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Renal failure and its treatment
NEPHROLOGY
Renal failure and its treatment
Learning objectives After reading this article you should: C be able to define and classify acute kidney injury, along with understanding the management of acute kidney injury C have an understanding of chronic kidney injury and the comorbidities associated with chronic kidney disease C understand the principles of and the different types of renal replacement therapy
Andrew Martin John MacDonald John Moore
Abstract Kidney disease can be defined as acute or chronic kidney injury. Acute kidney injury is measured directly via glomerular filtration rate and indirectly via urea and electrolyte levels. Acute kidney injury can be classified via the RIFLE criteria. Chronic kidney injury is a progressive and irreversible condition, which is defined as an estimated glomerular filtration rate (eGFR) of less than 60 ml/minute/1.73 m2 or the presence of one or more markers of chronic kidney damage (irrespective of eGFR) on at least two occasions more than 3 months apart. As chronic kidney injury progresses there are a number of co-morbidities associated with the disease process, cardiovascular, respiratory and endocrine. These co-morbidities must be considered when anaesthetizing a patient with kidney injury. Renal replacement therapy may be necessary for patients who acutely deteriorate to end stage renal failure or in those with a slow progression to this point. Haemofiltration or haemodiafiltration may be used in the acute setting and haemodialysis or peritoneal dialysis may be used in cases where the deterioration of renal function takes a more progressive course.
the letters with numbers to indicate severity (stages 1, 2 and 3).1 Outcomes were removed from the staging system. The AKIN defines AKI as an abrupt (within 48 hours) reduction in kidney function, defined as an absolute increase in serum creatinine of at least 0.3 mg/dl (26.4 mmol/litre), or a percentage increase in serum creatinine of at least 50% (1.5 baseline), or a reduction in urine output to 0.5 ml/kg/h our or lower for more than 6 hours (Table 1). Aetiology AKI is classically divided into three categories according to aetiology: pre-renal (volume responsive), renal (intrinsic) and postrenal. Pre-renal AKI results from any cause of renal hypoperfusion leading to a reduction in GFR. Damage to any part of the nephron (glomerulus, tubule, vasculature or interstitium) leads to intrinsic AKI, and obstructed flow of urine at any point downstream from the kidney (ureters, bladder or urethra) leads to post-renal AKI.
Keywords Acute kidney injury; assessment of renal function; chronic kidney disease and anaesthesia; renal failure; renal replacement therapy Royal College of Anaesthetists CPD matrix: 1A01, 2A03, 2C04
Prevalence and outcome AKI is increasingly prevalent amongst hospital patients, occurring in 5e7% of all admissions according to US data. AKI has a high associated mortality: 10% in ward-based patients rising to over 50% for those with AKI in intensive care, although the majority of survivors will have return of normal renal function. The high mortality and morbidity associated with AKI was examined by NCEPOD in the 2009 report ‘Adding Insult to Injury’. This identified sequential deficits in the care of patients with AKI in terms of accurate diagnosis, recognition of the acutely ill patient, senior medical review and treatment of AKI.2
Acute kidney injury Current definition and classification Until 2004, there were no standard criteria for the diagnosis of acute kidney injury (AKI). Following a consensus conference, uniform standards for the diagnosis and staging of acute renal failure (ARF) were proposed by the Acute Dialysis Quality Initiative (ADQI) group using the ‘RIFLE’ classification. The ‘RIFLE’ acronym classified ARF into the three levels of severity (risk, injury and failure) and two outcomes (loss of function and end-stage kidney disease). This was then simplified in 2007 by the Acute Kidney Injury Network (AKIN), adopting the term acute kidney injury (AKI) instead of ARF and replacing
Acute management of AKI Management will depend to a degree on the cause of AKI. In the context of AKI developing as a complication of severe sepsis, major surgery, trauma or major burns; treatment will be in terms of resuscitation using an ABC approach. Oxygenation should be optimized, ventilating as necessary, circulation should be assessed and managed using a combination of invasive monitoring and locally available volume assessment tools [LiDCO, Doppler, Vigileo]. Once adequate fluid loading has taken place using a crystalloid solution, inotropic and vasopressor support should be utilized to achieve an appropriate mean arterial blood pressure (MAP). The target MAP should take into account the patient’s normal blood pressure and any history of hypertension. When AKI occurs out with multi-organ failure, then attention needs to be focused on making a diagnosis and initiating therapies that might reverse the process. Acute kidney injury
Andrew Martin MBChB FRCA MRCP is an ST5 Anaesthesia and Intensive Care Medicine Trainee, North West Deanery, UK. Conflicts of interest: none. John MacDonald MA MBBChir FRCA is an ST5 Anaesthetisia and Intensive Care Medicine Trainee, North West Deanery, UK. Conflicts of interest: none. John Moore BSc MBChB FRCA is a Consultant in Anaesthesia and Critical Care at the Manchester Royal Infirmary, UK. Conflicts of interest: none.
