PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

Perioperative management ofthe patient with chronickidney diseaseMark Dougherty

Stephen T Webb

AbstractThe prevalence of chronic kidney disease (CKD) is increasing. Periopera-

tive management of patients with CKD aims to control modifiable risk

factors associated with acute kidney injury (AKI). AKI on the background

of CKD may lead to dialysis dependency. CKD has widespread cardiovas-

cular, endocrine, metabolic and haematological effects. Preoperative

assessment and preparation require multidisciplinary input from the

surgical, anaesthetic and nephrology teams. Perioperative care should

ensure the correction of hypovolaemia, maintenance of renal blood

flow and perfusion pressure, prevention of radiocontrast-induced nephro-

toxicity, avoidance of nephrotoxic drugs and treatment of urinary tract

obstruction.

Keywords Acute kidney injury; chronic kidney disease; nephrotoxicity;

renal blood flow

Stages of chronic kidney disease

Stage Degree of impairment GFR (ml/min/1.73 m2)

1 Normal function, but structural

or genetic disposition

to kidney disease

>90

Introduction

Chronic kidney disease (CKD) is a progressive, multi-system

condition that encompasses a wide clinical spectrum (Table 1)

ranging from entirely normal renal function to end-stage renal

failure (ESRF). It is postulated that renal function gradually

deteriorates as a result of an underlying predisposition or some

other renal ‘insult’. The rate and extent of deterioration varies

between individuals and depends on the aetiology of the renal

impairment.

The most recent UK Renal Registry report suggests that the

incidence of CKD requiring renal replacement therapy (RRT) is

w100 per million of population, and that the prevalence of stage

5 CKD is increasing by >4% per year. The prevalence of CKD

stages 3e5 is around 5%. Because the majority of individuals are

asymptomatic, the prevalence of CKD stages 1e2 is unknown,

but likely to be significant.

The aim of perioperative management is to control factors that

may result in acute kidney injury (AKI) and a further decline in

renal function (Table 2). The onset of perioperative AKI in the

Mark Dougherty MB BCh BAO MRCP FCARCSI is a Specialist Registrar in

Anaesthesia at The Royal Hospitals, Belfast, UK. Conflicts of interest:

none declared.

Stephen T Webb MB BCh BAO FRCA EDIC is a Consultant in Anaesthesia &

Intensive Care Medicine at Papworth Hospital, Cambridge, UK. Conflicts

of interest: none declared.

SURGERY 28:9 433

setting of CKD is a serious complication that is associated with

considerable morbidity and mortality.

Aetiology

A gradual fall in renal function is a normal consequence of

ageing, but rarely results in ESRF. The two most common

medical conditions associated with CKD are diabetes mellitus

and arterial hypertension. Control of the underlying condition

(Box 1) is crucial in preventing further deterioration of renal

function.

Multi-system effects

The widespread multi-system effects of CKD reflect the functions

of the kidney (Box 2).

Fluid overload

Sodium and water retention occurs as functional nephrons are

lost. Perioperative fluid restriction may be necessary for fluid

overloaded patients.

Electrolyte derangement

Hyponatraemia or hypernatraemia reflects the combination of

impaired renal handling of sodium and water. Hyperkalaemia

results from reduced renal secretion, metabolic acidosis and co-

existing use of angiotensin-converting enzyme (ACE) inhibitors

and angiotensin receptor blockers (ARBs).

Anaemia

The anaemia associated with CKD is multifactorial in origin.

Dietary haematinic deficiency (e.g. iron, folate and vitamin B12),

occult gastrointestinal blood loss and impaired renal erythro-

poietin production all contribute to the development of anaemia.

Patients with CKD are often treated with erythropoietin. Blood

product transfusion is avoided if possible, to prevent red cell

allosensitization reducing the success of renal transplantation.

Coagulopathy

Although routine laboratory coagulation test results may be

normal, platelet dysfunction is often present and the bleeding

time may be prolonged. Platelet dysfunction may be treated by

2 Mildly reduced function with

findings of stage 1

60e89

3 Moderately reduced function 30e59

4 Severely reduced function 15e29

5 End-stage renal disease or

dialysis dependant

<15

GFR, glomerular filtration rate

Table 1

� 2010 Elsevier Ltd. All rights reserved.

