Ebook Coté and Lerman''s a practice of anesthesia for infants and children (6/E): Part 2

(BQ) Part 2 book “Coté and Lerman''s a practice of anesthesia for infants and children” has contents: Plastic and reconstructive surgery, burn injuries, cardiopulmonary resuscitation, malignant hyperthermia, regional anesthesia, ultrasound-guided regional anesthesia, chronic pain, anesthesia outside the operating room,… and other conetnts.

Acute Renal Failure and Acute Kidney Injury

Chronic Renal Failure

Preoperative Preparation of the Child With Renal Dysfunction

Preoperative Laboratory Evaluation

Postoperative Concerns

THE ANESTHESIA PRACTITIONER IS OFTEN FACED with a child

who has acute kidney injury (AKI) or renal failure Renal disease requiresthe practitioner to be vigilant about fluid homeostasis, acid-base balance,electrolyte management, choice of anesthetics, and potentialcomplications This requires a thorough understanding of the excretoryand fluid homeostatic functions of the kidney, particularly in the neonateand younger child If not managed assiduously, perioperative renaldysfunction can deteriorate into renal failure or multiorgan systemfailure resulting in significant morbidity or mortality The anesthesiaprovider must understand renal physiology, appropriate preoperativepreparation, intraoperative management, and postoperative care of thechild with renal disease

Renal Physiology

The basic functions of the kidney are to maintain fluid and electrolytehomeostasis and metabolism The first step in this tightly controlledprocess is the production of the glomerular filtrate from the renal plasma.The glomerular filtration rate (GFR) depends on renal blood flow (RBF),which depends on the systolic blood pressure and circulating bloodvolume The kidneys are the best perfused organs per gram of weight inthe body They receive 20% to 30% of the cardiac output maintained over

a wide range of blood pressures through changes in renal vascularresistance Numerous hormones play a role in this autoregulation,including vasodilators (i.e., prostaglandins E and I2, dopamine, and nitricoxide) and vasoconstrictors (i.e., angiotensin II, thromboxane, adrenergicstimulation, and endothelin) Congestive heart failure and volumecontraction severely limit the ability of the kidney to maintainautoregulation

When adjusted for body surface area (BSA) or scaled using allometrictheory (see Chapter 7), both RBF and GFR double in the first 2 weeks ofpostnatal life and both continue to increase steadily, reaching adultvalues by 2 years of age (see Figs 7.11 and 7.12).1 , 2 The increases in RBFover time parallel similar increases in cardiac output and decreases inrenal vascular resistance The initial GFR and the rate of increase duringthe first few years correlate with the neonate's postmenstrual age at birth

For example, the GFR (corrected using BSA or allometry) of a neonateborn at 28 weeks gestation is one-half of that of a full-term infant (see

Figs 7.11 and 7.12).3 GFR may be estimated from the serum creatinineconcentration and the height of the child according to the followingformula4,5:

In the equation, k is a constant that varies with age; 0.413 for infants,

0.55 for children, and 0.7 for adolescent boys The serum creatinineconcentration, especially in the first days of life, reflects the maternalserum creatinine concentration and therefore cannot be used to predictneonatal renal function until at least 2 days after birth.6

Fluids and Electrolytes

The kidney regulates the total body sodium balance and maintainsnormal extracellular and circulating volumes.7 The adult kidney filters25,000 mEq of sodium per day, but it excretes less than 1% throughextremely efficient resorption mechanisms along the nephron Theproximal tubule resorbs 50% to 70%, the ascending limb of the loop ofHenle resorbs about 25%, and the distal nephron accounts for 10% of thefiltered sodium load Several hormones, including renin, angiotensin II,aldosterone, and atrial natriuretic peptide (ANP), and changes incirculating blood volume contribute to maintaining the sodium balance.8Serum osmolality is tightly regulated through changes in argininevasopressin (AVP) release and thirst.9 11 AVP, also called antidiuretic hormone, is synthesized in the hypothalamus and stored in the posterior

pituitary, where it is released in response to an increasing plasmaosmolality AVP is also released in response to decreases in thecirculating blood volume and hypotension, including responses tonausea, vomiting, opioids, inflammation, and surgery AVP binds toreceptors in the collecting duct, increasing the permeability of the tubules

to water and leading to increased water resorption and concentratedurine Neonates are much less able to conserve or excrete watercompared with older children, rendering the fluid management andvolume issues important tasks for the anesthesiologist in this young agegroup.12

The regulation of serum potassium is managed by the kidney and

depends on the concentration of plasma aldosterone Aldosterone binds

to receptors on cells in the distal nephron, increasing the secretion ofpotassium in the urine Neonates are much less efficient at excretingpotassium loads compared with adults, and the normal range of serumpotassium concentrations is therefore greater in neonates; Table 28.1

provides the normal values.13 Potassium regulation is affected by theacid-base status; excretion of potassium increases in the presence ofalkalosis and decreases in the presence of acidosis Causes ofhyperkalemia and hypokalemia are presented in Tables 28.2 and 28.3,respectively

TABLE 28.1

Normal Values of Serum Potassium

Age Serum Potassium Range (mEq/L)

Nonsteroidal antiinflammatory drugs

Angiotensin-converting enzyme inhibitors

Anorexia nervosa

Acid-Base Balance

The kidney is involved in the regulation of acid-base balance and theresponse to the stress of illness The kidney reclaims virtually all of thefiltered bicarbonate in the proximal tubule and regenerates bicarbonate(HCO3−) lost in the neutralization of acid generated by the normalcombustion of food, especially protein, and the formation of bone Newbicarbonate is the product of cells in the distal nephron that decomposethe carbonic acid (H2CO3) formed from water (H2O) and carbon dioxide(CO2) by carbonic anhydrase The protons (H+) that are generated fromthis process are pumped into the lumen of the collecting duct, where theycombine with hydrogen phosphate (HPO42−) or ammonia (NH3)generated by the catabolism of amino acids, mainly glutamine, in thetubule cells

Infants, especially neonates, maintain a slightly acidotic blood (pH =7.37) and decreased plasma bicarbonate concentration (22 mEq/L)compared with older children and adults (pH = 7.39; plasma bicarbonate

= 24 to 28 mEq/L).14 The reduced plasma concentration of HCO3− is theresult of a reduced threshold or the plasma concentration at whichHCO3− is incompletely resorbed by the kidney Neonates maintain acid-base homeostasis but are limited in their ability to respond to an acidload.15 This is especially true for preterm infants

Disease States

The causes of and differences in renal diseases between children andadults are substantive Depending on the cause of the renal disease,management may be different Adult renal disease usually results fromlong-standing diabetes mellitus or hypertension with an associatedcompromise in cardiovascular function Children may also have renalfailure owing to diseases such as sickle cell disease or systemic lupuserythematosus, but cardiovascular function is far less commonlycompromised

Acute Renal Failure and Acute Kidney Injury

Acute renal failure (ARF) or acute renal insufficiency is defined as anabrupt deterioration in the ability of the kidneys to clear nitrogenouswastes, such as urea and creatinine Concomitantly, there is a loss ofability to excrete other solutes and maintain a normal water balance Thisleads to the clinical presentation of acute renal insufficiency: edema,hypertension, hyperkalemia, and uremia

Acute kidney injury (AKI) has almost replaced the traditional term acute renal failure (ARF), which was used in reference to the subset of patients

who had an acute need for dialysis With the recognition that evenmodest increases in serum creatinine are associated with a dramaticincrease in mortality, the clinical spectrum of acute decline in GFR isbroader Minor deterioration in GFR and kidney injury are captured in aworking clinical definition of kidney damage that allows early detectionand intervention and uses AKI in place of ARF The term ARF ispreferably restricted to those with AKI who also require renalreplacement therapy.16 The prognosis of AKI is assessed in part by theuse of the RIFLE criteria, which include three severity categories (i.e.,

Risk, Injury, and Failure) and two clinical outcome categories (Loss and End-stage renal disease) (Table 28.4)

TABLE 28.4

RIFLE Classification of Renal Failure and Kidney Injury

RIFLE

Factors GFR Criteria Urine Output Criteria

Risk Increased Cr × 1.5 or decreased GFR >25% UOP <0.5 mL/kg per hour > 6

hours

High sensitivity Injury Increased Cr × 2 or GFR decrease >50% UOP <0.5 mL/kg per hour > 12

hours Failure Increased Cr × 3 or GFR decrease of 75%

or Cr ≥4 mg/dL Acute rise ≥0.5 mg/dL

UOP <0.3 mL/kg per hour >

24 hours or Anuria > 12 hours Loss Persistent ARF: complete loss of kidney function > 4 weeks High

specificity ESKD End-stage kidney disease (> 3 months)

ARF, acute renal failure; Cr, creatinine; ESKD, end-stage kidney disease; GFR, glomerular filtration rate; RIFLE, Risk of renal dysfunction, Injury to the kidney,

Failure of kidney function, Loss of kidney function, and End-stage kidney disease;

UOP, urine output.