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NEPHROLOGY
Definition and classification CKD is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health.6 From 2004 the UK adopted the US Kidney Disease Outcomes Quality Initiative (KDIGO) definition and classification of CKD. Initially CKD was defined on the basis of an eGFR less than 60 ml/minute/1.73 m2 or evidence of chronic kidney damage (irrespective of eGFR) for more than 3 months. In 2009 the albumin to creatinine ratio (ACR) was incorporated into the definition of CKD such that an ACR of 3 mg/mmol or higher on two occasions more than 3 months apart meant that CKD could be diagnosed in the presence of an eGFR greater than 60 ml/ minute/1.73 m2. The 2013 KDIGO guideline defines CKD as the presence for more than 3 months of an eGFR less than 60 ml/ minute/1.73 m2 or one or more of the following markers of kidney damage: albuminuria (albumin excretion ratio of 30 mg/24 hours; ACR 30 mg/g) urine sediment abnormalities electrolyte and other abnormalities due to tubular disorders abnormalities detected by histology structural abnormalities detected by imaging history of kidney transplantation. CKD is classified on the basis of eGFR and ACR (Table 2). ACR is classified into three groups and eGFR into six, by combining ACR and eGFR values patients can be assigned a risk of developing adverse outcomes related to CKD. This guides further treatment and management of their condition in an attempt to reduce the risk of progression, cardiovascular morbidity and mortality, and late presentation in end stage renal failure. ERF is defined as an eGFR of less than 15 ml/minute/1.73 m2.
Staging of AKI Stage
Serum creatinine
Urine output (ml/kg/hour)
1
1.5e1.9 times baseline OR 0.3 mg/dl (26.5 mmol/litre) increase 2.0e2.9 times baseline
<0.5 for 6e12 hours
2 3
3.0 times baseline OR Increase in serum creatinine to 4.0 mg/dl (353.6 mmol/litre) OR Initiation of renal replacement therapy OR, In patients <18 years, decrease in eGFR to <35 ml/minute/1.73 m2
<0.5 for 12 hours <0.3 for 24 hours OR Anuria for 12 hours
eGFR, estimated glomerular filtration rate.
Table 1
guidelines developed by the Greater Manchester Renal and Critical Care Networks provide an excellent step approach to the management of AKI3 (Figure 1). Acute renal replacement therapy (RRT) should be initiated when life-threatening changes in fluid, electrolyte and acid-base balance exist such as: severe fluid overload pulmonary oedema hyperkalaemia metabolic acidosis acute complications of uraemia.
Prevalence and progression The UK prevalence of stages IIIeV CKD is around 5%, with prevalence increasing with age mainly due to the accumulation of co-morbidities such as hypertension and heart failure. CKD benefits from early recognition, specialist management of the CKD and any associated co-morbidities. ERF is more prevalent in ethnic minority populations owing to the increased prevalence of type 2 diabetes and hypertension.
Detecting AKI earlier As mentioned GFR can be reduced by over 50% before urea and creatinine become abnormal, thus there is much interest in the early detection of AKI. Biomarkers such as neutrophil gelatinaseassociated lipocalin (NGAL) protein, urinary kidney injury molecule-1 (KIM-1) and interleukin (IL)-18 appear useful in detecting injury within 2e6 hours.4 Cystatin C is a small molecule that is freely filtered at the glomerulus but, unlike creatinine, is not secreted by epithelial cells; its concentration has been shown to rise earlier than creatinine in critical care patients with AKI.5 Measurement of renal perfusion using Doppler ultrasound also seems to help determine those who will go on and develop AKI. Ultimately a matrix of biomarkers and imaging in combination may better guide AKI management.
Complications of chronic kidney disease Cardiovascular disease Premature cardiovascular disease is the main cause of death in patients with CKD, accounting for almost half of all-cause mortality in ERF. The risk of cardiovascular events rises significantly below an eGFR of 60 and increases progressively with declining renal function. The actual diagnosis of AMI can be difficult as ECG abnormalities are common and cardiac troponins are raised even in the absence of ischaemia. Cardiomyopathy is common in patients with CKD. Left ventricular (LV) hypertrophy results from hypertension and arteriosclerosis. Anaemia, fluid overload and arteriovenous fistulae cause volume overload resulting in LV dilation. These changes in LV structure and the associated coronary artery disease lead to systolic and diastolic dysfunction. Mitral and aortic valve calcification occurs commonly as a result of metastatic calcium deposition, with
Chronic renal failure Chronic kidney disease (CKD) is a progressive, irreversible process. The precise aetiology is often uncertain, but diabetes is the commonest cause of established renal failure (ESRF) in those starting dialysis. Hypertension, glomerulonephritis and pyelonephritis are less frequent causes. The presence of CKD is associated with an increased mortality risk.
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NEPHROLOGY
Figure 1
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NEPHROLOGY
patients with CKD had an increased incidence of blood-borne viruses due to recurrent blood transfusions prior to screening of the donor population. CKD is associated with an increased tendency to bleed, related to defective platelet adhesion and aggregation. Factors involved include an intrinsic platelet defect, abnormal von Willebrand factor (vWF) binding and increased parathyroid hormone levels. Platelet count and coagulation tests are generally normal, although bleeding time may be prolonged. Correction of anaemia, increasing vWF levels with desmopressin or cryoprecipitate, and haemodialysis (HD) are useful interventions to help reduce bleeding tendency.
secondary valvular dysfunction and conduction abnormalities. Infective endocarditis is more common in patients with CKD as a result of these valvular abnormalities and immunosuppression. Pericarditis associated with chronic pericardial effusions and tamponade can rarely occur in patients with end stage renal disease. Hypertension Hypertension is extremely common in CKD, not only as a primer for the development of CKD, but also as a feature of disease progression with inadequate excretion of salt and water and increased renin production. Treatment to a level below 140/90 mm Hg is recommended to help reduce progression of CKD and the associated cardiovascular risk. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker drugs have an additional renal protective effect related to a reduction in proteinuria.
Immune function Altered immune function is common in patients with renal failure. Suppression of T cell and humoral mediated immunity, an increase in pro-inflammatory cytokines, caused by uraemic immune dysfunction. Superficial infections are common, particularly in proximity to fistula sites and invasive lines. Postoperatively wound healing can be poor, with an increased frequency of wound infections.
