Chronic kidney disease and anaesthesia

Learning objectives.

By reading this article, you should be able to:

• •Describe the aetiology of chronic kidney disease (CKD).
• •Explain the pathophysiology of complications relevant to anaesthesia for patients with CKD.
• •Detail the changes in drug handling in CKD.
• •Discuss the issues surrounding the perioperative management of patients with CKD.

Key points.

• •Chronic kidney disease has complications in multiple systems.
• •Coexistent cardiovascular disease is common.
• •Management of CKD is centred around treating reversible causes, slowing the rate of disease progression and treating complications.
• •Altered pharmacokinetics may result in drug accumulation and toxicity.
• •Fluid balance can be difficult to achieve and should be monitored carefully.

The importance of kidney function is reflected in the layers of protection the body affords them. They have a vast reserve of function, perfusion is maintained at the expense of other organs and vulnerability to physical insult is reduced by embedding the kidneys in a cushioning fat pad, high at the back of the abdominal cavity within a protective bony cage. With these defences, kidney failure represents overwhelming damage that frequently includes other organs. The multisystem pathology associated with kidney failure can have profound effects on anaesthesia, so anaesthetists must know how to assess these patients, when to investigate further and how to treat the common complications.

Epidemiology

Chronic kidney disease (CKD) is common. More than 1.8 million people in the UK have a diagnosis of CKD with around a further million thought to be undiagnosed. The estimated disease prevalence in the UK of CKD stages 3–5 is thought to be between 4.3% and 8.5% and this appears to be increasing.¹

The global prevalence of CKD is 9.1%. In 2017, CKD was recognised as the 12th leading cause of death, responsible for 1.2 million deaths each year worldwide. Deaths attributable to CKD are set to increase further, with predictive modelling suggesting that by 2040 2.2 million people will die annually because of CKD. This is a best-case scenario. A worst-case scenario would see a projection of up to 4 million people dying. Such increases can in part be attributable to the increases in the prevalence of risk factors such as diabetes and hypertension.²

This disease is more common in smokers and certain ethnic groups (Asian, African, Afro-Caribbean). The causes of CKD are legion (Table 1).³ The most common causes are diabetes and hypertension. Hypertension is both a cause and consequence of CKD.

Table 1.

Aetiology and risk factors for chronic kidney disease.

Relating to comorbidities	Vascular disease including renal vascular stenosis
	Hypertension
	Type 2 diabetes mellitus
Intrinsic renal disease	Glomerulonephritis
	Acute kidney injury
	Interstitial nephritis
	Nephropathies	Infective (e.g. pyelonephritis)
		Obstructive (e.g. prostatic hypertrophy, nephrolithiasis)
		Reflux
Genetic	Polycystic kidney disease
	Alport syndrome
	Fabry disease
	Cystinosis
Metabolic	Hypercalcaemia
	Hyperparathyroidism causing nephrocalcinosis
	Oxalosis
Systemic disease	Amyloidosis
Autoimmune disease	Goodpasture syndrome
	Scleroderma
	IgA vasculitis
	Systemic lupus erythematosus
Neoplasm	Myeloma
	Renal tumour
Toxins	Lead poisoning
Drug-related	NSAID use nephropathy
	Calcineurin inhibitors
	Chemotherapeutic agents
Other	Haemolytic uraemic syndrome
	Gout
	Obstructive uropathy

Definition and classification

Chronic kidney disease is defined by the Renal Association as an abnormality of kidney structure or function that lasts more than 3 months. It only becomes evident when fewer than 40% of nephrons are functioning. Tests which enable diagnosis include electrolyte abnormalities due to tubular disorders, proteinuria (albumin to creatinine ratio (ACR) > 3 mg/mmol), haematuria of renal origin, histological or radiological abnormalities in structure and abnormal function with resultant raised creatinine and/or cystatin C (eGFR <60 ml/min/1.73 m²) on more than two occasions 90 days apart.⁴ Additional abnormalities that may point to a diagnosis of CKD include uraemia and anaemia. Classification aids risk stratification and is based on eGFR and the presence of proteinuria (Fig 1).

Figure 1.