Modified from Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P Acute Dialysis Quality Initiative Workgroup Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality

Initiative (ADQI) Group Crit Care 2004;8:R204–R212.

The term ARF has often been incorrectly used interchangeably with

acute tubular necrosis (ATN), which usually refers to a rapid deterioration

in renal function occurring minutes to days after an ischemic ornephrotoxic event Although acute tubular necrosis is an important cause

of ARF, it is not the sole cause, and the terms are not synonymous Forthe purposes of this chapter, AKI refers to the disease formerly calledARF

Etiology and Pathophysiology

AKI is often multifactorial in origin or the result of several distinctinsults To treat AKI, it is important to understand its causes andpathophysiology The etiologies of AKI are varied, but can be broadlyclassified as follows (Table 28.5):

TABLE 28.5

Causes of Acute Renal Failure

Prerenal Failure Renal Failure Postrenal Failure

Membranoproliferative glomerulonephritis Rapidly progressive glomerulonephritis Glomerulonephritis due

to systemic disease (e.g., HUS, DIC, SLE)

Obstruction Intrinsic (papillary necrosis due to diabetes, sickle cell disease, or analgesic nephropathy) Intrarenal abnormalities, ureteral obstruction, obstruction of the bladder or urethra

Extrinsic (tumor compression, lymphadenopathy)

Decreased effective blood flow

Low cardiac output

Cirrhosis

Nephrotic syndrome

Tubular disease ATN (ischemic, nephrotoxic) Intratubular obstruction (uric acid, oxalate) Renal hypoperfusion

Use of ACE inhibitors

NSAIDs

Hepatorenal syndrome

Cortical necrosis Gram-negative sepsis Hemorrhage

Shock Vascular occlusion

glomerulosclerosis Nephrocalcinosis Obstructive uropathy Hypertension

ACE, angiotensin-converting enzyme; ATN, acute tubular necrosis; DIC, disseminated intravascular coagulation; HUS, hemolytic uremic syndrome; NSAIDs, nonsteroidal antiinflammatory drugs; SLE, systemic lupus erythematosus.

■ Prerenal, implying poor renal perfusion as the cause

■ Renal, implying intrinsic renal disease or damage as the cause

■ Postrenal, implying an obstruction to the excretion of urine as the cause

Prerenal insults comprise the majority (up to 70%) of cases of AKI.They usually result from massive losses of extracellular fluid, such as ingastroenteritis, burns, hemorrhage, or excessive diuresis, as well as in

cardiac failure and sepsis The common feature of this condition isdiminished renal perfusion In response to the reduction in RBF, there is

a compensatory increase in afferent tone, which decreases the GFR andincreases the retention of salt and water The net effect of these events is adrastic reduction in urine volume, often leading to oliguria and/oranuria If the underlying problem is recognized early and treatedaggressively, progressive renal insufficiency may be averted.Nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme(ACE) inhibitors, and angiotensin receptor blockers can aggravateprerenal azotemia by further reducing glomerular capillary pressure andthe GFR.17

Parenchymal disease or injury accounts for 20% to 30% of the cases ofabrupt onset of AKI In infants, the common causes include birthasphyxia, sepsis, and cardiac surgery In older children, the importantcauses of AKI include trauma, sepsis, and hemolytic uremic syndrome.Prolonged prerenal azotemia may result in overt renal injury Similarly,intrarenal obstruction to blood flow from thrombi or vasculitis may causerenal failure Drugs such as aminoglycosides or amphotericin B or othernephrotoxins, including radiocontrast agents, may induce AKI throughtubular or interstitial injury as a result of allergic reactions, as can be seenwith penicillins Acute glomerulonephritis is another cause of AKI inchildren; rarely, pyelonephritis can lead to AKI

The remaining causes of AKI result from the obstruction to urine flow.These conditions account for less than 10% of all cases of AKI and mayinvolve obstruction of both kidneys Sudden anuria suggests a postrenalcause for the AKI The obstruction can occur within the collecting system

of the kidney (intrarenal), in the ureter, or in the urethra (extrarenal).Intrarenal obstruction may occur with the tumor lysis syndrome with thedeposition of uric acid crystals, from myoglobinuria, hemoglobinuria, orfrom medications such as acyclovir and cidofovir Extrarenal obstructioncan be caused by stones inspissated in the ureters or from externalcompression by lymph nodes or a tumor As with other forms of AKI,prompt recognition and appropriate intervention to relieve theobstruction may facilitate full recovery of renal function and obviate apermanent reduction in renal function

The exact pathophysiology of AKI remains unclear, but several factorshave been identified.18 In the initial phase of AKI, profound renovascular

vasoconstriction reduces GFR (Fig 28.1) Factors known to increase renalvasoconstriction include increased activity of the renin-angiotensin andthe adrenergic systems and endothelial dysfunction with increasedendothelin release and decreased nitric oxide synthesis However,therapeutic interventions to vasodilate the intrarenal vasculature, such asprostaglandin and dopamine infusions, ACE inhibitors, calcium channelblockers, and endothelin receptor antagonists, have not significantlyreversed established AKI.19

of acute renal failure

Another factor in the pathogenesis of AKI is renal tubule cell injury,the direct result of a nephrotoxic agent or from an ischemic insult (Fig.28.2) Cellular injury leads to sloughing of the brush border, swelling,mitochondrial condensation, disruption of cellular architecture, and loss

of adhesion to the basement membrane with shedding of cells into thetubular lumen.20 These changes, which occur within minutes of anischemic event, contribute to the decreased GFR by obstructing thelumen of the tubule.21 These cellular changes allow the filtrate to leakback into the peritubular blood, reducing the excretion of solutes and the

effective GFR.

nephron in the pathogenesis of acute renal failure ATP,

adenosine triphosphate

Some of the cellular derangements in AKI, such as a reduction in ATPconcentrations,21 cell membrane injury by reactive oxygen molecules,22and increased intracellular calcium concentrations from changes inmembrane phospholipid metabolism, lead to cell death Reactive oxygenmolecules also stimulate the production of cytokines and chemokinesthat play a role in cell injury and vasoconstriction

Neutrophils that are recruited during reperfusion injury after renalischemia mediate parenchymal renal damage.23 Reperfusion injuryincreases intracellular adhesion molecule 1 (ICAM-1) on endothelial cellspromoting the adhesion of circulating neutrophils and their eventualinfiltration into the parenchyma Neutrophils then release reactiveoxygen molecules, elastases, proteases, and other enzymes that lead tofurther tissue injury

Diagnostic Procedures

A thorough history and physical examination can yield important insightinto the likely causes of AKI The initial laboratory assessment of a childwith AKI should include the measurement of serum urea, creatinine,electrolytes, and a urinalysis Prerenal azotemia is typically associatedwith a ratio of blood urea nitrogen (BUN) to creatinine that exceeds 20 Incases of renal parenchymal dysfunction, this ratio is closer to 10.Hematuria and proteinuria are consistently present in AKI, independent

of the cause, although the presence of cellular casts, especially red bloodcell casts, in the urinary sediment is suggestive of glomerulonephritis.Granular casts are associated with prerenal azotemia

One test to distinguish prerenal azotemia from established renal failurefrom ischemia or nephrotoxins is the fractional excretion of sodium(FENa) The FENa is calculated using the following equation:

UNa and SNa are urine and serum sodium concentrations, and UCr and

SCr are the urine and serum creatinine concentrations, respectively Inprerenal azotemia, the FENa is usually less than 1% for adults andchildren and less than 2.5% for infants In established AKI from ischemiaand nephrotoxins, but not acute glomerulonephritis, the FENa usuallyexceeds 1% Administration of diuretics may confound the interpretation

of this test

The initial radiologic assessment of children with AKI isultrasonography Renal ultrasound does not depend on renal functionand can define the renal anatomy, changes in parenchymal density, andpossible outlet obstruction by demonstrating dilation of the urinary tract.Doppler interrogation of the renal vessels provides information onvascular flow Further radiographic studies, such as voidingcystourethrography, nuclear renal flow scanning, dynamic functionalMRI, and abdominal computed tomography (CT), may be indicated inselect children and conditions

Therapeutic Interventions

Therapeutic interventions in children with AKI should be aimed at the

underlying cause and at improving renal function and urine flow.Children with AKI caused by hypovolemia should be fluid resuscitatedwith at least 20 mL/kg over 30 to 60 minutes with normal saline solution

or a balanced salt solution For children with significant hypotension, analternative choice is a colloid-containing solution Children with oliguriacaused by hypovolemia usually respond within 4 to 6 hours withincreased urine output Anecdotal reports have supported the use of low-dose dopamine in AKI A recent clinical trial has demonstrated benefitfrom dopamine in improving urine output in very low–birth-weightneonates.24

Diuretics have been commonly used to treat oliguric AKI There areseveral theoretical reasons why mannitol, furosemide, and other loopdiuretics may ameliorate AKI First, diuretics may convert oliguric AKI

to nonoliguric AKI Second, loop diuretics decrease energy-driventransport in the loop of Henle, and this may protect cells in regions ofhypoperfusion However, neither mannitol nor loop diuretics canpredictably convert an oliguric patient with AKI to a polyuric patient.Diuretics have not been shown in clinical studies to influence renalrecovery, need for dialysis, or survival in patients with AKI.25 , 26 Diureticsshould be used only after the circulating volume has been adequatelyrestored and should be stopped if there is no early response

Dopamine has been widely used to prevent and manage AKI In lowdoses (0.5–2.0 µg/kg per minute), dopamine increases renal plasma flow,GFR, and renal sodium excretion by activating dopaminergic receptors.Infusion rates in excess of 3 µg/kg per minute stimulate α-adrenergicreceptors on systemic arterial resistance vasculature, causingvasoconstriction; cardiac β1-adrenergic receptors, increasing cardiaccontractility, heart rate, and cardiac index; and β2-adrenergic receptors

on systemic arterial resistance vasculature, causing vasodilatation In ameta-analysis of 24 studies and 854 adult patients, dopamine did notprevent renal failure, alter the need for dialysis, or change the mortalityrate In a randomized clinical trial of low-dose dopamine in 328 criticallyill adult patients, dopamine did not change the duration or severity ofthe renal failure, need for dialysis, or mortality.27 From these data, theroutine use of low-dose dopamine in patients with AKI cannot besupported

Several other agents that were useful in experimental models of AKI

have been investigated but have not shown clinical success ANPincreases GFR in animal models of AKI by increasing renal perfusionpressure and sodium excretion An initial study demonstrated somebenefit with ANP in patients with AKI,28 especially in those with oliguricAKI,29 although a subsequent study of 222 adult patients with oliguricAKI failed to detect a difference between patients treated with ANP andplacebo in terms of the need for dialysis or mortality.30 Insulin-likegrowth factor 1 has been beneficial in animal models of AKI, presumably

by potentiating cell regeneration However, in a multicenter, controlled trial in adult patients with AKI, insulin-like growth factor 1failed to speed the recovery, decrease the need for dialysis, or altermortality.31 Thyroxine abbreviates the course of experimental AKI buthad no effect on the duration of renal failure and actually increasedmortality threefold (by suppression of thyroid-stimulating hormone).32

placebo-In patients with severe AKI, renal replacement therapy throughdialysis is life sustaining The indications for initiation of dialytic therapyare persistent hyperkalemia, volume overload refractory to diuretics,severe metabolic acidosis, and overt signs and symptoms of uremia such

as pericarditis and encephalopathy Many nephrologists recommenddialysis if the BUN value approaches 100 mg/dL or even earlier,especially in the oliguric patient, although this has not proved to alteroutcome A retrospective study that compared early (BUN <60 mg/dL)versus late (BUN >60 mg/dL) initiation of dialysis in adult patientssuggested that early initiation improved survival.33 However, the timing

of the initiation of dialysis remains an unresolved question

Three strategies are available to replace renal function in critically illchildren and adults: hemodialysis, peritoneal dialysis, and a variation ofcontinuous replacement therapies, such as continuous venovenoushemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD),and continuous venovenous hemodiafiltration (CVVHDF) None of thesestrategies has been proven superior to the others However, in theindividual child, one strategy may be more practical than the others.Hemodialysis is technically more difficult than peritoneal dialysis in aninfant and hemodynamically unstable children Continuous replacementtherapies appear to cause less hemodynamic instability compared withhemodialysis and offer more predictable solute and fluid removal thanperitoneal dialysis Hemodialysis and continuous replacement therapiesrequire large-bore vascular access to achieve the large blood flows that

are necessary to support these strategies.

Although these three strategies differ technically, they share similarprinciples (Fig 28.3) All three strategies remove nitrogenous wastes (i.e.,urea), excess fluid, and excess solutes, especially potassium This isachieved by circulating the child's blood over a semipermeablemembrane that separates the blood from a salt solution (i.e., dialysate) onthe contralateral surface The movement of solutes across the membranesoccurs by diffusion (i.e., solutes move across the membrane along theirconcentration gradients) and ultrafiltration (i.e., osmotic or hydrostaticpressures) The rate of removal of water and solute waste depends on thecharacteristics of the membrane (i.e., pore size and selectivity), diffusion,and ultrafiltration.34

moves from the blood to the dialysate (broken arrows) in

response to a concentration gradient (i.e., diffusion) The

obligate passive movement of water (blue circles)

attempts to maintain appropriate osmolarity This flux of

solute and water (i.e., ultrafiltration) may be enhanced by

increased osmotic pressure (i.e., glucose in peritoneal

dialysis fluid) or by increased hydrostatic pressure, which

is created mechanically as transmembrane pressure in

hemodialysis

The permeability characteristics and surface areas for the membranesare known for specific dialyzers used in hemodialysis and hemofiltration.The peritoneum serves as the dialysis membrane in peritoneal dialysisand remains physically unalterable, but changes in dialysate composition

and length of time the dialysate is exposed to the peritoneal membranechanges the amount of solute and water removed In all forms of renalreplacement therapy, the therapeutic prescription is individualized forthe child.

Hemodialysis

Hemodialysis is very effective for AKI, being the best modality for therapid removal of toxins, such as drug overdoses or other ingestions ormetabolic toxins resulting from poisoning or inborn errors Hemodialysis

is very efficient, reducing the BUN by 60% to 70%, normalizing theserum potassium concentration, and removing fluid equal to 5% to 10%

of the body weight within 3 to 4 hours To accomplish this, large-vesselvenous access is required to provide rapid blood flows (5-10 mL/kg perminute) In infants, this is achieved by inserting a double-lumen catheterinto the subclavian, internal jugular, or femoral vein In small infants,two single-lumen catheters placed in different sites may be necessary toaccess and return the blood Rarely, a single-lumen catheter may be usedfor both outflow and return of blood Modern hemodialysis machineshave microprocessors that can accurately measure the amount of fluidremoved and this should be summarized for the anesthesiologist

Hemodialysis usually requires systemic anticoagulation with heparin,the effectiveness of which can be monitored by the activated clotting time(ACT) Hemodialysis can be undertaken without an anticoagulant inchildren who are at significant risk for bleeding by using a rapid bloodflow rate and by frequently rinsing the blood circuit with saline.However, clotting commonly forms within the circuit with subsequentloss of the extracorporeal blood

In addition to the risk of bleeding, hemodialysis is associated withseveral other adverse effects, the most common of which is hypotension.This usually results from overly aggressive removal of fluid, although itcan also result from sepsis or the release of cytokines and autokines fromblood passing over the surface of the hemodialysis filter Muscle cramps,headache, nausea, and vomiting are also commonly reported A moreserious complication of hemodialysis is the disequilibrium syndrome that

is related to the rapid removal of solute from the bloodstream with slowequilibration with the tissues, particularly the brain This can causecerebral edema, manifested by headache, obtundation, seizures, or coma

The disequilibrium syndrome is usually reported in children undergoingdialysis for the first time This can be obviated by dialyzing for brief butfrequent sessions initially, especially if the BUN concentration isincreased substantially Infection of the dialysis catheter is anothercommon problem that can be minimized by using sterile central linetechniques.