Haematological CKD-associated anaemia is normocytic and normochromic and associated with uraemia which reduces red blood cell life span. Erythropoietin-stimulating agents are generally used in those with a haemoglobin lower than 11 g/dl. Blood transfusion is avoided where possible due to the risk of fluid overload and of sensitization to donor lymphocytes which may make donor kidney compatibility more difficult in the future. Historically
Gastrointestinal tract Malnutrition and anorexia occur frequently in patients with CKD. Poor appetite is worsened by nausea and vomiting through
Classification of chronic kidney disease
Table 2
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NEPHROLOGY
those with normal renal function and those with ESRF has shown Sugammadex to be safe, with no difference in its ability to reverse rocuronium.6
uraemia and delayed gastric emptying due to autonomic dysfunction. Gastric mucosal irritation is common as is peptic ulcer disease along with an increased frequency of gastrointestinal bleeding.
Monitoring Care should be taken to prevent damage to fistula sites, with padding and clear identification so as to avoid its inadvertent use for cannulation and blood pressure measurement. Peripheral venous access is often difficult and ultrasound may be useful. Central lines may be necessary and should be considered when large fluid shifts are anticipated or where close fluid monitoring is required. Locally available volume assessment tools (LiDCO, Doppler, Vigileo) can also be very useful to guide intraoperative fluid administration. Use of arterial lines should be reserved for only when they are clinically essential, due to the potential damage to future fistula sites.
Neurological Patients with CKD are at an increased risk of both CNS and peripheral nervous system (PNS) abnormalities. CNS abnormalities may manifest as a change in behaviour, muscle tone, encephalopathy or seizures. Dialysis disequilibrium syndrome can occur with patients on dialysis and is characterized by focal neurological changes or loss of consciousness due to rapid solute removal resulting in cerebral oedema. Peripheral neuropathy is more common in patients with CKD and is associated with autonomic neuropathy. Endocrine Patients with CKD can develop secondary hyperparathyroidism due to decreased phosphate excretion by the diseased kidney and decreased gastrointestinal absorption of calcium as a consequence of reduced hydroxylation of vitamin D. This may develop into tertiary hyperparathyroidism and hypercalcaemia in renal transplant patients.
Drug handling and pharmacology Drug handling in CKD can be significantly altered. Delayed gastric emptying may reduce drug absorption. Altered levels of total body water, plasma protein binding and tissue binding will also have an effect. Hypoalbuminaemia and acidosis can increase the availability of higher protein bound drugs. Drugs that are renally excreted or metabolized will have an altered pharmacokinetic profile (Table 3).
Metabolic In patients with end stage renal disease chronic metabolic acidosis can occur. This is due to the reduced ability of the diseased kidney to regenerate bicarbonate as well as buffer and excrete excess protons.
Regional anaesthesia Peripheral nerve blocks and local anaesthetic infusion techniques are being increasingly used, due to their opiate-sparing properties in patients with renal failure. Local anaesthetics are safe to use, but the dose should be reduced by 25% due to reduced protein binding and a reduction in seizure threshold.7 Adjuncts such a clonidine can be added to the nerve block with the aim of increasing the analgesic duration of the peripheral nerve block. Neuroaxial anaesthesia can be beneficial to patients with CKD. However, coagulopathies are more common, so a risk ebenefit assessment should be carried out, taking account of any evidence of coagulopathy or platelet dysfunction.
General anaesthesia in CKD Patients with CKD may require general anaesthesia, for routine or emergency operations, insertion of fistulas for dialysis and for renal transplantation. As discussed, patients with CKD have a number of co-morbidities, along with an increased risk of mortality, so specific perioperative planning is necessary. Premedication with opioids or sedatives should be avoided due to the altered pharmacokinetics in patients with CKD. An H2antagonist or metoclopramide may be considered if a rapid sequence induction is planned. Anti-hypertensives should be continued. A plan should be made for post-operative care, with a destination arranged. Often, this may require transfer from theatre to the critical care unit for fluid balance monitoring or on-going renal replacement therapy.
Low-molecular-weight heparin (LMWH) The administration of LMWH is an integral part of modern hospital practice. A detailed assessment of thromboprophylaxis risk should be carried out in all patients. Patients with CKD will have a secondary reduced clearance of LMWH and generally benefit from a reduced dose and factor Xa monitoring.
Airway management With the increased risk of gastro-oesphageal reflux disease and delayed gastric emptying in CKD, there is increased risk of reflux and aspiration at induction. There is also an increased frequency of difficult intubation and airway management with CKD, particularly in those with diabetes. These factors together may necessitate the need for a rapid sequence induction. The recent introduction of Sugammadex has meant that suxamethonium use, with its risk of hyperkalaemia in patients with CKD, has regressed. Sugammadex is a modified cyclodextrin, developed for the rapid reversal of rocuronium, a muscle relaxant that normally accumulates in renal dysfunction. A trial comparing its use in
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Renal replacement therapies RRT may be necessary acutely for the management of AKI or for CKD when a patient who has degenerated acutely into ESRF. For AKI in the critical care setting8, patients generally receive (in the UK, Europe and Australia) continuous renal replacement therapy (CRRT) such as haemofiltration and haemodiafiltration (Figure 2), then going on to HD when more stable. For those patients managed by the hospital’s nephrology team, they will generally receive intermittent HD. Support for more gradual deterioration into ESRF, will either take the form of HD or peritoneal dialysis (PD). This imposes a
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NEPHROLOGY
semipermeable membranes. The membrane may be synthetic, as with haemofiltration and HD membranes, or the patient’s own, as with PD. Modern artificial membranes are highly efficient and maximize water and waste removal with high membrane permeability and large pore size (50 kDa).