Classification of chronic kidney disease. GFR, glomerular filtration rate; CKD, chronic kidney disease; KDIGO, Kidney Disease: Improving Global Outcomes.

Glomerular filtration rate (GFR) is the internationally accepted measure to express renal function. However, GFR is not routinely measured because it is a complex procedure that involves measurement of plasma or urinary clearance of an exogenous marker such as inulin. More commonly, eGFR is used: this uses serum creatinine, cystatin, or both, age, and sex to mathematically derive the eGFR. To date, there has been a correction factor used for people of African-Caribbean or African family origin. However, the most recent guidance from the National Institute of Health and Care Excellence (NICE) no longer recommends a correction factor for ethnicity.⁵ Adjusting for ethnicity may overestimate actual GFR and consequently result in an underdiagnosis of CKD in black people.⁶

The 2021 CKD-EPI equation is recommended for calculation of eGFR. This is more accurate than other equations such as the Modification of Diet in Renal Disease (MDRD) study equation and the Cockroft–Gault equation for creatinine clearance. The CKD-EPI equation can be used with or without cystatin C. Cystatin C is a protein that is freely filtered at the glomerulus, reabsorbed and metabolised by tubular cells. Unlike creatinine, its metabolism is independent of muscle mass. The inclusion of cystatin C in the CKD-EPI formula may provide a more accurate estimate of GFR.⁷

Manifestations of renal impairment

Metabolic changes

The ability of the kidneys to excrete water and sodium is impaired, causing difficulty in handling large fluid loads. As glomerular filtration decreases, sodium and water are retained and because of the increased hydrostatic pressure, fluid moves into the extravascular space leading to the clinical manifestations of fluid overload such as generalised and pulmonary oedema. Paradoxically, the kidneys do not fare well in the face of dehydration as renal hypoperfusion is a common prerenal cause of acute kidney injury (AKI) and can compound any pre-existing disease. The ability of the kidneys to dilute or concentrate urine becomes progressively impaired as CKD develops. Fluid balance is fragile and must be managed carefully.⁸

Renal function is essential in electrolyte homeostasis, and consequently CKD can cause metabolic disturbances including hyperkalaemia, metabolic acidosis, hyperphosphataemia, hypocalcaemia, hypermagnesaemia, hyperuricaemia and hypoalbuminaemia. The most encountered and clinically concerning metabolic disturbances in patients with severe uncorrected renal disease are metabolic acidosis and hyperkalaemia. Metabolic acidosis results from a combination of increased production of non-volatile acids, increased bicarbonate loss (and therefore decreased buffering capacity) and decreased renal excretion of acid. Urinary bicarbonate loss is caused by reduced tubular bicarbonate reabsorption. Ammonium (and therefore acid) excretion is decreased because of the reduction in GFR, which reflects a decline in the number of functioning nephrons.⁹ Bicarbonate supplements are prescribed to treat metabolic acidosis.

Loss of nephron function results in renal retention of potassium. As GFR declines, the remaining nephrons adapt by increasing renal excretion and this works as a compensatory mechanism when the GFR is >15 ml min⁻¹. Thereafter, extrarenal mechanisms for handling potassium become vital: the colon increases its capacity to excrete potassium. Saturation of compensatory mechanisms leads to hyperkalaemia. The process described is compounded by metabolic acidosis, which causes potassium to move from the intracellular to the extracellular compartment. Patients with coexistent diabetes may be insulin deficient or insensitive, which limits the shift of potassium to the intracellular space. Drug-induced hyperkalaemia is common in patients with CKD.¹⁰ The tendency towards hyperkalaemia is ameliorated by instituting a low potassium diet and avoiding drugs known to cause hyperkalaemia.

Cardiovascular system

Hypertension is common in patients with CKD. This may be the primary cause of the CKD or because of chronic salt and water retention, excess renin production, or both.

Chronic kidney disease is associated with an increased risk of ischaemic heart disease. Most patients do not progress to end-stage renal failure but die as a result of fatal cardiovascular complications (myocardial infarction, heart failure or stroke).¹¹ The underlying pathophysiological changes are thought to be a combination of increased circulating inflammatory mediators, hypercoagulability, arterial calcification and endothelial dysfunction.