Peritoneal Dialysis

Peritoneal dialysis has a long history as renal replacement therapy inchildren.35 It is relatively simple and easy to perform, even in smallinfants, and there is usually no hemodynamic instability Although not asefficient as hemodialysis, optimal results are obtained if it is performedcontinuously to control solute and water balance Peritoneal dialysisinvolves instilling dialysate fluid into the peritoneum for a set period andthen draining the fluid and replacing it with fresh dialysate This cyclingremoves waste products by diffusion and water by ultrafiltration as aconsequence of a high glucose concentration in the dialysate The efficacy

of peritoneal dialysis depends on the volume of dialysate instilled percycle and the number of cycles per day Most children with acute renalfailure are managed with 1- to 2-hour cycles of 5- to 30-mL/kg dwellvolumes Children with chronic renal failure are managed with greatercycle times and larger dwell volumes The amount of fluid removed can

be controlled by changing the concentration of the glucose in thedialysate Short-term peritoneal dialysis can be accomplished with anontunneled catheter, but should dialysis be required beyond 3 to 5 days,

a subcutaneously tunneled cuffed catheter is preferred to minimize therisk of peritonitis

The principal complications of peritoneal dialysis are infection andmechanical problems related to the catheter It is common to find poordrainage from the catheter, usually the result of fibrin occlusion of thecatheter or from omentum or bowel covering the inlet holes The cathetermay leak at its point of insertion Hernias, especially inguinal hernias inboys, may develop as a consequence of the increased abdominal pressurefrom the infused dialysate Mild hyponatremia may develop in infantsbecause of the relatively low sodium concentration (130 mEq/L) incommercial dialysate Less common but serious complications includebowel injury and intraabdominal hemorrhage from catheter insertion

and peritonitis.

Chronic Renal Failure

The loss of functioning renal mass results in a compensatory increase infiltration by the remaining renal tissue.36 For example, within the first 48hours after a unilateral nephrectomy, there is a demonstrable increase inthe GFR and evidence of contralateral renal hypertrophy By 2 to 4weeks, the GFR has returned to 80% of normal, and there is no clinicalevidence of renal dysfunction With the loss of 50% to 75% of renal mass,there is an increase in the residual function to 50% to 80% of normal andoften little evidence of clinical renal insufficiency When the residual

renal function decreases to 30% to 50% of normal, the term chronic renal insufficiency applies At this point, acute illness and other stress states

may result in acidosis, hyperkalemia, and dehydration It is only whenthe residual function decreases to less than 30% of normal that the term

chronic renal failure is used At this point, electrolyte abnormalities begin

to appear, and more importantly, there is limited ability of the kidney toadjust to perturbations in volume status and electrolyte concentrations

The term uremia refers to the symptoms of anorexia, nausea, lethargy,

and somnolence that develop as a result of chronic renal failure Uremiaultimately leads to death unless dialysis therapy or renal transplantation

is performed Initiating dialysis or transplanting a kidney is referred to asend-stage renal disease care

Chronic renal insufficiency and chronic renal failure are bothcategories within the larger schema of chronic kidney disease (CKD).Although the stages are defined by categorizing continuous measures offunction (i.e., GFR) and therefore are somewhat arbitrary, they doprovide a context for the evaluation and management of kidney disease.There are six stages of CKD:

Stage I: The GFR is normal (>90 mL/minute per 1.73 m2), but theremay be evidence of chronic renal disease, including an abnormalurinalysis, hypertension, or abnormal renal ultrasound

Stage II: A GFR of 60 to 89 mL/minute per 1.73 m2 indicates mildkidney damage and mild decrease in GFR

Stage III: A GFR of 30 to 59 mL/minute per 1.73 m2 is a moderatedecrease in the GFR

Stage IV: A GFR of 15 to 29 mL/minute per 1.73 m2 is a severedecrease in the GFR, often accompanied by electrolyte or metabolicderangements.

Stage V: A GFR <15 mL/minute per 1.73 m2 indicates kidney failurethat requires renal replacement therapy

Stage VI: Patients are undergoing dialysis or are transplant recipients

Despite losses of up to 90% of renal function, sodium homeostasisusually is well maintained in chronic renal failure With large decreases

in the GFR, the kidney maintains normal serum sodium by increasing the

FENa from less than 1% up to 25% to 30%, largely through decreases indistal tubular resorption Some of the hormonal factors associated withthis adaptation include aldosterone, ANP, and a poorly characterizednatriuretic hormone that inhibits Na+/K+-ATPase With chronic renalfailure, the kidney loses its ability to handle a wide range of sodiumintake, from 1 to 250 mEq/m2 per day Instead, the kidney may only beable to handle a narrow range of sodium intake of 50 to 100 mEq/m2 perday It may be possible to decrease this obligatory excretion of sodium to

5 to 20 mEq/m2 per day, although it may occur only after weeks ofdecreasing the sodium intake slowly Certain children with renal disease,especially those with obstructive uropathy or tubulointerstitial disease,may be unable to adjust to a decreased sodium intake and display a salt-losing nephropathy These children are prone to dehydration with saltrestriction and may need supplemental salt to ensure normal growth Inothers, a regular diet may lead to sodium retention, volume overload,and hypertension; sodium intake must be individualized to fit thelimitations of each child

Water balance is also affected by chronic renal failure There is anobligatory total osmolar excretion that limits the ability of the kidney toexcrete free water The concentrating ability of the kidney is affected,limiting its ability to make a maximally concentrated or dilute urine.These limitations may result in water retention and hyponatremia ordehydration if water is administered in amounts exceeding the kidney'scapabilities These limitations must be considered when treating childrenwith chronic renal failure, particularly before surgery when free access towater is restricted

In those with chronic renal failure, the serum potassium concentrationsusually remain normal until the GFR is less than 10% of normal

Potassium excretion normally occurs in the distal nephron However, inresponse to an increase in potassium intake or loss of renal mass, Na+/K+-ATPase increases in the remaining collecting tubules; this is responsible,

in part, for the augmented excretion of potassium per nephron In uremicanimals, potassium is excreted from the renal tubules sixfold faster than

in nonuremic animals and 1.5 times the filtered potassium load Partialadaptation can occur in the absence of aldosterone, but aldosterone plays

an important role in the maintenance of normal potassium homeostasis.This is demonstrated by the presence of hyperkalemia in children withhyporeninemic hypoaldosteronism or in those treated with thealdosterone antagonist spironolactone

Approximately 13% of dietary potassium is excreted via the colon Thiscan increase to 50% by the activation of colonic Na+/K+-ATPase viaaldosterone An additional mechanism that plays an essential role in theadaptation to an acute potassium load is the redistribution of potassiumfrom the extracellular to the intracellular compartment, which depends

on insulin, β-adrenergic catecholamines, aldosterone, and pH Despitethe presence of total body potassium depletion in uremia, the uptake ofpotassium into the cells is impaired This contributes to the intolerance to

an acute potassium load in uremia despite the ability to excrete apotassium load

Hyperkalemia is a major problem in chronic renal failure.37Hyperkalemia can result from an extrinsic potassium load, but it mayalso be caused by fasting or acidosis, in which case the source of thepotassium is the intracellular compartment This can be a particularproblem when a child has fasted before surgery and can be ameliorated

by an infusion of glucose and insulin Drugs that can cause hyperkalemia

in renal failure include spironolactone, β-adrenergic blockers, and ACEinhibitors When clinically significant hyperkalemia develops in a childwith chronic renal failure, the first-line therapy is to stabilize themyocardium with exogenous calcium and then to redistribute thepotassium into the intracellular compartment with insulin and glucose

To deliver the same dose of ionized calcium, the dose of calciumgluconate (in milligrams per kilogram) should be three times that ofcalcium chloride All doses of calcium are optimally delivered through acentral venous access line because calcium infusions are irritating toperipheral veins and can cause necrosis of the skin if extravasationoccurs More definitive correction of hyperkalemia is accomplished by

removing potassium from the body using dialysis or sodium polystyrenesulfonate (Kayexalate) At eight times the usual asthma dose, nebulizedalbuterol has been effective in redistributing potassium intracellularly,whereas sodium bicarbonate (NaHCO3) administration has not beeneffective (Table 28.6) In contrast, significant hypokalemia is unusual inthe absence of potassium restriction, alkalosis, or diuretic therapy.