Anaesthetic pharmacology in relation to renal failure
Induction agents Propofol Thiopentone Benzodiazepines Muscle relaxants Suxamethonium
Atracurium and Cisatracurium Rocuronium
Analgesics NSAIDS Opiates Morphine
Pethidine
Alfentanil Fentanyl Remifentanil
Inhalation agents
No interaction, safe to use in renal failure Reduction in dose of 30e50% is advised Reduction in dose of 30e50% is advised
Convection and diffusion Solute transfer across the membrane occurs by either convection or diffusion. Convection is the process by which solutes are moved under pressure across a membrane. A positive pressure is created on the blood side of the membrane relative to the dialysate compartment. The resulting pressure gradient is the driving force for filtration in which plasma water is filtered through the membrane producing the ultrafiltrate. Solutes which are small enough to cross the membrane, are then dragged across it by this moving stream of ultrafiltrate. Diffusion is the process where substances flow from compartments where their concentration is higher to those where their concentration is lower. The rate of redistribution depends upon the concentration gradient. Diffusion of a solute across a membrane is called dialysis. Diffusion ceases when equilibrium of solute concentration across the membrane is achieved.
Caution due to precipitant hyperkalaemia. If it is used there will be no alteration in action. Acceptable to use due to ester hydrolysis and hoffmann elimination. Accumulation can occur due to renal excretion, leading to a prolonged NMB. Simple analgesics, following the WHO analgesic ladder Should be avoided in renal failure
Active metabolite morphine-6-gluconoride, potent respiratory depressant and analgesic. Renal excreted, therefore will accumulate in renal failure. Active metabolite norpethidine, is renal excreted, accumulation may precipitate seizures Safe to use. Inactive metabolites Safe to use. Inactive metabolite, which is renally excreted. Plasma and tissue esterase activity is not affected by renal failure. Therefore, they are safe to use in renal failure.
Haemofiltration Haemofiltration is a veno-venous technique using a dual lumen catheter to facilitate convection across a semipermeable membrane to remove water and solutes. Convection is not efficient and therefore requires hourly ultrafiltration rates of 1e2 litres to help achieve urea clearance. The volume of ultrafiltrate produced is replaced, in part or completely, by infusing buffered replacement fluids. Reducing the volume returned to the patient results in net fluid removal. The replacement fluid generally consists of a balanced electrolyte solution, which is either bicarbonate or lactate based. These solutions are added into the circuit before the haemofilter termed pre-dilution, after the filter termed post-dilution, but is most commonly on both sides of the filter. Pre-dilution dilutes the blood that is filtered, so prolonging the circuit life span by decreasing the clotting risk. However, this is inefficient for urea clearance. Increasing post-dilution administration leads to a greater urea clearance.
Safe to use in renal failure. Concern has been raised regarding the use of sevoflurane, due to the decreased excretion of fluoride ions, which may accumulate and worsen renal failure. Further, its metabolite Compound A production has been shown to be nephrotoxic in rats, but no clinical effect is seen in humans
Haemodialysis HD is a process in which diffusion across a semipermeable membrane is used to remove solutes. The patient’s blood is pumped past one side of the membrane, while dialysate fluid of a differing concentration is infused on the other. The concentration gradient created allows waste molecules to diffuse from the plasma into the dialysate fluid. Counter-current flow of the blood and dialysate fluid across the membrane prevents the achievement of equilibrium, maintaining the concentration gradient for diffusion. HD can be continuous, but is mostly intermittent in the setting of ESRF or in the stable patient with AKI.
Table 3
large burden on the patient’s and family’s lifestyle, with regular attendance at hospital required for RRT. However there have been tremendous efforts to move RRT out of hospital and to facilitate patients and their families doing their PD, and more recently, HD at home. For patients on chronic RRT, renal transplantation offers improved survival, better quality of life and is cost-effective in health economic terms. It may be either a cadaveric transplant or increasingly a kidney donated from a living relative.
Haemodiafiltration Haemodiafiltration combines dialysis with the filtration process, to remove water and waste products. Through the process of making diffusion and convection occur simultaneously, the
Mimicking the kidney The kidneys normally remove excess water and waste products through filtration. RRT mimics this action through the use of
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NEPHROLOGY
Components and function of a veno-venous haemodiafiltration circuit Circuit pressure monitors
Dialysate infusion Dual lumen venous catheter
Air and clot trap Haemofilter
Air detector Clamp
Heparin infusion
Ultrafiltration collection bag
Roller pump Replacement fluid infusion Reproduced from Murphy T, Robinson S. Anaesthesia and Intensive Care Medicine 2006;7:247
Figure 2
efficiency and speed of waste (urea) clearance is increased. The fluid used for dialysis and fluid replacement is the same and so a large amount is required.
