTHESIA 5^TH EDITION
• Stoelting’s ANESTHESIA AND CO-EXISTING DISEASE 7^TH EDITION
• Anesthesiology Clinics of North AmericaVolume 18, Issue 4, 1 December 2000, Pages 863-882

​

THANK YOU