Left ventricular hypertrophy can occur because of chronic volume overload, pressure overload, or both. Volume overload is caused by water and sodium retention, the presence of an arteriovenous fistula or chronic anaemia leading to a hyperdynamic circulation with increased stroke volume and tachycardia as a compensatory response. Pressure overload is caused by hypertension and arteriosclerosis. The hypertrophy is associated with myocardial fibrosis and impaired myocardial relaxation, which can lead to diastolic dysfunction and arrythmias. Reduced left ventricular compliance results in increased sensitivity to changes in volume.

Atherosclerosis is accelerated in patients with CKD. The postulated mechanism involves impaired endothelial function, low-grade inflammation and dyslipidaemia. Changes in lipoprotein metabolism result in an accumulation of intermediate density lipoprotein. Activation of the renin–angiotensin system leads to production of reactive oxygen species which cause endothelial dysfunction and promote vascular remodelling. Dyslipidaemia is treated with statin therapy and this reduces cardiovascular risk.

Patients undergoing renal replacement therapy (RRT) may exhibit calciphylaxis, which describes accumulation of calcium in small blood vessels. This is positively correlated with vascular calcification and valvular heart disease.

Patients with CKD are predisposed to pulmonary oedema because of fluid overload, left ventricular failure, or both. Volume overload is treated with dietary sodium restriction and diuretic therapy.

Severe uraemia can cause pericarditis.¹²

Respiratory system

The tendency towards development of fluid overload can cause pulmonary oedema and pleural effusions, with a decrease in pulmonary compliance, reduction in functional residual capacity and an increase in ventilation–perfusion mismatch.

Restrictive pulmonary dysfunction is common in patients with CKD. This may be attributable to multisystem interactions between the heart, kidneys and lungs involving inflammation and protein-energy wasting (reduced capacity for protein and energy storage). However, the exact pathophysiology is yet to be elucidated.¹³

Haematological system

A reduction in the synthetic function of the kidney causes lower levels of erythropoietin leading to anaemia. Guidance on monitoring and treatment of anaemia in CKD varies between institutions. Treatment modalities include iron supplementation (oral or intravenous) and intravenous erythropoiesis-stimulating agents.¹⁴

Historically, patients with end-stage renal failure were considered hypocoagulable. Acquired uraemic platelet dysfunction and thromboasthenia decrease platelet adhesion and increase vessel wall fragility, which contribute to bleeding diatheses. Platelet function is abnormal because of decreased adenosine diphosphate (ADP) content, impaired aggregation to ADP, an increase in endogenous nitric oxide production, a reduction in thromboxane A₂ and defective interaction of von Willebrand factor with platelet glycoprotein IIb–IIIa receptors. Although skin bleeding time has been noted to be prolonged, this has not been reflected in laboratory tests of coagulation such as prothrombin time and activated thromboplastin time.¹⁵

Chronic kidney disease also represents a prothrombotic state caused by decreased fibrinolysis, increased initial fibrin formation, increased fibrin–platelet interaction and increased qualitative platelet function. It is considered an independent risk factor for venous thromboembolism (VTE). The risk of VTE increases with decreasing eGFR, increasing age and other more general risk factors such as immobilisation and surgery.¹⁶

Haemostasis can be further complicated by underlying disease, inherited coagulopathy and the use of drugs affecting blood clotting such as anticoagulants and antiplatelet drugs.

Anaemia is common in end-stage renal failure, and patients may take erythropoiesis-stimulating agents such as erythropoietin or darbepoetin alfa.

Gastrointestinal system

Symptoms of CKD such as anorexia, nausea, vomiting and diarrhoea can render patients dehydrated. Poor nutritional intake results in impaired wound healing in the postoperative period. This can also be attributable to vascular disease and underlying comorbidities such as diabetes and scleroderma. Delayed gastric emptying may be a consequence of autonomic neuropathy.

Central nervous system

Chronic kidney disease may result in a wide array of neurological manifestations including myoclonus, asterixis, chorea, uraemic encephalopathy and seizures.