Shifting of Potassium to Intracellular Space

Hyperventilation

Insulin and glucose Insulin: 0.10–0.3 unit/kg or

0.1 U/kg per hour infusion Glucose: D50 1–2 mL/kg or

D25 2–4 mL/kg IV or

D5 1–2 mL/kg per hour Albuterol Albuterol: 2.5–5 mg/mL nebulization

Decreasing Total Body Potassium

Sodium polystyrene sulfonate (Kayexalate) 1 g/kg up to 40 g every 4 hours PO or PR

Furosemide (diuretic) 0.5 mg/kg up to 40 mg

D, dextrose; IV, intravenous; PO, per os (oral); PR, per rectum (suppository).

Metabolic acidosis is common in those with chronic renal failure.38 Inmoderate renal insufficiency, the type of metabolic acidosis is a non–anion gap acidosis, but in severe renal insufficiency, the metabolicacidosis is an anion gap acidosis, because of the presence of excessphosphate, sulfate, and organic acids The primary cause of metabolicacidosis in chronic renal failure is the inability of the remaining proximalrenal tubules to increase ammonium formation to keep pace with the loss

of renal mass The kidney becomes unable to generate the 1 to 3 mEq/kgper day of new bicarbonate that is necessary to compensate for thebicarbonate lost to buffering endogenous acids Previous studies havesuggested a major role for decreased resorption of bicarbonate by theproximal renal tubule in chronic renal failure Although this may occur

in the presence of volume overload, severe secondaryhyperparathyroidism, and disorders such as Fanconi syndrome, it is not

a major cause of acidosis in chronic renal failure Except for severephosphate depletion, decreased excretion of phosphate as a titratableacid normally does not contribute to metabolic acidosis

One of the earliest manifestations of chronic renal failure is secondaryhyperparathyroidism.39 Secondary hyperparathyroidism, which resultsfrom inadequate formation of 1,25-(OH)2 vitamin D (i.e., 1,25-dihydroxyvitamin D3 or calcitriol), develops in moderate renalinsufficiency in the presence of normal serum concentrations of calciumand phosphorus As the renal insufficiency becomes more severe, overthypocalcemia and hyperphosphatemia often develop Hypocalcemia iscaused by decreased calcium absorption from the gastrointestinal tract as

a result of a true deficiency of 1,25-(OH)2 vitamin D Diminished release

of calcium from bone occurs as a result of resistance to the action ofparathyroid hormone Calcium and phosphate may be deposited in softtissues as a consequence of hyperphosphatemia

The kidney plays a key role in the maintenance of phosphatehomeostasis by regulating its excretion In the presence of a normal GFR,the kidney excretes 5% to 15% of the filtered load of phosphate, whereas

in chronic renal failure, the kidney can increase its fractional excretion ofphosphate to 60% to 80% Through this adaptation, the kidneys are able

to maintain a phosphate balance in chronic renal failure, but they do so at

an increased serum phosphate concentration More importantly, thefailing kidneys have no reserve with which to increase phosphateexcretion in response to a phosphate load In children with chronic renalfailure, a large phosphate load, such as can occur with the administration

of a phosphate-containing enema, can lead to life-threateninghyperphosphatemia and hypocalcemia

Hematologic Problems

One of the most common manifestations of chronic renal failure isanemia The anemia of chronic renal failure is the result of impairederythropoiesis, hemolysis, and bleeding Of these, impairederythropoiesis is most important and usually the result of a deficiency oferythropoietin production Erythropoietin is synthesized and secreted by

the peritubular cells in the renal cortex in response to decreased tissueoxygenation It acts on receptors on the erythroid burst-forming unitsand erythroid colony-forming units With loss of renal mass,erythropoietin secretion does not respond adequately to hypoxia, andanemia ensues Children with chronic renal failure are now treated withrecombinant erythropoietin (50–150 U/kg by intravenous [IV] injectionthree times per week) when their hematocrit decreases to less than30%.40 , 41 When the hematocrit increases to 36%, the dose is maintained atapproximately 75 U/kg with the same frequency Erythropoietin mayalso be administered subcutaneously only once weekly, obviating theneed for IV injections Doses of erythropoietin in excess of 150 U/kgincrease the hematocrit faster than smaller doses, but both therapies take

4 to 8 weeks to reach the target hematocrit of 33% to 36% Children whoare scheduled for erythropoietin therapy should begin oral iron, vitamin

C (a cofactor for iron absorption from the gastrointestinal tract), and folicacid 2 to 3 weeks in advance to ensure adequate iron and folic acid stores

to facilitate erythropoiesis The most common cause for failure oferythropoietin, and therefore erythropoiesis, is concurrent irondeficiency Current recommendations are aimed at maintaining serumferritin concentrations in excess of 250 ng/mL and a transferrin saturationgreater than 25% Other causes for the failure of erythropoietin toincrease or maintain the hematocrit are occult infections, hemolysis,aluminum overload, severe hyperparathyroidism, and occult bleeding.Complications of erythropoietin therapy include worsening ofhypertension and a possible increased incidence of thrombosis ofpolytetrafluoroethylene vascular grafts

The other major hematologic problem in chronic renal failure isbleeding This classic and lethal complication in children with terminaluremia results from platelet dysfunction in the presence of a normalcoagulation profile and normal platelet counts The best indicator ofplatelet dysfunction in children with chronic renal failure is a prolongedbleeding time The platelet dysfunction is the result of poorly describedabnormalities attributed to the uremic environment, rendering platelettransfusions ineffective Dialysis improves platelet dysfunction, as doesimprovement in the hematocrit with transfusions or erythropoietintherapy Preoperative IV desmopressin acetate (1-deamino-8-D-argininevasopressin, DDAVP) (0.3 µg/kg) improves the bleeding time in childrenwith uremia

Cardiovascular Complications

Hypertension is one of the most common complications of chronic renalfailure and contributes significantly to the morbidity and mortality ofthese children The cause is multifactorial and includes volume overloadand hormonal abnormalities, such as increased secretion of renin, thatresult from the underlying renal disorder In children who areundergoing dialysis, volume overload is the result of inadequate removal

of volume during dialysis The goal of ultrafiltration is to removesufficient salt and water to achieve the dry weight that is appropriate for

each child The dry weight is the weight at which the child has no signs of

volume overload but below which the child has hypotension The initialresponse to volume overload is to increase the cardiac output Later, thecardiac output returns to normal, but the peripheral resistance increasesbecause of peripheral vasoconstriction, resulting in hypertension Thesechildren may have no other signs of volume overload, such as edema,but with a reduction in total body salt and water content, the bloodpressure can be controlled with little or no antihypertensive medication

In other children, intrinsic renal abnormalities play a primary role inhypertension Oral antihypertensive agents are often effective incontrolling the severe refractory hypertension, although in some,bilateral nephrectomies may be required to control the hypertension Ofthe mechanisms that cause hypertension in these children, increasedrenin secretion is the best understood Renin activates the formation ofangiotensin I, which is then converted to angiotensin II, a powerfulvasoconstrictor Children with renin-dependent hypertension respondpoorly to control of blood pressure by salt and water removal alone butrespond well to ACE inhibitors such as captopril

Cardiovascular disease is the most common cause of death in patientsundergoing long-term dialysis, including children.42 Children withchronic renal failure can have abnormalities of the pericardium,myocardium, cardiac valves, and coronary arteries Pericarditis was onceconsidered a sign of the terminal phase of uremia, but it occurs in 15% ofchildren who are undergoing dialysis and can be symptomatic orclinically silent In uremic patients with pericarditis who are notundergoing dialysis, intensive dialysis often results in its resolutionwithin ~2 weeks Some children require surgical procedures such aspericardiocentesis, pericardial drainage with a catheter or through a

pericardial window, or pericardiectomy.