patient body habitus, clinical condition, coagulopathic status and the site of other lines. The use of ultrasound is recommended when placing any CVC to improve patient safety. The artificial membranes used in RRT circuits are biocompatible materials (cellulose, polysulfone or methylmethacrylate). Despite being biocompatible, on exposure of blood to the foreign material, platelets and the intrinsic and extrinsic clotting cascade are both activated. Thus, anticoagulation is required to prevent thrombus formation and malfunction of the circuit. Anticoagulation is not recommended in the presence of an increased bleeding risk or impaired coagulation. Anticoagulation may be achieved via one of three methods. The most commonly used anticoagulant is unfractionated heparin, aiming to maintain an activated partial thromboplastin time ratio 1.5e2.5 times normal. This is particularly useful in acute RRT scenarios. Complications include bleeding and heparin-induced thrombocytopenia. LMWHs, despite having a more consistent bioavailability and being less likely to promote heparin-induced thrombocytopenia, are rarely used. There is no reliable reversal agent and a non-routine test is needed to monitor action (anti-factor Xa). Prostacyclin (prostglandin I2) provides a useful alternative anticoagulant, through its inhibitory effect on platelet reactivity and aggregation. Adverse effects include vasodilation and reversal of hypoxic pulmonary vasoconstriction, potentially exacerbating hypoxaemia. Citrate is as an ideal anticoagulant providing regional anticoagulation of the extracorporeal circuit without the need for systemic anticoagulation. Citrate forms a complex with calcium, preventing its role in the generation of thrombin and secondary clotting. Citrate reaching the systemic circulation is metabolized by the liver, muscle and kidney. Calcium levels must be monitored in the patient during use (risk of hypocalcaemia), as the
Slow continuous ultrafiltration This is a haemofiltration technique used mainly for fluid removal in overloaded patients. No dialysate or replacement fluids are used and the ultrafiltrate that is generated corresponds to weight loss. The fluid removed is regulated to produce a slow continuous plasma water loss, normally when a patient has proven resistant to diuretics. Peritoneal dialysis Dialysis fluid is inserted into the peritoneal cavity via a surgically inserted catheter. The peritoneum then acts as a semipermeable membrane, between the blood in the capillaries and the fluid. Through the tonicity gradient created by the dialysate, fluid solute and water movement is achieved. After a period of equilibration, the dialysate fluid is removed. The process may be continuous or intermittent and is used mainly for home dialysis. Fluid removal is not as good as other forms of RRT and it tends to be used in the early stages of RRT. Access and anticoagulation Acute RRT through CRRT or HD will be via a dual lumen central venous catheter (CVC). Patients on long-term RRT for ESRF will usually have a surgically created arteriovenous fistula for HD, or a peritoneal catheter for PD. A number will continue on HD via a long-term CVC. Catheters are polyurethane, being stiff for insertion and avoiding collapse at high negative pressures. Longterm catheters may be tunnelled to reduce infection risk. Sites of CVC placement include the commonly used internal jugular or femoral veins. The subclavian vein may also be used. Decision on placement sites will involve the assessment of the
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2 NCEPOD. ‘Adding Insult to Injury’. A review of the care of patients who died in hospital with a primary diagnosis of acute kidney injury. 2009, http://www.ncepod.org.uk/2009report1/Downloads/AKI_report.pdf. 3 Challiner Rachael, Szeki Iren. Greater Manchester Renal Network and Greater Manchester Critical Care Network. Acute Kidney Injury Guidelines 2010. 4 Parikh CR, Devarajan P. New biomarkers of acute kidney injury. Crit Care Med 2008 Apr; 36(4 suppl): S159e65. 5 Villa P, Jimenez M, Soriano MC, et al. Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients. Crit Care 2005; 9: R139e43. 6 Kidney Disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 2013;(suppl 3); 1e150. 7 Gentz BA, Malan Jr TP. Renal toxicity with sevoflurane: a storm in a teacup? Drugs 2001; 61(15): 2155e62. 8 Standards and recommendations for the provision of RRT on ITUs in the UK Intensive Care Society Standards and Safety 2009.
circuit filters the citrate complex. Liver failure is a contraindication to use. It is expensive and requires adherence to a strict protocol, but the cost is offset by the improved life span of CVVF circuits and the possibility that it may improve survival. Further advantages include a reduced risk of bleeding in the patient. It is suggested as an option for patients undergoing CRRT. Lastly, although not an anticoagulant, alterations in the ratio of pre-dilution to post-dilution may also affect clotting within the circuit. Increasing pre-dilution flows reduces haematocrit levels, reducing the tendency for clot formation. However, this reduces the filtration fraction, reducing the efficiency of the circuit. Often a balance may be achieved depending on the individual circumstances of the patient. A REFERENCES 1 Mehta RL, Kellum JA, Shah SV, et al. Acute kidney injury network. Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31.
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Renal failure and its treatment
Learning objectives After reading this article you should: C be able to define and classify acute kidney injury, along with understanding the management of acute kidney injury C have an understanding of chronic kidney injury and the comorbidities associated with chronic kidney disease C understand the principles of and the different types of renal replacement therapy
Andrew Martin John MacDonald John Moore
Abstract Kidney disease can be defined as acute or chronic kidney injury. Acute kidney injury is measured directly via glomerular filtration rate and indirectly via urea and electrolyte levels. Acute kidney injury can be classified via the RIFLE criteria. Chronic kidney injury is a progressive and irreversible condition, which is defined as an estimated glomerular filtration rate (eGFR) of less than 60 ml/minute/1.73 m2 or the presence of one or more markers of chronic kidney damage (irrespective of eGFR) on at least two occasions more than 3 months apart. As chronic kidney injury progresses there are a number of co-morbidities associated with the disease process, cardiovascular, respiratory and endocrine. These co-morbidities must be considered when anaesthetizing a patient with kidney injury. Renal replacement therapy may be necessary for patients who acutely deteriorate to end stage renal failure or in those with a slow progression to this point. Haemofiltration or haemodiafiltration may be used in the acute setting and haemodialysis or peritoneal dialysis may be used in cases where the deterioration of renal function takes a more progressive course.
the letters with numbers to indicate severity (stages 1, 2 and 3).1 Outcomes were removed from the staging system. The AKIN defines AKI as an abrupt (within 48 hours) reduction in kidney function, defined as an absolute increase in serum creatinine of at least 0.3 mg/dl (26.4 mmol/litre), or a percentage increase in serum creatinine of at least 50% (1.5 baseline), or a reduction in urine output to 0.5 ml/kg/h our or lower for more than 6 hours (Table 1). Aetiology AKI is classically divided into three categories according to aetiology: pre-renal (volume responsive), renal (intrinsic) and postrenal. Pre-renal AKI results from any cause of renal hypoperfusion leading to a reduction in GFR. Damage to any part of the nephron (glomerulus, tubule, vasculature or interstitium) leads to intrinsic AKI, and obstructed flow of urine at any point downstream from the kidney (ureters, bladder or urethra) leads to post-renal AKI.