The incidence of seizures in patients with CKD is approximately 10%.¹⁷ One third of patients with uraemic encephalopathy exhibit provoked seizure activity. Metabolites of creatinine are thought to be proconvulsant as they inhibit gamma-aminobutyric acid (GABA) and stimulate N-methyl-d-aspartate (NMDA) receptors, thus increasing calcium influx into neurones and increasing cortical activity. Electrolyte imbalance is also important in the pathophysiology of seizures in CKD as changes in extracellular ion concentration influence the activity of voltage-gated ion channels.

Dialysis disequilibrium syndrome is a rare form of transient encephalopathy that is usually precipitated by rapid or omitted dialysis sessions. Although the exact cause is unknown, it is thought to be caused by the relatively faster clearance of urea from plasma relative to that from the brain. The association between recombinant human erythropoietin and seizures is uncertain; however, it was once considered a risk factor for seizures. Certain classes of antibiotics can cause cortical irritability and may contribute to seizure development. These include penicillins, cephalosporins, carbapenems and quinolones.

Autonomic neuropathy is common in patients with CKD because of decreased baroreceptor sensitivity, sympathetic overactivity and parasympathetic dysfunction. Blood pressure control may be difficult to achieve, and the patient may be predisposed to the development of perioperative arrhythmias. Uraemia, type 2 diabetes mellitus and hyperparathyroidism all contribute to the pathogenesis of autonomic neuropathy.

Endocrine system

Deterioration in renal function leads to reduced synthesis of the active form of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol). This leads to impaired calcium reabsorption from the gastrointestinal tract and the kidneys. An increase in serum phosphate (from failure of excretion) also contributes to hypocalcaemia, which stimulates production of parathyroid hormone (PTH); over time, parathyroid hyperplasia ensues with pathologically raised PTH levels. This secondary hyperparathyroidism leads to bone demineralisation and a consequent increase in the risk of fractures.

Phosphate retention may necessitate the use of dietary phosphate restriction and phosphate binders. Vitamin D analogues and calcimimetics suppress the secretion of PTH.

Decreased sensitivity to insulin can worsen glycaemic control.¹⁸

Management of CKD

The principles of management around CKD are based on treating reversible causes, preventing or slowing progression of the disease, managing complications and identifying patients requiring RRT.¹⁹

Prevention of AKI and subsequent progression to CKD

Renal hypoperfusion may occur because of hypovolaemia, hypotension or infection. The anaesthetist therefore has an important role in the prevention of AKI in the perioperative period. Stopping nephrotoxic drugs such as aminoglycoside antibiotics, NSAIDs and radiographic contrast should be considered. Relief of urinary tract obstruction may also reverse the disease process.

Slowing the rate of progression

The main targets for renal protection are optimal blood pressure control and control of proteinuria. This is largely achieved using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers. Treatment of hypertension also reduces the rate of cardiovascular complications. The optimal blood pressure target should be individualised, taking into account comorbidities such as diabetes.

Diet plays an important part in slowing the rate of progression in CKD. The recommended daily energy intake is 30–40 kcal kg⁻¹ ideal body weight (IBW) per day with adjustments needed to consider age and physical activity. Nutritional supplementation may be required. The minimum protein intake for a patient with CKD stage 4–5 who is not on dialysis is 0.8 g kg⁻¹ IBW day⁻¹. Sodium intake should be restricted to <2.4 g day⁻¹. Patients with hyperkalaemia, hyperphosphataemia, or both may need to restrict their dietary potassium and phosphate intake, respectively. It is therefore imperative that patients have access to expert advice from a dietitian as part of a multidisciplinary approach.²⁰

Renal replacement therapy

The options for managing end-stage renal failure include conservative management focussed on achieving symptom control, RRT and renal transplantation.

Patients with CKD stage 5 (GFR <15 ml min⁻¹) are usually referred to a nephrologist for discussion regarding further management. There are no absolute criteria for commencement of RRT in this setting and decisions regarding treatment options are made in close collaboration with the patient.

Renal replacement therapy comprises either dialysis, which can be peritoneal dialysis (PD) or haemodialysis, or kidney transplantation.