Classification and staging system for acute kidneyinjury

Stage Serum creatinine criteria Urine output criteria

1 Increase in serum

creatinine �0.3 mg/dl

(�26.4 mmol/litre) OR

Increase to more than

or equal to 150%e200%

(1.5e2-fold) from baseline

<0.5 ml/kg/hour for

6 hours

2 Increase in serum creatinine

to more than 200%e300%

(>2e3-fold) from baseline

<0.5 ml/kg/hour for

12 hours

3 Increase in serum creatinine

to more than 300% (>3-fold)

from baseline OR

Serum creatinine �4.0 mg/dl

(�354 mmol/litre) with an

acute increase >0.5 mg/dl

(>44 mmol/litre)

<0.3 ml/kg/hour for

24 hours

OR Anuria for

12 hours

Note: given wide variation in indications and timing of initiation of renal

replacement therapy (RRT), individuals who receive RRT are considered to

have met the criteria for stage 3 irrespective of the stage they are in at the

time of RRT

Table 2

Functions of the kidney

Regulation of water and electrolytes

Maintenance of acidebase balance

Excretion of metabolic waste products and water-soluble drugs

Endocrine functions e erythropoietin, renin, vitamin D

Box 2

PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

the use of erythropoietin or efficient dialysis. Desmopressin

(1-deamino-8-D-arginine vasopressin; DDAVP) may be used in

the perioperative period to temporarily reduce the bleeding time

by mobilizing von Willebrand factor.

Renal osteodystrophy

Phosphate retention and impaired vitamin D production results

in reduced calcium absorption from the gastrointestinal tract and

subsequent hypocalcaemia. Hypocalcaemia increases parathor-

mone production (secondary hyperparathyroidism), which

increases bone resorption. Renal osteodystrophy causes bone

pain and proximal myopathy, and predisposes to pathological

fractures. Special care must be taken during patient positioning

in order to avoid injury.

Cardiovascular dysfunction

Hypertension may be both the cause and consequence of CKD.

Hypertension may be idiopathic, related to sodium and water

Causes of chronic kidney disease

Diabetes mellitus

Hypertension

Renal vascular disease

Glomerulonephropathy

Tubulointerstitial disease

Hereditary conditions

Obstructive uropathy

Box 1

SURGERY 28:9 434

retention, or secondary to excessive renin production or renal

artery stenosis. The autoregulation plateau, within which renal

blood flow is largely independent of perfusion pressure, is shifted

to the right, making the kidneys more susceptible to renal

hypoperfusion at comparatively normal blood pressures.

Hypertension and impaired calcium handling leads to accelerated

occlusive arterial disease. Co-existing coronary, cerebral and

peripheral arterial disease is common.

Immunosuppression

Immune function, particularly phagocytosis and chemotaxis, is

impaired in CKD. Protein-losing nephropathy may result in

increased excretion of immunoglobulins. Patients with CKD are

therefore prone to infection and impaired wound healing.

Malnutrition

Malnutrition in CKD is complex. Uraemic malnutrition may be

secondary to a decrease in the renal excretion of the so-called

satiety protein leptin. Increased leptin levels suppress insulin

release and favour protein catabolism. Increased oxidative stress,

and impaired gluconeogenesis and protein metabolism all

contribute to malnutrition. Malnutrition further increases the

risks of infection and impaired wound healing.

Peripheral neuropathy

Uraemic neuropathy is predominantly a peripheral sensorimotor

polyneuropathy. There is a risk of pressure-induced peripheral

neuropathy during anaesthesia.

Disordered drug excretion

Inappropriate drug dosing in CKD is an important cause of

inadvertent adverse effects. Impaired renal function results in

reduced glomerular filtration and reduced tubular excretion. The

accumulation of uraemic toxins alters the degree of plasma

protein binding and therefore affects the plasma levels of acidic

drugs. The level of a1 acid-glycoprotein is increased in CKD

leading to increased binding of basic drugs and reduced plasma

levels. Alteration in drug doses or intervals will often be required

in patients with CKD.

Preoperative assessment

Clinical assessment

The management of patients with renal dysfunction requires the

collaboration of the surgical, anaesthetic and nephrology teams.

As well as establishing the aetiology and severity of CKD, it is

important to identify the presence of co-existing conditions. The

volume of daily urine output, usual body weight and requirement

� 2010 Elsevier Ltd. All rights reserved.

PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

for daily fluid restriction should be evaluated. An assessment

should be made of renal replacement therapy (RRT) access, type

and schedule. Ideally, surgery should be scheduled to minimize

interruption to RRT. Vascular access and non-invasive blood

pressure measurement should be avoided in limbs where an

arteriovenous fistula has been created for dialysis. Determining

drug regimens, and ensuring the continuation of essential

medication with minimal adverse effect to the fluid, electrolyte

and haemodynamic status of the patient.

Laboratory tests

A full blood count will determine the presence and severity of

anaemia or thrombocytopaenia. The bleeding time should be

measured as coagulation studies are likely to be within normal

limits. Baseline serum electrolyte (Naþ, Kþ, Ca2þ, Mg2þ, Cl�),urea and creatinine levels should be recorded.

Electrocardiogram

The resting 12-lead electrocardiograph (ECG) may demonstrate

the presence of established myocardial infarction, uraemic peri-

carditis or cardiac chamber hypertrophy. Exercise ECG testing or

cardiopulmonary exercise testing may be required.

Chest radiography

Chest radiography may demonstrate cardiomegaly, pulmonary

venous congestion or metastatic calcification.

Perioperative management

Modifiable factors should be controlled to prevent AKI in patients

with CKD (Table 3):

� correction of hypovolaemia

� maintenance of renal perfusion pressure and blood flow

� prevention of radiocontrast-induced nephrotoxicity

� avoidance of nephrotoxic drugs

� treatment of urinary tract obstruction.

Risk factors for acute kidney injury

Preoperative factors Intraoperative factors

Chronic disease

- Advanced age

- Female sex

- Chronic renal disease

- Diabetes mellitus

- Chronic cardiac failure

- Aortic and peripheral vascular disease

- Chronic liver disease

- Genetic predisposition

Acute conditions

- Hypovolaemia

- Sepsis

- Multiple organ dysfunction syndrome

- Drug nephrotoxicity

Type of surgery

- Cardiac

- Aortic

- Peripheral vascu

- Non-renal solid o

Other factors

- Emergency surge

- Aortic clamp pla

- Intra-operative ra

Table 3

SURGERY 28:9 435

Correction of hypovolaemia

Intravascular volume depletion may be avoided by monitoring

fluid intake and output, repeated observation of clinical signs and

the appropriate use of invasive haemodynamic monitoring. Peri-

operative hypovolaemia should be rapidly but judiciously cor-

rected by volume expansionwith intravenous fluids. The choice of

fluid is a matter for personal preference and remains the subject of

debate.With the exceptionofHartmann’s solution,which contains

lactate, all isotonic crystalloids can be used safely in CKD. The

safety and long-term consequences of the use of synthetic colloids

(e.g. gelatinins and hydroxyethyl starch) in CKD have not yet been

fully elucidated. A balanced approach, using a combination of

crystalloid maintenance and colloid is recommended.

Maintenance of renal perfusion

The maintenance of adequate renal perfusion requires the

‘defence’ of both cardiac output and systemic arterial pressure. The

initial approach should be intravascular volume expansion to

correct hypovolaemia. Inotropic and vasopressor therapy may

then be initiated for the management of low cardiac output and

systemic arterial hypotension respectively. Dopamine or dobut-

amine may be used to improve cardiac output and mean arterial

pressurebut haveno specific renal protective effect.Noradrenaline

is an effective first-line vasopressor agent. There is no firm

evidence to suggest that the drug compromises renal, hepatic or

gastrointestinal blood flow when used to treat arterial hypoten-

sion. The optimal therapeutic target for systemic arterial pressure

for renal protection has not been established. A minimum mean

arterial pressure of 65e75mmHg is often quoted, however a higher

targetmaybenecessary in patientswith pre-existing hypertension.

Prevention of radiocontrast-induced nephropathy

The benefit of isotonic intravascular volume expansion for the

prevention of radiocontrast-induced nephropathy has been

clearly demonstrated. However, the ideal composition of such

fluid and the optimal rate of infusion have not been determined

and should be individualized. Both sodium chloride 0.9% and

Postoperative factors

lar

rgan transplantation

ry

cement

diocontrast

Acute conditions

- Acute cardiac dysfunction

- Haemorrhage

- Hypovolaemia

- Sepsis

- Rhabdomyolysis

- Intra-abdominal hypertension

- Multiple organ dysfunction syndrome

- Drug nephrotoxicity

� 2010 Elsevier Ltd. All rights reserved.

