ARC Journal of Anesthesiology Volume 3, Issue 1, 2018, PP 9-14 ISSN 2455-9792 DOI: http://dx.doi.org/10.20431/2455-9792.0301003 www.arcjournals.org

Anesthesia Consideration for Renal Disease

Bhavna Gupta1*, Lalit Gupta2 1Senior Resident, Department of Anesthesia and Critical Care, Maulana Azad Medical College and LokNayak hospital, New Delhi, India 2Assistant professor, Department of Anesthesia, Maulana Azad Medical College and LokNayak Hospital, New Delhi, India

*Corresponding Author: Bhavna Gupta, Senior Resident, Department of Anesthesia and Critical Care, Maulana Azad Medical College and LokNayak hospital, New Delhi, India, Email: bhavna.Kakkar @gmail.com

Abstract: Anesthesia for renal disorders is described in detail in this review article.

1. INTRODUCTION  Normal renal function is important for the Kidneys is located in posterior abdominal wall, excretion of anesthetics and medications, th th maintaining fluid and acid base balance, and with 11 and 12 ribs and diaphragm placed posteriorly. It is 10 cm in length, 5 cm in width regulating hemoglobin levels in the and 3 cm in thickness. perioperative period. Sympathetic stimulation-is provided by  Renal disease is quite prevalent in patients preganglionic fibers T8-L1. Parasympathetic presenting for surgery and is associated with innervation is provided via vagus and s2-s4 increased likelihood of poor postoperative segments that supply the ureters. outcomes. Even mild renal dysfunction is associated with a more likely risk of Nociceptive stimulation is via sympathetic innervation T10-L1 in kidneys and T10-L2 in postoperative complications. ureters. Ureters receive sympathetic innervation The glomerular filtration rate (GFR) is a via T10-L2 via aortico-renal and superior and measure of glomerular function expressed as inferior hypogastric plexus. Pain is therefore milliliters of plasma filtered per minute and is usually referred to the lower back, flank, heavily influenced by arteriolar tone at points ilioinguinal region and scrotum or labia. upstream (afferent) and downstream (efferent) Kidney is amongst the vital organs of the body. from the glomerulus. Its functions include filtration of plasma,  Glomerular Filtration Rate is defined as maintaining water, osmolality, acid base balance volume of fluid which is filtered from the and electrolytes balance. Production of urine glomerular capillaries into bowman capsule begins with water and solute filtration from per unit time. It is measured as milliliters plasma flowing into the glomerulus via the per minute or ml/min. Normal range of GFR afferent arteriole. Kidneys also secrete renin and regulates fluid and blood pressure. It also adjusted for body surface area is 100 secretes erythropoietin. Conversion of 25 ml/min/1.73 m2 in men and 120 hydroxycholecalciferol to 1, 25 ml/min/1.73 m2 in females younger than 40 dihydroxycholecalciferol (vitamin D) is also years. GFR is 110 ml/min/1.72m2 in mediated in proximal renal tubules. Kidneys are children until 2 years of age and it also involved in metabolism and excretion of progressively decrease after that. After the many drugs. age of 40 years, GFR progressively decrease by 0.4-1.2 ml/min/year. GFR is often used Renal blood flow (RBF) = 20-25% of CO (80% for classifying chronic Kidney Disease cortical nephrons, 20% medullary) with Auto (CKD): (Table1) regulation of RBF @ MAP of 80-180 mm Hg. ARC Journal of Anesthesiology Page |9 Anesthesia Consideration for Renal Disease