In PD, the peritoneum is used as the membrane through which fluid and dissolved substances are exchanged with the blood. Dialysate is infused in the peritoneal cavity. This dialysate contains sodium chloride, lactate or bicarbonate and a high concentration of glucose ensuring hyperosmolarity. Proteins and electrolytes are exchanged over the membrane and the exchange of water is driven by osmosis. This is considered a more ‘lifestyle-friendly’ method of RRT and allows patients to be treated at home or in an ambulatory context, and obviates the need for invasive vascular access. It is not without complications, some of which include peritonitis, hyperglycaemia, weight gain, hernias and back pain. Encapsulating peritoneal sclerosis (EPS) is a rare but potentially fatal complication of PD. It occurs because of thickening and sclerosis of the peritoneum, which can cause bowel obstruction.

In haemodialysis, dialysate is pumped in a counter-current direction to blood flow and solutes equilibrate after diffusion across a semipermeable membrane. This too has associated complications, which include those related to vascular access, hypotension, arrhythmias and dysequilibration syndrome.

Kidney transplantation from either a cadaveric or living donor provides the best outcomes and should be considered for all patients with CKD stage 5. At induction of anaesthesia for renal transplantation, patients require antibodies directed against T cells such as basiliximab or alemtuzumab. Transplant recipients also require long-term maintenance immunosuppression to prevent rejection.

A comprehensive overview of RRT modalities is outside the scope of this article, but further information can be found in the referenced text.²¹

Vascular access

Haemodialysis necessitates vascular access, and there are several methods that the anaesthetist should be familiar with.²² The type of vascular access device may be temporary or more permanent depending on clinical need. Temporary vascular access can be achieved by short-term lines, tunnelled and cuffed lines and subcutaneous port catheter systems. Guidance suggests that acute short-term non-cuffed lines should not be used for longer than 1 week because of the risk of infection. The most common site for temporary vascular access is the right internal jugular vein because of its relative ease of access, a lower risk of stenosis than the left internal jugular vein and subclavian routes, and a lower risk of infection than the femoral route.

More permanent vascular access solutions include native arteriovenous fistulae (the vascular access of choice), arteriovenous grafts or long-term catheters.

Complications related to vascular access include infection, stenosis, thrombosis and aneurysm.

Pharmacology

Pharmacokinetics

Absorption

Gastroparesis leads to delayed gastric emptying.²³ Drugs may therefore take longer to reach peak plasma concentrations. Fluid overload can lead to small bowel oedema, which may result in delayed absorption. An increase in gastric pH occurs as a result of the action of gastric urease which converts urea to ammonia. As a result, the degree of drug ionisation is altered and this may affect drug bioavailability.

Distribution

The volume of distribution (V_D) of a drug is influenced by total body water, protein binding and tissue binding. All of these variables are affected by CKD. Protein binding of acidic drugs is reduced as a result of hypoalbuminaemia, conformational changes in protein binding sites and competition for binding sites with organic acids. Conversely, there is an increase in the plasma concentration of alpha₁-acid glycoprotein, which is the main binding site for basic drugs. Hydrophilic drugs exhibit an increase in V_D (and tissue binding) owing to fluid retention in patients with CKD. As the extracellular fluid volume increases, the serum concentration of a given drug may decrease. This should be considered when calculating loading doses in patients with CKD.

Metabolism

Cytochrome P450 (CYP) activity may be altered in the context of severe CKD. The effect is different on different isoenzymes: CYP3A4 and CYP2C9 are inhibited whereas CYP2E1 is induced.

Excretion

Drugs that are normally excreted renally may accumulate. The extent of the accumulation depends on the degree to which the drug is dependent on renal excretion compared with non-renal clearance. Interestingly, non-renal clearance of many drugs is also reduced. Dose changes are required for many drugs in CKD, and creatinine clearance is often used to aid dosage modifications depending on the severity of renal impairment.

Chronic kidney disease and anaesthesia

Preoperative considerations

History and examination

In addition to the general preoperative evaluation, there are specific points of attention in patients with CKD:

• (i)Aetiology of the CKD
• (ii)Severity of renal impairment (clinical and biochemical)
• (iii)Fluid status, dry weight, ability to produce urine
• (iv)Renal replacement therapy: modality, last session, amount of fluid removed
• (v)Drug history, paying particular attention to immunosuppressant and long-term steroid therapy (may require perioperative steroid replacement)

The presence of an arteriovenous fistula should be noted. Repeated attempts at vascular access cause patients with CKD to have thrombosed and fragile vasculature. Invasive vascular access may be required. Capillary refill time, skin turgor and auscultatory findings are a handful of clinical signs that may provide clues regarding the patient's volaemic status.