Left ventricular failure is also a common complication of chronic renalfailure In older patients, coronary artery disease may lead to myocardialdysfunction, severely limiting cardiac output Volume overload andhypertension, which increase preload and afterload, respectively, areimportant causes of heart failure With proper fluid management andantihypertensive medication, these abnormalities can be controlled.Anemia is another contributing factor that can be controlled with the use

of erythropoietin An array of metabolic abnormalities associated withchronic renal failure, such as secondary hyperparathyroidism, electrolyteand acid-base imbalances, and the accumulation of nonspecific uremictoxins, contribute to abnormal myocardial function

Causes of Chronic Renal Failure

The causes of chronic renal insufficiency and failure can be correlatedwith age (Table 28.7) The chronic renal failure that is commonlyencountered in early infancy results largely from congenital anomalies orperinatal asphyxia Later in childhood, renal failure may result fromdysplasia, or acquired lesions, whereas those affected in adolescence mayhave deterioration of function related to acquired disease, manifestation

of inherited disease, or secondary lesions resulting from other illnesses(e.g., systemic lupus erythematosus, sickle cell disease) or theirtreatments

TABLE 28.7

Causes of Chronic Renal Failure and Associated Syndromes

Infancy (Congenital

Anomalies) Childhood Adolescence

Prune-belly syndrome Dysplasia Focal segmental glomerulosclerosis Congenital obstruction Agenesis Membranoproliferative

glomerulonephritis Posterior urethral valves Autosomal dominant PKD Secondary glomerulonephritis Multicystic dysplasia Reflux nephropathy Systemic lupus erythematosus Agenesis Obstruction Sickle cell disease

Autosomal recessive PKD Focal segmental glomerulosclerosis HIV-associated nephropathy Reflux nephropathy Membranoproliferative

glomerulonephritis Diabetes mellitus

Vasculitis Hemolytic uremic syndrome Henoch-Schönlein purpura Interstitial nephritis Malignancy

HIV, human immunodeficiency virus; PKD, polycystic kidney disease.

Preoperative Preparation of the Child With Renal Dysfunction

Renal disease in children is a significant cause of perioperative morbidityand mortality and thus influences the approach to general anesthesia.43–45The preoperative preparation of these children depends largely on thestage of the renal dysfunction and the level of severity Whether the childhas CKD, AKI, has undergone a kidney transplant, or is susceptible to anintraoperative renal insult, the approach to the preoperative andperioperative anesthesia care will change

CKD is a multisystem disease that requires a thorough andcomprehensive preoperative assessment These children may be oliguricand at risk of fluid overload or polyuric and vulnerable to dehydration.Electrolyte and acid-base disturbances are predictably common.Alterations in compartment volumes and protein binding change drugpharmacokinetics Hypertension may be present owing to fluid overload,exacerbated by renin excretion from the failing kidney or from anautonomic hyperactivity common in CKD Typically these children have

a normocytic normochromic anemia (from reduced erythropoietin levels)and platelet dysfunction by uremia Ascites, common in end-stage renaldisease, increases the risk of aspiration and pulmonary atelectasis in theperioperative period Children may be encephalopathic secondary toincreased blood concentrations of urea and may have seizure disorders.Finally, the CKD may be part of a syndrome, with other importantimplications for anesthesia Therefore careful delineation of the type ofrenal disease and its comorbidities should be reviewed at the time of thepreoperative visit to anticipate potential problems during the anesthetic.Perioperative renal dysfunction may also occur in any child withnormal renal function who is subjected to perioperative insults AKI aftercardiopulmonary bypass (CPB) is a well-known cause of morbidity and

mortality The pathogenesis is not simply a consequence ofhypoperfusion but a complex interplay of CPB-related injury, oxidativestress, and activation of a systemic inflammatory reaction.46 Preexistingrenal insufficiency compounds this risk, necessitating precautions topreserve renal perfusion Associated risk factors include hypovolemiathat leads to vasoconstriction, the administration of nephrotoxic agentssuch as contrast media, embolic events in cases involving arterial vesselcross-clamping, renal ischemia, and inflammation.

Consideration of associated risks is important because perioperativerenal failure is associated with mortality rates of 60%–90% It is thereforevital to avoid factors that may augment preexisting renal dysfunction.47 , 48

In adult patients, 1% developed postoperative AKI after general surgicalprocedures 49; those at greatest risk were older men (≥56 years old).Although these data may not be directly applicable to children, childrenwith congestive heart failure, hypertension, preoperative renalinsufficiency, or ascites may also be at increased risk for AKI.Identification of those at risk is not a trivial exercise becausepostoperative AKI will increase postoperative morbidity and mortality

Preoperative Laboratory Evaluation

Routine preoperative blood testing in children has become unpopular inthe past few years.50 However, several preoperative laboratory testsshould be assessed in children with renal insufficiency This allows thepractitioner to determine the severity of the presenting disease andprovides a baseline that may be compared with intraoperative andpostoperative laboratory values to ensure proper protective renal care

As a broad standard, a complete blood cell count, BUN, electrolytes,creatinine, and coagulation panel should be performed preoperatively

An electrocardiogram should be obtained if there is a history ofhypertension and an echocardiogram if there is the suspicion of apericardial effusion and/or cardiomyopathy

Children with known renal failure, especially those with a significantreduction in renal function and those undergoing dialysis, requirepreoperative serum electrolyte analysis Abnormal serum potassiumconcentrations often occur in children with renal failure; acceptable limitsdepend on the local laboratory standards, the child's acid-base status,

and trends in the potassium concentration over time Chronichypokalemic or hyperkalemic states are less likely to cause cardiacmanifestations than acute changes Acute hypokalemia reduces thearrhythmia threshold and increases cardiac excitability; acutehyperkalemia may result in life-threatening arrhythmias A child withchronic renal failure whose serum potassium concentrations arechronically 5.5 to 6.0 mEq/L does not need correction of thehyperkalemia, whereas a child with an acute increase to a potassiumconcentration greater than 5.5 mEq/L often requires intervention beforethe surgical procedure and anesthesia Existing acidosis must be takeninto consideration in determining total body potassium concentrations,understanding that acute acidosis promotes extracellular hyperkalemia

at a rate of 0.5 mEq/L for every decrease in pH of 0.1 unit There areseveral approaches to treating hyperkalemia and were discussed earlier(see Table 28.6) Ideally, correction of hyperkalemia is accomplished byremoving potassium from the body using dialysis or sodium polystyrenesulfonate (Kayexalate) Urgent management in the operating room willinclude hyperventilation, nebulized albuterol and calcium, in addition to

a glucose and insulin infusion

Hypomagnesemia likewise predisposes a child to the risks ofsupraventricular and ventricular arrhythmias and should be correctedpreoperatively Hypermagnesemia or hypophosphatemia may causemuscle weakness and potentiate the action of neuromuscular blockingdrugs (NMBDs) Administration of calcium is helpful in treatinghyperkalemia or hypermagnesemia

Hemoglobin, hematocrit, and platelet counts should be part of thepreoperative evaluation Hemoglobin levels should be measured within

24 hours of the procedure and on the morning of the procedure if thehemoglobin is labile Morbidity and mortality in adult patients with renalfailure are increased at hemoglobin concentrations less than 11 g/dL.43,51These were likely the effect of anemia on the incidence of left ventricularhypertrophy; in children, this relationship may not hold true.Recombinant erythropoietin reduces the risks of cardiac compromisefrom left ventricular hypertrophy by increasing the hemoglobin tonormal values.52,53 Blood transfusion is generally not indicated if thehematocrit is more than 25%

The platelet count, although typically normal in children with renal

failure, does not portend platelet dysfunction The best metric to assessplatelet dysfunction in children with chronic renal failure is a prolongedbleeding time Signs of coagulopathy such as petechiae should alert thepractitioner of platelet dysfunction Platelet dysfunction does notnecessarily improve with platelet transfusion Dialysis, red blood celltransfusion, and erythropoietin improve platelet dysfunction.Desmopressin (0.3 µg/kg given by IV infusion over 15-20 minutes) canimprove the bleeding time in children with uremia and can minimizehypotension when given 1 hour before surgery It releases endothelialvon Willebrand factor/factor VIII complex and improves platelet functionfor 6 to 12 hours.