Keywords Acute kidney injury; assessment of renal function; chronic kidney disease and anaesthesia; renal failure; renal replacement therapy Royal College of Anaesthetists CPD matrix: 1A01, 2A03, 2C04
Prevalence and outcome AKI is increasingly prevalent amongst hospital patients, occurring in 5e7% of all admissions according to US data. AKI has a high associated mortality: 10% in ward-based patients rising to over 50% for those with AKI in intensive care, although the majority of survivors will have return of normal renal function. The high mortality and morbidity associated with AKI was examined by NCEPOD in the 2009 report ‘Adding Insult to Injury’. This identified sequential deficits in the care of patients with AKI in terms of accurate diagnosis, recognition of the acutely ill patient, senior medical review and treatment of AKI.2
Acute kidney injury Current definition and classification Until 2004, there were no standard criteria for the diagnosis of acute kidney injury (AKI). Following a consensus conference, uniform standards for the diagnosis and staging of acute renal failure (ARF) were proposed by the Acute Dialysis Quality Initiative (ADQI) group using the ‘RIFLE’ classification. The ‘RIFLE’ acronym classified ARF into the three levels of severity (risk, injury and failure) and two outcomes (loss of function and end-stage kidney disease). This was then simplified in 2007 by the Acute Kidney Injury Network (AKIN), adopting the term acute kidney injury (AKI) instead of ARF and replacing
Acute management of AKI Management will depend to a degree on the cause of AKI. In the context of AKI developing as a complication of severe sepsis, major surgery, trauma or major burns; treatment will be in terms of resuscitation using an ABC approach. Oxygenation should be optimized, ventilating as necessary, circulation should be assessed and managed using a combination of invasive monitoring and locally available volume assessment tools [LiDCO, Doppler, Vigileo]. Once adequate fluid loading has taken place using a crystalloid solution, inotropic and vasopressor support should be utilized to achieve an appropriate mean arterial blood pressure (MAP). The target MAP should take into account the patient’s normal blood pressure and any history of hypertension. When AKI occurs out with multi-organ failure, then attention needs to be focused on making a diagnosis and initiating therapies that might reverse the process. Acute kidney injury
Andrew Martin MBChB FRCA MRCP is an ST5 Anaesthesia and Intensive Care Medicine Trainee, North West Deanery, UK. Conflicts of interest: none. John MacDonald MA MBBChir FRCA is an ST5 Anaesthetisia and Intensive Care Medicine Trainee, North West Deanery, UK. Conflicts of interest: none. John Moore BSc MBChB FRCA is a Consultant in Anaesthesia and Critical Care at the Manchester Royal Infirmary, UK. Conflicts of interest: none.
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Definition and classification CKD is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health.6 From 2004 the UK adopted the US Kidney Disease Outcomes Quality Initiative (KDIGO) definition and classification of CKD. Initially CKD was defined on the basis of an eGFR less than 60 ml/minute/1.73 m2 or evidence of chronic kidney damage (irrespective of eGFR) for more than 3 months. In 2009 the albumin to creatinine ratio (ACR) was incorporated into the definition of CKD such that an ACR of 3 mg/mmol or higher on two occasions more than 3 months apart meant that CKD could be diagnosed in the presence of an eGFR greater than 60 ml/ minute/1.73 m2. The 2013 KDIGO guideline defines CKD as the presence for more than 3 months of an eGFR less than 60 ml/ minute/1.73 m2 or one or more of the following markers of kidney damage: albuminuria (albumin excretion ratio of 30 mg/24 hours; ACR 30 mg/g) urine sediment abnormalities electrolyte and other abnormalities due to tubular disorders abnormalities detected by histology structural abnormalities detected by imaging history of kidney transplantation. CKD is classified on the basis of eGFR and ACR (Table 2). ACR is classified into three groups and eGFR into six, by combining ACR and eGFR values patients can be assigned a risk of developing adverse outcomes related to CKD. This guides further treatment and management of their condition in an attempt to reduce the risk of progression, cardiovascular morbidity and mortality, and late presentation in end stage renal failure. ERF is defined as an eGFR of less than 15 ml/minute/1.73 m2.
Staging of AKI Stage
Serum creatinine
Urine output (ml/kg/hour)
1
1.5e1.9 times baseline OR 0.3 mg/dl (26.5 mmol/litre) increase 2.0e2.9 times baseline
<0.5 for 6e12 hours
2 3
3.0 times baseline OR Increase in serum creatinine to 4.0 mg/dl (353.6 mmol/litre) OR Initiation of renal replacement therapy OR, In patients <18 years, decrease in eGFR to <35 ml/minute/1.73 m2
<0.5 for 12 hours <0.3 for 24 hours OR Anuria for 12 hours
eGFR, estimated glomerular filtration rate.
Table 1
guidelines developed by the Greater Manchester Renal and Critical Care Networks provide an excellent step approach to the management of AKI3 (Figure 1). Acute renal replacement therapy (RRT) should be initiated when life-threatening changes in fluid, electrolyte and acid-base balance exist such as: severe fluid overload pulmonary oedema hyperkalaemia metabolic acidosis acute complications of uraemia.