Clinical investigations

All patients with CKD should have a full blood count and urea and electrolytes measured. The full blood count will reveal anaemia and the biochemistry tests will aid quantification of CKD severity. Coagulation studies can be helpful in patients where coagulopathy is suspected, and there is the potential for perioperative bleeding. However normal coagulation studies do not preclude thrombopathy.

Where there is clinical evidence of fluid overload, a chest X-ray is indicated to visualise pleural effusions. A patient with suspicion of cardiac impairment or pericardial effusion should have echocardiography. All patients should have an ECG to screen for left ventricular hypertrophy, ischaemia and arrythmias.

Preoperative management

Disease-specific treatment should be continued throughout the perioperative period where it is safe and practicable to do so. Certain medications such as ACE inhibitors remain controversial in the preoperative setting with no consensus regarding whether preoperative ACE inhibitor therapy is beneficial or harmful. Therefore, preoperative antihypertensive management should be considered on an individual basis and remains at the discretion of the anaesthetist. Should a patient require dialysis before surgery, liaise with the patient's specialist team.

Conduct of anaesthesia

In addition to the minimum monitoring standards set out by the Association of Anaesthetists, the use of more invasive monitoring should be considered Those patients who have poor blood pressure control before surgery may benefit from the insertion of an arterial line. Prolonged major surgery may also be an indication for invasive arterial pressure monitoring. Central venous access may be required because peripheral venous access is poor, to facilitate the use of potent vasoactive drugs and can aid in assessment of the patient's fluid status. Care should be taken to preserve arteriovenous fistulae and to protect potential fistula sites. As such, forearms veins should be avoided where possible. Arteriovenous fistulae should be carefully wrapped in cotton wool and the non-invasive blood pressure cuff placed on the opposite arm. Urine output monitoring is an important modality in assessing end organ perfusion and is even more valuable in the context of CKD.

Gastroparesis because of autonomic dysfunction may necessitate a rapid sequence induction. A modified approach should be used with rocuronium and sugammadex reversal if required. For intraoperative muscular relaxation, atracurium or cisatracurium are the drugs of choice. In general, drugs with shorter half-lives and drugs that do not depend on renal elimination should be used in order to prevent accumulation.

Inhalational agents

Production of inorganic fluoride from the metabolism of volatile anaesthetics, particularly methoxyflurane, by the hepatic cytochrome P450 system is known to cause vasopressin-resistant high-output renal insufficiency. Animal and human studies have demonstrated that neither the peak value of fluoride nor the duration of systemic fluoride exposure correlate with anaesthetic nephrotoxicity.²⁴

There has been much discussion and research regarding sevoflurane and the production of potentially toxic chemicals (compounds A, B, C, D and E) that are produced when sevoflurane is used in the presence of carbon dioxide absorbents. When sevoflurane encounters soda lime absorbers, it undergoes dehydrofluorination to form haloalkenes (called compound A). Compound A has been shown to be severely nephrotoxic in rats. However, the concentration of these compounds produced in clinical practice is insufficient to induce nephrotoxicity. As such, sevoflurane is considered safe in CKD.

Desflurane and isoflurane are metabolised to a minimal extent and there are no concerns regarding their use in CKD.

Neuromuscular blocking agents

Atracurium is the neuromuscular blocking agent (NMBA) of choice in patients with CKD. Its metabolism is unique. Atracurium undergoes ester hydrolysis and Hofmann degradation, both of which are independent of renal function. Cisatracurium can also be used in patients with CKD. It is predominantly eliminated by Hofmann degradation. Its clearance is reduced by 13% in CKD, and its terminal elimination half-life is increased by 4.2 min. The cis–cis isomer of mivacurium may accumulate and result in slower spontaneous recovery of neuromuscular block. An adjustment in the rate of infusion should be considered. Up to 30% of vecuronium is excreted renally. Therefore, its duration of action is increased, and its clearance is reduced in patients with CKD. Infusions or repeat boluses may accumulate. Up to a third of rocuronium is excreted renally in a 24-h period. Its clearance is reduced by 39% in CKD therefore prolonging time to recovery. The effects of rocuronium become less predictable in renal failure. Pancuronium has reduced clearance and a prolonged half-life in those with CKD and so is best avoided.