Perioperative renal protection in chronic kidneydisease

Preoperative

- Optimize volume status, cardiac output and systemic arterial

pressure

- Withhold nephrotoxic drugs

- Maintain glycaemic control in diabetic patients

- Correct metabolic and electrolyte disturbances

- Arrange preoperative dialysis for dialysis-dependent patients

- Administer isotonic intravenous fluids for prevention of

radiocontrast-induced nephropathy

Intraoperative

- Optimize volume status, cardiac output and systemic arterial

pressure

- Avoid nephrotoxic drugs

- Maintain glycaemic control in diabetic patients

Postoperative

- Avoid nephrotoxic drugs

- Maintain glycaemic control in diabetic patients

- Promptly treat acute cardiac dysfunction

- Control haemorrhage

- Manage sepsis aggressively

- Recognize and treat rhabdomyolysis

- Recognize and treat intra-abdominal hypertension

- Provide appropriate organ support for multiple organ

dysfunction syndrome

- Institute renal replacement therapy if required for acute

kidney injury

- Recommence dialysis for dialysis-dependent patients

Box 3

PERIOPERATIVE MANAGEMENT OF CO-MORBID CONDITIONS

sodium bicarbonate 4.2% appear to be effective. The use of

N-acetylcysteine to prevent radiocontrast-induced nephropathy

remains the subject of ongoing investigation. Patients with CKD

who require radiocontrast will benefit from the use of the lowest

possible volume of non-ionic, iso-osmolar contrast in conjunc-

tion with isotonic intravenous fluids.

Avoidance of nephrotoxic drugs

Minimizing exposure to nephrotoxic drugs is crucial in patients

with CKD. The use of once-daily aminoglycoside dosing (e.g.

SURGERY 28:9 436

gentamicin, vancomycin) and the use of lipid formulations of

amphotericin B have been demonstrated to reduce the risk of

nephrotoxicity associated with these drugs. Recently, concerns

were raised about the risk of AKI associated with the use of the

antifibrinolytic agent aprotinin in cardiac surgery. Evidence

suggests that the use of aprotinin during coronary artery bypass

graft surgery may be associated with an increased risk of AKI

requiring RRT. The potential for drug-induced nephrotoxicity

must be balanced against the therapeutic benefits and the clinical

context.

Urinary tract obstruction

The early diagnosis and institution of therapeutic measures to

overcome urinary tract obstruction are important. Urinary cath-

eterization is required to accurately assess urine output and

ultrasound imaging is necessary to identify the presence and site

of obstruction. Early urology consultation is recommended.

Renal replacement therapy

The optimal type and timing of RRT in AKI superimposed on

CKD is unclear. The presence of pulmonary oedema, refractory

hyperkalaemia, metabolic acidosis or clinical features of uraemia

should be taken as absolute indications for RRT. Clinical

outcomes may be improved if RRT is commenced early. A

summary of perioperative renal protection measures in CKD is

given in Box 3. A

FURTHER READING

Acute Kidney Injury Network (AKIN), http://www.akinet.org/.

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines,

http://www.kdigo.org/clinical_practice_guidelines/index.php.

National Kidney Foundation Kidney Disease Outcome Quality Initiative

(NKF KDOQI) guidelines, http://www.kidney.org/professionals/kdoqi/

guidelines_commentaries.cfm.

NICE guidance: chronic kidney disease, http://guidance.nice.org.uk/CG73.

UK Renal Association (UKRA) guidelines, http://www.renal.org/Clinical/

GuidelinesSection/Guidelines.aspx.

UK Renal Registry, http://www.renalreg.com.

Webb ST, Allen JSD. Perioperative renal protection. Cont Educ Anaesth Crit

Care Pain 2008; 8: 176e80.

Zacharias M, Conlon NP, Herbison GP, Sivalingam P, Walker RJ,

Hovhannisyan K. Interventions for protecting renal function in the

perioperative period. Cochrane Database Syst Rev 2008 Oct 8; (4):

CD003590.

� 2010 Elsevier Ltd. All rights reserved.