Prevalence and progression The UK prevalence of stages IIIeV CKD is around 5%, with prevalence increasing with age mainly due to the accumulation of co-morbidities such as hypertension and heart failure. CKD benefits from early recognition, specialist management of the CKD and any associated co-morbidities. ERF is more prevalent in ethnic minority populations owing to the increased prevalence of type 2 diabetes and hypertension.
Detecting AKI earlier As mentioned GFR can be reduced by over 50% before urea and creatinine become abnormal, thus there is much interest in the early detection of AKI. Biomarkers such as neutrophil gelatinaseassociated lipocalin (NGAL) protein, urinary kidney injury molecule-1 (KIM-1) and interleukin (IL)-18 appear useful in detecting injury within 2e6 hours.4 Cystatin C is a small molecule that is freely filtered at the glomerulus but, unlike creatinine, is not secreted by epithelial cells; its concentration has been shown to rise earlier than creatinine in critical care patients with AKI.5 Measurement of renal perfusion using Doppler ultrasound also seems to help determine those who will go on and develop AKI. Ultimately a matrix of biomarkers and imaging in combination may better guide AKI management.
Complications of chronic kidney disease Cardiovascular disease Premature cardiovascular disease is the main cause of death in patients with CKD, accounting for almost half of all-cause mortality in ERF. The risk of cardiovascular events rises significantly below an eGFR of 60 and increases progressively with declining renal function. The actual diagnosis of AMI can be difficult as ECG abnormalities are common and cardiac troponins are raised even in the absence of ischaemia. Cardiomyopathy is common in patients with CKD. Left ventricular (LV) hypertrophy results from hypertension and arteriosclerosis. Anaemia, fluid overload and arteriovenous fistulae cause volume overload resulting in LV dilation. These changes in LV structure and the associated coronary artery disease lead to systolic and diastolic dysfunction. Mitral and aortic valve calcification occurs commonly as a result of metastatic calcium deposition, with
Chronic renal failure Chronic kidney disease (CKD) is a progressive, irreversible process. The precise aetiology is often uncertain, but diabetes is the commonest cause of established renal failure (ESRF) in those starting dialysis. Hypertension, glomerulonephritis and pyelonephritis are less frequent causes. The presence of CKD is associated with an increased mortality risk.
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Figure 1
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patients with CKD had an increased incidence of blood-borne viruses due to recurrent blood transfusions prior to screening of the donor population. CKD is associated with an increased tendency to bleed, related to defective platelet adhesion and aggregation. Factors involved include an intrinsic platelet defect, abnormal von Willebrand factor (vWF) binding and increased parathyroid hormone levels. Platelet count and coagulation tests are generally normal, although bleeding time may be prolonged. Correction of anaemia, increasing vWF levels with desmopressin or cryoprecipitate, and haemodialysis (HD) are useful interventions to help reduce bleeding tendency.
secondary valvular dysfunction and conduction abnormalities. Infective endocarditis is more common in patients with CKD as a result of these valvular abnormalities and immunosuppression. Pericarditis associated with chronic pericardial effusions and tamponade can rarely occur in patients with end stage renal disease. Hypertension Hypertension is extremely common in CKD, not only as a primer for the development of CKD, but also as a feature of disease progression with inadequate excretion of salt and water and increased renin production. Treatment to a level below 140/90 mm Hg is recommended to help reduce progression of CKD and the associated cardiovascular risk. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker drugs have an additional renal protective effect related to a reduction in proteinuria.
Immune function Altered immune function is common in patients with renal failure. Suppression of T cell and humoral mediated immunity, an increase in pro-inflammatory cytokines, caused by uraemic immune dysfunction. Superficial infections are common, particularly in proximity to fistula sites and invasive lines. Postoperatively wound healing can be poor, with an increased frequency of wound infections.
Haematological CKD-associated anaemia is normocytic and normochromic and associated with uraemia which reduces red blood cell life span. Erythropoietin-stimulating agents are generally used in those with a haemoglobin lower than 11 g/dl. Blood transfusion is avoided where possible due to the risk of fluid overload and of sensitization to donor lymphocytes which may make donor kidney compatibility more difficult in the future. Historically
Gastrointestinal tract Malnutrition and anorexia occur frequently in patients with CKD. Poor appetite is worsened by nausea and vomiting through
Classification of chronic kidney disease
Table 2
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those with normal renal function and those with ESRF has shown Sugammadex to be safe, with no difference in its ability to reverse rocuronium.6
uraemia and delayed gastric emptying due to autonomic dysfunction. Gastric mucosal irritation is common as is peptic ulcer disease along with an increased frequency of gastrointestinal bleeding.
Monitoring Care should be taken to prevent damage to fistula sites, with padding and clear identification so as to avoid its inadvertent use for cannulation and blood pressure measurement. Peripheral venous access is often difficult and ultrasound may be useful. Central lines may be necessary and should be considered when large fluid shifts are anticipated or where close fluid monitoring is required. Locally available volume assessment tools (LiDCO, Doppler, Vigileo) can also be very useful to guide intraoperative fluid administration. Use of arterial lines should be reserved for only when they are clinically essential, due to the potential damage to future fistula sites.