Depending on the degree of renal failure and suspected cardiacinvolvement, additional testing may include an electrocardiogram, achest radiograph, and an echocardiogram These tests can assist thepractitioner in determining evidence of left ventricular hypertrophy,arrhythmias, and the presence or absence of pericardial effusions

Measures of renal function essentially indicate the GFR and tubularfunction (diluting capacity) of the kidneys Urea and creatinine aretraditional indicators of renal function, with plasma urea being a verysimplistic marker of global renal function Creatinine, being relativelyconstantly produced by the muscles, can be used as a guide to GFR, butlacks sensitivity and specificity Recently, other endogenous [cystatin C,β-trace protein (BTP)] and exogenous (inulin, iohexol) biomarkers havebeen used to diagnose AKI after an intraoperative insult New molecules,such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injurymolecule-1 (KIM-1), and netrin-1, are a few of the many new promisingbiomarkers that await validation in the clinical setting.54–57

Increasingly in the adult literature, there is evidence that specificbiomarkers (such as endogenous ouabain, an adrenal stress hormone)can predict AKI in cardiac surgical patients, although to date, similardata in children have not been forthcoming.58

Perioperative Dialysis

In the child with renal failure, dialysis prevents hyperkalemia andremoves excess water However, excessive or overly aggressive dialysismay lead to electrolyte abnormalities and hypovolemia Accordingly, the

timing of this therapy or need for the therapy should be discussed withthe child's nephrologist Ideally, children with renal failure who undergo

intermittent hemodialysis should have dialysis on the day before surgery

rather than on the day of surgery to optimize their fluid and electrolytestatus and minimize problems with acute fluid shifts with hypotension,hypokalemia, and anticoagulation To limit any effects of residualheparin, the interval between dialysis and surgery should be 4 to 6 hours.Hemodialysis can be performed without heparin if is required urgently.Children who require peritoneal dialysis can undergo dialysis up untilthe day of surgery Peritoneal dialysis should be resumed with theconsideration that the child's pulmonary function must be able to toleratethe increased abdominal distention Consultation with the child'snephrologist is recommended to optimize the child's clinical status beforethe procedure and to arrange the appropriate timing of the peritonealdialysis

Medications

Children with renal failure may require their medications to be adjusted

in the perioperative period These medications typically includeantihypertensives, and although proceeding with elective surgery withmoderate hypertension may be acceptable, severe or labile hypertensionshould ideally be controlled before surgery Induction of anesthesia maycause hypotension in children with chronic hypertension, althoughpreloading with balanced salt solution may attenuate this effect There is

a temporal relationship between adults who take ACE inhibitors forblood pressure control on the day of surgery and hypotension atinduction of anesthesia and cardiac arrest.59 Moderate hypotension wassignificantly more frequent in those who discontinued their ACEinhibitor within 10 hours of induction of anesthesia compared with thosewho had not taken their medication for more than 10 hours beforeinduction.59 Additional studies in adults and opinion leaders recommendthat ACE inhibitors should be stopped on the day before surgery toprevent hypotension after induction of anesthesia, although thehypotension can be easily managed, especially during total IVanesthesia.60–62 All other antihypertensives, immunosuppressives, andsteroids should be continued Most other medications can be safely helduntil they can be resumed postoperatively Antacid prophylaxis may be

indicated for those with gastroesophageal reflux Premedication with abenzodiazepine such as midazolam may be valuable.

Finally, a knowledge of the child's daily fluid status including outputand input is important to appreciate If and when dialysis was lastperformed—and therefore the child's dry weight and actual weight—should be recorded on the day of surgery Tubular disorders, obstructiveuropathy, or hypoplastic/dysplastic kidneys may have fixed polyuria andare at risk for dehydration if oral intake is restricted (NPO) for longperiods Standard fasting intervals may be followed, including clearfluids until 2 hours before the procedure, to help prevent dehydrationand alleviate anxiety Alternatively, for the inpatient, maintenance IVfluids should be continued while the child is NPO

Intraoperative Management

Strategies for Renal Protection

Children with chronic renal failure frequently present with seriousmedical problems that complicate anesthesia.63 , 64 These problems stemmainly from fluid and electrolyte abnormalities, complications of chronicrenal failure such as anemia and hypertension, and differences in thepharmacokinetics of anesthetic agents in children with renal failure Themost important strategies for preserving renal function are optimization

of hemodynamics and intravascular volume and the avoidance orcautious use of drugs that are nephrotoxic (such as certain antibiotics,contrast agents, and nonsteroidal antiinflammatory drugs) Both theadministration of isotonic saline (as compared with hypotonic saline)and, more recently, IV sodium bicarbonate before the injection of contrastagents are protective against contrast induced nephropathy.65,66

Strict glycemic control by titrating insulin during cardiac and vascularsurgery has been associated in adults with a reduction in the incidence ofAKI requiring renal replacement therapy.65 This may not be true inchildren, in whom hyperinsulinemic hypoglycemia is more concerning inthe critically ill child and hyperglycemia is actually better tolerated.67Dopamine has long been considered renally protective, butconventional wisdom now would suggest that its actual effect is variable

and difficult to predict Fenoldopam, a selective dopamine 1–receptoragonist, increases GFR without the hypertension associated with the use

of dopamine It produces a more significant reduction in creatinine thandopamine and may therefore have a role in renoprotection Althoughseveral empirical measures have been recommended for renal protection

in the perioperative period, a Cochrane review concluded that nointerventions, whether pharmacologic or otherwise, protected the kidney

in the perioperative period.68

In a child with AKI and low urine output, it is tempting to administerdiuretics to increase RBF and flush the renal tubules However, the use ofdiuretics in a child with renal disease may worsen the renal failure bycausing hypovolemia and decreasing renal perfusion.69

Vascular Access

In addition to routine monitoring, the absolute need for arterial accessshould be cautiously considered because it may affect future shunt sites.Arterial access is useful to monitor blood pressure that may be labileduring the perioperative period and to measure blood gases andelectrolytes However, central venous access may achieve these samegoals as well as monitor volume status (as urine output is a poor metricfor renal perfusion in these children), secure IV access, and ensure thesafe and reliable delivery of vasoactive medications including calcium,and avoid compromising future arterial access Serum potassiumconcentrations must be monitored and corrected to avoid arrhythmias orconduction problems

Fluids and Blood Products

In the child with renal insufficiency, fluid management requires abalanced approach The child must receive adequate hydration toprevent further renal deterioration in an otherwise injured kidney.Children with renal failure and a history of hypertension are at risk forboth hypotension and hypertension and require some degree of fluidresuscitation for stability However, they also may havehypoalbuminemia with low oncotic pressure that puts them at risk forpulmonary edema Ideally, if the child is euvolemic, standard fluidtherapy based on typical surgical fluid management is preferred Fluidoverload must be avoided in all anuric children and in outpatients.Although common sense and years of practice suggest that normal salinesolution is preferable to lactated Ringer's solution because of thepotassium load in the latter, a series of adults who underwent kidneytransplantation showed that 19% of those who received IV saline hadpotassium concentrations of 6 mEq/L, and 31% had a metabolic acidosisthat required treatment compared with none for both the potassiumconcentration and metabolic acidosis in those who received lactatedRinger's solution.70 Lactated Ringer's solution or similar balanced saltsolutions should be considered for children with renal failure.