Table1. Classification of CKD with respect to GFR Stage Description GFR(ml/min/1.73m2) I CKD with normal GFR but other renal damage (e.g. haematuria, proteinuria) > 90 II Mild CKD and other kidney damage 60-89 III Moderate CKD 30-59 IV Severe CKD 15-29 V Established ESRF < 15 or on Renal ReplacementTherapy 2. CLINICAL ASSESSMENT OF THE RENAL clinical tests. (Measures such as urine output FUNCTION correlate only poorly with perioperative renal function) (Table-2) A simple clinical assessment involves a set of Table2. Different parameters to assess clinical status Parameter Assessment Serum Creatinine: GFR should be assessed BUN Not ideal because influenced by dehydration and postoperative catabolic states Urine output (<400 may reflect hypovolaemia or impending “prerenal” renal failure; perioperative renal mL urine/24 hr) failure often develops in the absence of oliguria Urine specific gravity: >1.018 implies preserved renal concentrating ability Urinalysis and urine Inspection for cloudiness, color, odors characteristics BUN = blood urea nitrogen; GFR = glomerular filtration rate. 3. PERIOPERATIVE NEPHROLOGY  Prerenal azotemia is an increase in blood urea nitrogen associated with renal 3.1. Acute Kidney Conditions hypoperfusion or ischemia that has not yet It can be a result of many underlying conditions caused renal parenchymal damage. like:  Intrinsic AKI includes injury caused by  Acute kidney injury (AKI) is the preferred ischemia, nephrotoxins, and renal term for an acute deterioration in renal parenchymal diseases. function. It is associated with a decline in  Postrenal AKI (Obstructive Uropathy). glomerular filtration and results in an Downstream obstruction of the urinary inability of the kidneys to excrete collecting system is the least common nitrogenous and other wastes. AKI pathway to established AKI, accounting for frequently occurs in the setting of critical <5% of cases. illness with multiple organ failure, and the mortality rate is alarmingly high (≤90%).  Nephrotoxins and Perioperative AKI (Table-3) Table3. Types of Nephrotoxins Exogenous Endogenous Antibiotics(aminoglycosides, cephalosporins, Calcium (hypercalcemia) amphotericin B, sulfonamide, tetracyclines, Uric acid (hyperuricemia and hyperuricemia) vancomycin) Hemoglobin (hemolysis) Myoglobin (rhabdomyolysis) Anesthetic agents Bilirubin (obstructive jaundice) (methoxyflurane, enflurane) Oxalate crystals NSAIDs (aspirin, ibuprofen, naproxen, Ketorolac, Paraproteins indomethacin) Chemotherapeutic immunosuppressive agents (cisplatinum, cyclosporin A, methotrexate, mitomycin, nitrosoureas, tacrolimus) Contrast media 3.2. Chronic Kidney Disease (CKD)  The uremic syndrome represents an extreme form of CRF, which occurs as the surviving These patients usually have GFRs below 25% of nephron population and GFR decrease normal. Patients with decreased renal reserve below 10% of normal. It results in an are often asymptomatic and frequently may not inability of the kidneys to perform their two have elevated blood levels of creatinine or urea. major functions, regulation of the volume (ECF) and excretion of waste products. ARC Journal of Anesthesiology Page |10 Anesthesia Consideration for Renal Disease

 Water balance in ESRD becomes difficult to with anti-hypertensives, antibiotic coverage manage due to the decreased number of for urinary infections. Routine transfusion is functioning nephrons. This results in failure not recommended in chronic kidney disease both to conserve water and to excrete excess and may predispose to CHF. Electrolytes water. Such patients often require frequent should be corrected appropriately and or continuous dialysis. dialysis may be needed in severe renal failure. Premedicants may be necessary and  Life-threatening hyperkalemia may occur in anatacids prophylaxis may be considered. patients with CKD because of slower-than- normal potassium clearance. Derangements 5. PHARMACOLOGY OF DRUG IN RENAL in calcium, magnesium, and phosphorus DISEASE metabolism are also commonly seen in  Termination of drug action is mediated via patients with CKD. redistribution and metabolism, and is not  Metabolic acidosis occurs in two forms in dependent on renal excretion. Metabolism ESRD (hyperchloremic, normal anion gap leads to inactive form of parent drug and are acidosis and a high anion gap acidosis water soluble, therefore is excreted in urine. caused by an inability to excrete titratable Accumulation of these products due to acids) impaired renal excretion is not harmful. In patients with CKD, the effect of altered 4. PRE-OPERATIVE ASSESSMENT clearance, the production and accumulation  Routine anesthetic assessment along with of active metabolites, and the risk of special attention to renal functions is made. aggravating pre-existing kidney disease on  Hypertension is commonly seen in chronic drug administration must be considered. renal failure, because of renin angiotensin  Dose adjustment is not usually necessary pathway. Accelerated ischemic heart disease until the GFR is <50 ml/min/1.73 m2 and peripheral vascular disease are the consequences of the same. Pharmacokinetics  Proteinuria and hypoalbuminemia  Absorption – affected by delayed gastric predispose to oedema. Pericarditis, emptying autonomic and peripheral neuropathy is also commonly seen in chronic kidney disease.  Distribution – volume of distribution is increased or decreased depending on total  Urinalysis is a cheap, readily available, and body water, Protein binding & time since informative laboratory test. Proteinuria greater than 150 mg/day indicates severe last dialysis glomerular damage and glycosuria is  Elimination – prolonged half life for drugs indicative of diabetes mellitus. with renal elimination, e.g. Vecuronium  A complete blood count may reveal anemia 5.1. Local Anaesthetics (LA) of normocytic normochromic type of anemia, causes of the same include  L.A. has two plasma protein binding sites: a excessive hematuria, reduced production of high affinity, low capacity site on AAG (α1- erythropoietin by failing kidneys. acid glycoprotein) and a low affinity, high  Serum electrolytes although may remain capacity site on albumin. normal until severe renal disease should be  The albumin binding site becomes measured. increasingly important as the plasma  Determination of arterial blood gases may concentration of the local anaesthetic reveal metabolic acidosis in severe renal increases. failure due to impaired excretion of acid by the failing kidneys  Metabolic acidosis increases the percentage of unbound drug and this effect is more  Chest X ray and ECG may be required pronounced with bupivacaine. depending upon chronicity of disease and associated comorbidities.  Maximum dose to be decreased by 25% due  Patients should be optimized in preoperative to decreased protein binding and lower CNS period, hypertension should be managed seizure threshold in ESRD. ARC Journal of Anesthesiology Page |11 Anesthesia Consideration for Renal Disease