Suxamethonium should be avoided because of the risk of exacerbating pre-existing hyperkalaemia.

Sugammadex has been used successfully in clinical research to reverse blockade from aminosteroid NMBAs in patients with severe renal impairment. The sugammadex–rocuronium complex can persist in vivo for up to 7 days. The rocuronium–sugammadex complex is very stable and can be cleared by high-flow dialysis.²⁵

Opioid analgesics

Opioids have no direct nephrotoxic effects. They do have an antidiuretic effect, which may manifest clinically as urinary retention.

The metabolite responsible for the potent analgesic, sedative and respiratory depressant effects of morphine is morphine-6-glucuronide. Its elimination is dependent on renal function, and its half-life is prolonged from 2 to 27 h in patients with CKD. Therefore, an appropriate dose reduction should be considered. Approximately 7% of fentanyl is excreted unchanged in the urine. Its clearance is reduced in CKD. In the context of renal failure, alfentanil is less protein bound and there is therefore a greater amount of free drug available to exert its effect. A dose reduction may be necessary. Remifentanil is not dependent on renal function for its elimination. Both oxycodone and its metabolites accumulate in patients with CKD with a related prolongation in elimination half-life of 2.3–3.9 h. This may necessitate a dose reduction and an increase in dose interval. Tramadol is 30% excreted unchanged in the urine. It may be epileptogenic in the context of uraemia because of the lowered seizure threshold. The elimination half-lives of codeine and dihydrocodeine are significantly prolonged, and these drugs should therefore be used with caution.

Non-steroidal anti-inflammatory drugs

The nephrotoxic potential of NSAIDs is well known, and as such this class of drug should be avoided in the patient with CKD. Such drugs reduce renal blood flow and GFR and may also cause acute interstitial nephritis. They can increase the risk of major vascular events and increase the risk of bleeding in a group of patients who may have an element of coagulopathy because of uraemia and platelet dysfunction. Non-steroidal anti-inflammatory drugs have a harmful effect on potassium excretion and can contribute to hyperkalaemia.

Regional anaesthesia

Regional anaesthesia is a useful way of avoiding systemic drug accumulation and can be used as the primary anaesthetic technique, depending on the type of surgery. Central neuraxial blockade is not absolutely contraindicated, but consequent hypotension must be attended to in order to prevent worsening of renal perfusion and further worsening in renal function. Blood pressure should be maintained with vasoconstrictors and fluid preloading should be carried out judiciously to prevent precipitating fluid overload. Coagulation abnormalities must be borne in mind and might pose a contraindication to spinal or epidural anaesthesia.

Irrespective of the technique and drugs used, it is essential to maintain normovolaemia and renal perfusion pressure. Blood pressure targets should be individualised for the patient using preoperative baseline readings as an estimate.

Careful fluid balance extends to the postoperative period. Patients may require dialysis. Patients with CKD are vulnerable to the sedative effects of opioids amongst other drugs and can take longer to emerge from anaesthesia with more prolonged residual drowsiness. They may therefore require an extended period of supplemental oxygen therapy and continuous oxygen saturation monitoring.

Declaration of interests

The authors declare that they have no conflicts of interest.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Biographies

Samina Chowdhury FRCA is a specialty registrar in anaesthesia in Yorkshire, currently on a fellowship in Canada. Her clinical interests include peri-operative medicine and anaesthesia for the high risk surgical patient.

Hamish McLure FRCA is a consultant anaesthetist and medical director (Professional Standards & Workforce Development) at Leeds Teaching Hospitals NHS Trust. He is past chairman of the Royal College of Anaesthetists' Clinical Director Network. His major clinical interests are anaesthesia for renal transplantation, obstetrics and providing long-term vascular access.

Matrix codes: 1A01, 1A02, 1A03, 2A03, 2A05, 2A07, 3I00