The debate over colloids versus crystalloids continues with renalfunction being an important endpoint While albumin can be used inchildren with renal disease, it confers little advantage over saline.Hexaethyl starch, on the other hand, may cause a coagulopathy as well asrenal dysfunction In a 2013 Cochrane review, researchers found noevidence that colloids conferred any advantage over clear fluids.71

Children with significant renal failure are at a greater risk for bleeding

in the perioperative period As a consequence, the hemoglobinconcentration should be monitored closely This is a classic and lethalcomplication in children with terminal uremia that results from plateletdysfunction in the presence of a normal coagulation profile and normalplatelet counts Blood and component therapy may be used inaccordance with surgical losses and to maintain the hemoglobinconcentration greater than 11 g/dL Other components that may beeffective to alleviate surgical oozing or occult bleeding should be givenbased on the clinical need because coagulation studies may not be trueindexes of the coagulation status in children with platelet dysfunction

Anesthetic Agents

The pharmacokinetics and pharmacodynamics of anesthetic agents andperioperative medications may be altered in children with renal failure.The medications most likely to be affected are those that depend on renalexcretion, such as the hydrophilic, highly ionized agents Repeated doses

of medications that depend primarily on renal excretion for eliminationshould be administered at greater intervals or in smaller doses than theyare given otherwise Examples of commonly used perioperativemedications that primarily depend on renal elimination are penicillins,cephalosporins, aminoglycosides, vancomycin, and digoxin

Anesthetic agents should be tailored according to the circumstancesand child For example, the duration of action of medications delivered

as a single bolus depends more on redistribution than on elimination Ifthe volume of distribution of the medication is unchanged, the singlebolus dose should be unchanged Medications that depend only in part

on renal elimination (e.g., rocuronium or vecuronium) have a normalduration of action when delivered as a bolus or short-term infusion.Many anesthetics depend in part on renal elimination, includingpancuronium, vecuronium, rocuronium, atropine, glycopyrrolate, andneostigmine

Induction of anesthesia may be carried out safely as long as the child iseuvolemic and the pharmacokinetics and pharmacodynamics of theinduction agent are understood and accounted for Anesthetic agentsmay be affected by the presence of anemia, acidosis, and altered drugbinding owing to hypoproteinemia in children with renal disease.Antihypertensives such as ACE inhibitors, particularly in combinationwith diuretics, may lead to profound hypotension at induction ofanesthesia.72

The dose of propofol to induce anesthesia using the bispectral indexand clinical signs to indicate the state of hypnosis in adult patients withrenal failure were significantly greater than in those without renaldisease.73 This has been attributed to a larger volume of distribution inpatients with renal failure, consistent with previous studies ofthiopental.74 Anemia is another contributing factor It may indirectlycause a greater plasma volume and greater cardiac output Whenpropofol is delivered as an infusion, no significant differences in

pharmacokinetic (principally clearance) or pharmacodynamic parametershave been observed.75 There is also some evidence to suggest thatpropofol, when compared with sevoflurane, may be renoprotective as aresult of its ability to attenuate the perioperative increase inproinflammatory mediators.46

There are insufficient data regarding the use of inhalational anestheticsfor induction in children with renal impairment For maintenance ofanesthesia in adults, desflurane and isoflurane do not further impairrenal function in those with preexisting renal disease.76 Sevoflurane atlow flows is associated with increased circuit concentrations ofcompound A, which is nephrotoxic in rats but not in humans.77–79 Inadults with normal renal function, low-flow sevoflurane anesthesia hasbeen associated with mild, transient proteinuria but no changes in BUN,creatinine level, or creatinine clearance.79 In adults with renalinsufficiency, low-flow sevoflurane is as safe as low-flow isoflurane interms of kidney function.78 Overall, sevoflurane is considered safe inpatients with renal disease, but low flows are best avoided Becausedesflurane is minimally metabolized (rate of 0.2%) in vivo, it may bepreferred even at very low flows (1 L/minute)

NMBDs have evolved over the years to provide a choice of relaxantsfor use in children with renal disease Children with chronic renal failuremay have existing autonomic neuropathy and associated delayed gastricemptying that puts them at risk for aspiration Along with renalimplications, aspiration should be anticipated when choosing an NMBDfor airway management Succinylcholine is often avoided in childrenwith renal failure because of its well-known propensity for increasingserum potassium However, succinylcholine does not increase theplasma potassium concentration in patients with renal failure any morethan in patients with normal renal function (0.5–0.8 mEq/L of potassium)unless a peripheral neuropathy is present.80,81 The plasma concentration

of potassium is chronically increased in renal failure, which implies thatthe intracellular and extracellular potassium concentrations are inequilibrium As a result, the usual 0.5- to 1-mEq/L increase in serumpotassium after succinylcholine causes no clinical manifestations, despitethe large absolute concentration of potassium This contrasts withpatients with acute hyperkalemia in whom the intracellular andextracellular potassium concentrations are in disequilibrium, which

predisposes these children to ventricular arrhythmias aftersuccinylcholine In the latter case, succinylcholine is relativelycontraindicated, whereas in the former case, it is not contraindicated.The pharmacodynamics of NMBDs in children with renal insufficiencymerit consideration The onset time of rocuronium in children with renalfailure (>2 minutes) was significantly greater than in the control children(1.5 minutes) This difference was attributed to a greater volume ofdistribution, decreased serum albumin concentrations, and possibly to areduced cardiac output in children with renal failure who were takingantihypertensives The slower onset time of rocuronium in children withrenal failure must be considered when a rapid-sequence intubation isrequired and succinylcholine is contraindicated On the other hand, theduration of action of rocuronium in children with normal renal functionand end-stage renal disease is similar82; the time to recover a train-of-fourratio of 70% was 29 minutes in both groups with a 0.3-mg/kg dose This

is not surprising because elimination of rocuronium is predominantlybiliary and not via the kidneys

NMBDs such as atracurium and cisatracurium are ideal choices forchildren with renal insufficiency because their elimination is completelyindependent of the kidney Despite the fact that both agents undergospontaneous degradation by plasma esterase and Hofmann elimination,neuromuscular blockade should still be monitored.83 Therefore withappropriate monitoring and dosing, atracurium, cisatracurium,vecuronium, and rocuronium are all acceptable NMBDs in children withrenal disease and provide reliable durations of action after a single bolusdose

If a prolonged neuromuscular blockade occurs, hypermagnesemiashould be ruled out In this case, calcium may be administered to helpantagonize the blockade The elimination of neostigmine may be delayedbeyond elimination of atropine or glycopyrrolate, and muscarinic effectssuch as bradycardia, increased secretions, or bronchospasm maytheoretically occur postoperatively after antagonism

Sugammadex is a binding agent selective for aminosteroidal NMBDssuch as rocuronium and vecuronium It is entirely renally excreted with

an elimination half-life of approximately 100 minutes As discussedelsewhere, rocuronium is metabolized almost entirely in the liver butwhen it is bound to sugammadex, it is both inactivated and effectively

removed from the circulation; the rocuronium-sugammadex complex iseliminated by the kidney Special consideration should therefore be given

to patients with renal failure.84 Suggamadex dosing in mild to moderaterenal dysfunction is the same as in patients with normal renal function; it

is not recommended for those with severe renal failure.85 In a patientwith normal renal function, rocuronium can be redosed in about 25minutes after sugammadex administration Because there is currently noredosing data for patients with renal failure, the use of sugammadexshould be carefully considered

Remifentanil may be a preferred choice for a maintenance opioid in theintraoperative period in children with renal insufficiency because of itsrapid metabolism by nonspecific blood and tissue esterases Thepharmacokinetics and pharmacodynamics of remifentanil are not altered

in patients with renal disease, but the principal metabolite of remifentanilhas reduced elimination,86 , 87 which is not clinically relevant Doses ofother opioids should be reduced by 30% to 50% to avoid respiratorydepression in children with chronic renal failure Active metabolites ofmorphine and meperidine (no longer recommended for children otherthan to treat shivering) can likewise accumulate in patients with renalfailure, whereas those of fentanyl and sufentanil do not Dialysis may berequired to eliminate these active metabolites.88 Hence, the latter opioidsare preferred when remifentanil is not indicated.89–93 Prolongedantagonism of opioid effects with naloxone can be expected in renalfailure patients

Dexmedetomidine, an α2-adrenoceptor agonist, has diuretic propertiesvia its suppression of vasopressin secretion GFR and renal blood floware enhanced, thereby increasing urine output Some advocate its use inprotecting against contrast-induced nephropathy, but it has also beenshown to have an antiinflammatory effect It has been shown to reducelevels of harmful inflammatory molecules such as tumor necrosis factor-

α (TNF-α) and increase proteins such as bone morphogenetic protein-7(BMP-7), thought to be protective against sepsis-induced AKI.94 Theclinical efficacy of this has yet to be established, but dexmedetomidinehas been associated with improved short-term mortality in adult patientswith sepsis and children after surgery for congenital heart disease While

it is metabolized in the liver, none of the renally excreted metabolites arethought to be active The renoprotective effect of dexmedetomidine