5.2. Inhalation Agents  All inhalation agents cause transient reversible ↓ of GFR, Renal blood flow,  “All inhalation agents are bio-transformed Urine output and renal auto to non-volatile products of metabolism regulation(Table-4) which are eliminated by kidney, but reversal of CNS effect depends upon pulmonary excretion”. Table4.Types of Inhalational agents with nephrotoxic potential Inhalation Agents Halothane Inorganic fluoride levels are less:1-2 μM/L No Nephrotoxicity Isoflurane Inorganic fluoride levels are less: 3-5 μM/L No Nephrotoxicity Desflurane Inorganic fluoride levels are very less, <1 μM/L after 1MAC-hr; No Nephrotoxicity highly stable & resists degradation by soda-lime & liver Sevoflurane Inorganic fluoride levels are less but not stable , 50 μM/L Compound A is prolonged use; degraded by soda-lime to compound A & nephrotoxic undergoes liver metabolism Enflurane Bio transformed to inorganic fluoride levels after prolonged use (> Nephrotoxic after 4hrs) prolonged use Methoxyflurane Bio transformed to high inorganic fluoride levels Highly nephrotoxic 5.3. Intravenous agents metabolized by liver and their excretion is not renal dependent. (Table-5) The induction agents of choice in renal disease are Propofol and Etomidate as they are Table5. Types of intravenous agents with nephrotoxic potential Thiopentone CNS effect reversed by redistribution & hepatic Metabol. unchanged , metabolism, also 80% protein bound, ↓albumin in Rate of admin. should be slow uremia ↑ free drug, more free un-ionised drug in Used in ↓ dose acidosis, also ↑ Vd (↓ protein binding) Propofol ↑ Vd but clearance & t unaltered, Metabolized by No adverse effect, time taken to 1/2 liver awake after infusion ↓ Etomidate Metabolised by liver, partial renal excretion No adverse effect Benzodiazepines Metabolised in liver & excreted by kidney, Longer ↑ Interval or ↓ dose (BZD) acting BZD accumulate, ↑ duration of action Ketamine Pharmacokinetics minimally changed Used in↓ dose Hepatic metabolites may depend on renal excretion and can potentially accumulate ↑ Increased; ↓ decreased; Vd volume of distribution 5.4. Muscle Relaxants produce neuromuscular blockade but due to reduced metabolism and excretion of drugs, The increased Volume of distribution in renal maintenance dose is decreased under disease necessitates the larger initial dose to neuromuscular monitoring (Table-6). Table6. Types of muscle relaxants with their nephrotoxic potential Succinylcholine Metabolised by psedocholinesterase to non toxic products Longer block in ESRD & which are excreted by kidney, ↑ duration in ESRD, also uremia,Cautiously used in ↓psedocholinesterase in uremia, Associated with rapid hyperkalemia transient ↑K⁺ (0.5mEq/L) Atracurium Degraded by enzymatic ester hydrolysis & non enzymatic Not dependent on renal alkaline degradation (Hoffmann elimination) to inactive elimination products 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 ↑Vd, 30% renal elimination, No change in clearance Prolonged duration Pancuronium 40-50% renal excretion, partly via less active 3-OH Prolonged duration pancuronium- renal excretion ↑ Increased; ↓ decreased; Vd volume of distribution

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5.5. Opioids excreted by the kidneys. Uraemia is associated with a lowered seizure threshold,  Opioids have no direct toxic effects on the and tramadol may be epileptogenic in these kidney (Table-7). circumstances.  They do, however, have an antidiuretic effect, and they may cause urinary retention.  Codeine and dihydrocodeine are also best avoided as their elimination half-life is  Tramadol: 30 % of tramadol is excreted significantly prolonged, and conventional unchanged in the urine. O-Demethyl doses have resulted in central nervous tramadol is an active metabolite which is system depression. Table7. Different Types of opioids agents with their nephrotoxic potential Opioids Morphine Conjugated to M-3-G, M-6-G,active Active metabolite has renal Dose adjustment metabolite, respiratory depression elimination, 40% conjugation required occurs in kidney Meperidine Normeperidine (main metabolite), Active metabolite has renal Dose adjustment (Pethidine) CNS toxicity elimination required Fentanyl ↓ Plasma protein binding,↑ free drug Clearance not altered (7% renal safe metabolism) Sufentanil ↓ Plasma protein binding,↑ free drug Clearance not altered safe Alfentanil ↓ Initial vol of distribution,↑ free drug Clearance not altered safe Remifentanil No change (ester hydrolysis ) Clearance not altered safe 6. ANESTHESIA 6.3. Fluid balance 6.1. Intra-operative  Patients may be dehydrated as they are given bowel preparation and may be on  General anesthesia with positive pressure dialysis, particularly in old age individuals. ventilation using muscle relaxation is recommended for open or laparoscopic  Appropriate fluid resuscitation is required in renal surgery. patients with signs and symptoms of dehydration so as to avoid sudden  Endotracheal intubation is used as there is hypotension at induction. increase in abdominal pressure owing to positioning of the patient and laparoscopic  Crystalloids are used for maintenance and surgery third space losses. Potassium containing fluids are avoided in patients with impaired  Rapid sequence intubation is preferred in renal function to avoid hyperkalemia. patients with gastropathy owing to chronic Colloids and packed red blood cells are renal failure. Induction of anesthesia may be reserved for blood loss replacement. achieved with intravenous and inhalational agents. Maintenance of anesthesia is  Aim of urine output should be 0.5-1 ml/kg/h achieved with inhalational agents. in patients with normal renal function. Dilaysis may be reserved in post operative  Atracurium is the preferred muscle relaxant period if there is fluid overload or chances as it is metabolized by Hoffman of patients going into overload. degradation. 6.4. Renal Protection  Large bore intravenous line is required as there may be sudden risk of bleeding. Limb  Various measures can be taken to protect with arteriovenous fistula must not be used kidney function in ongoing surgery. for intravenous infusions. Although surgery is a major factor, other contributory factors should also be avoided, 6.2. Monitoring which include dehydration, sepsis,  Routine standard monitoring is must. hypotension and nephrotoxic drugs Patients with end stage disease may require  Administration of fluids, dopamine, central venous pressure monitored fluid diuretics, calcium channel blockers, and administration. Temperature monitoring is angiotensin coverting enzyme inhibitors required as renal surgery may take many may be required to protect from renal hours. Warm intravenous fluids, warming damage. However there are conflicting blanket may be used. ARC Journal of Anesthesiology Page |13 Anesthesia Consideration for Renal Disease

evidence if any of these interventions is imperative that the anesthesiologists dealing protect kidney from damage. with such patients not only understand the management of these patients but also intervene 6.5. Post-Operative Pain Relief to prevent further renal injury during the There can be significant pain especially in open perioperative period. approach to kidney. Multimodal analgesia is REFERENCES required for early mobilization and to reduce incidence of post-operative pulmonary [1] Malhotra V and Diwan S. Anesthesia for the complications. Epidural analgesia should be a Renal and Genitourinary Systems. In: Miller norm unless contraindicated. Regional analgesia RD (Ed) Anesthesia. (5th Ed) Chapter 53; pg is contraindicated in presence of coagulopathy, 1934-1959. Churchill Livingstone, thrombocytopenia, anticoagulation, or recent Philadelphia. hemodialysis. Fentanyl and other short acting [2] Butterworth JF, Mackey DC, Wasnick JD. opioids are useful as they are largely Morgan and Mikhail’s Clinical th metabolized in liver. Non-steroidal anti- Anaesthesiology 5 Edition. Ch 29 pg 631 – inflammatory drugs are contra indicated because 652 (Renal Physiology and Anaesthesia) &Ch 30 pg 653 – 670 (Anaesthesia for patients with of their nephrotoxic potential. Paracetamol is a kidney disease) 2013 The McGraw Hill safe drug and is a good adjuvant analgesic. Companies, Inc. SUMMARY [3] Eilers H, Liu KD, Gruber A, Niemann CU. Patients with renal impairment or insufficiency Chronic kidney disease: implications for the are a challenge to attending anesthesiologists. perioperative period. Minerva Anestesiologica Adequate fluid of management, maintenance of 2010; 76:725 – 736. normovolumia, and avoidance of both [4] Wallace K. Renal Physiology. Update in hypotension and hypertension is required for Anaesthesia. successful prevention of further renal damage. It

Citation: Bhavna Gupta, Lalit Gupta. Anesthesia Consideration for Renal Disease. ARC Journal of Anesthesiology. 2018;3(1):9-14. DOI: dx.doi.org/10.20431/2455-9792.0301003. Copyright: © 2018 Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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