Neurological Patients with CKD are at an increased risk of both CNS and peripheral nervous system (PNS) abnormalities. CNS abnormalities may manifest as a change in behaviour, muscle tone, encephalopathy or seizures. Dialysis disequilibrium syndrome can occur with patients on dialysis and is characterized by focal neurological changes or loss of consciousness due to rapid solute removal resulting in cerebral oedema. Peripheral neuropathy is more common in patients with CKD and is associated with autonomic neuropathy. Endocrine Patients with CKD can develop secondary hyperparathyroidism due to decreased phosphate excretion by the diseased kidney and decreased gastrointestinal absorption of calcium as a consequence of reduced hydroxylation of vitamin D. This may develop into tertiary hyperparathyroidism and hypercalcaemia in renal transplant patients.
Drug handling and pharmacology Drug handling in CKD can be significantly altered. Delayed gastric emptying may reduce drug absorption. Altered levels of total body water, plasma protein binding and tissue binding will also have an effect. Hypoalbuminaemia and acidosis can increase the availability of higher protein bound drugs. Drugs that are renally excreted or metabolized will have an altered pharmacokinetic profile (Table 3).
Metabolic In patients with end stage renal disease chronic metabolic acidosis can occur. This is due to the reduced ability of the diseased kidney to regenerate bicarbonate as well as buffer and excrete excess protons.
Regional anaesthesia Peripheral nerve blocks and local anaesthetic infusion techniques are being increasingly used, due to their opiate-sparing properties in patients with renal failure. Local anaesthetics are safe to use, but the dose should be reduced by 25% due to reduced protein binding and a reduction in seizure threshold.7 Adjuncts such a clonidine can be added to the nerve block with the aim of increasing the analgesic duration of the peripheral nerve block. Neuroaxial anaesthesia can be beneficial to patients with CKD. However, coagulopathies are more common, so a risk ebenefit assessment should be carried out, taking account of any evidence of coagulopathy or platelet dysfunction.
General anaesthesia in CKD Patients with CKD may require general anaesthesia, for routine or emergency operations, insertion of fistulas for dialysis and for renal transplantation. As discussed, patients with CKD have a number of co-morbidities, along with an increased risk of mortality, so specific perioperative planning is necessary. Premedication with opioids or sedatives should be avoided due to the altered pharmacokinetics in patients with CKD. An H2antagonist or metoclopramide may be considered if a rapid sequence induction is planned. Anti-hypertensives should be continued. A plan should be made for post-operative care, with a destination arranged. Often, this may require transfer from theatre to the critical care unit for fluid balance monitoring or on-going renal replacement therapy.
Low-molecular-weight heparin (LMWH) The administration of LMWH is an integral part of modern hospital practice. A detailed assessment of thromboprophylaxis risk should be carried out in all patients. Patients with CKD will have a secondary reduced clearance of LMWH and generally benefit from a reduced dose and factor Xa monitoring.
Airway management With the increased risk of gastro-oesphageal reflux disease and delayed gastric emptying in CKD, there is increased risk of reflux and aspiration at induction. There is also an increased frequency of difficult intubation and airway management with CKD, particularly in those with diabetes. These factors together may necessitate the need for a rapid sequence induction. The recent introduction of Sugammadex has meant that suxamethonium use, with its risk of hyperkalaemia in patients with CKD, has regressed. Sugammadex is a modified cyclodextrin, developed for the rapid reversal of rocuronium, a muscle relaxant that normally accumulates in renal dysfunction. A trial comparing its use in
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Renal replacement therapies RRT may be necessary acutely for the management of AKI or for CKD when a patient who has degenerated acutely into ESRF. For AKI in the critical care setting8, patients generally receive (in the UK, Europe and Australia) continuous renal replacement therapy (CRRT) such as haemofiltration and haemodiafiltration (Figure 2), then going on to HD when more stable. For those patients managed by the hospital’s nephrology team, they will generally receive intermittent HD. Support for more gradual deterioration into ESRF, will either take the form of HD or peritoneal dialysis (PD). This imposes a
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semipermeable membranes. The membrane may be synthetic, as with haemofiltration and HD membranes, or the patient’s own, as with PD. Modern artificial membranes are highly efficient and maximize water and waste removal with high membrane permeability and large pore size (50 kDa).
Anaesthetic pharmacology in relation to renal failure
Induction agents Propofol Thiopentone Benzodiazepines Muscle relaxants Suxamethonium
Atracurium and Cisatracurium Rocuronium
Analgesics NSAIDS Opiates Morphine
Pethidine
Alfentanil Fentanyl Remifentanil
Inhalation agents
No interaction, safe to use in renal failure Reduction in dose of 30e50% is advised Reduction in dose of 30e50% is advised
Convection and diffusion Solute transfer across the membrane occurs by either convection or diffusion. Convection is the process by which solutes are moved under pressure across a membrane. A positive pressure is created on the blood side of the membrane relative to the dialysate compartment. The resulting pressure gradient is the driving force for filtration in which plasma water is filtered through the membrane producing the ultrafiltrate. Solutes which are small enough to cross the membrane, are then dragged across it by this moving stream of ultrafiltrate. Diffusion is the process where substances flow from compartments where their concentration is higher to those where their concentration is lower. The rate of redistribution depends upon the concentration gradient. Diffusion of a solute across a membrane is called dialysis. Diffusion ceases when equilibrium of solute concentration across the membrane is achieved.
Caution due to precipitant hyperkalaemia. If it is used there will be no alteration in action. Acceptable to use due to ester hydrolysis and hoffmann elimination. Accumulation can occur due to renal excretion, leading to a prolonged NMB. Simple analgesics, following the WHO analgesic ladder Should be avoided in renal failure
Active metabolite morphine-6-gluconoride, potent respiratory depressant and analgesic. Renal excreted, therefore will accumulate in renal failure. Active metabolite norpethidine, is renal excreted, accumulation may precipitate seizures Safe to use. Inactive metabolites Safe to use. Inactive metabolite, which is renally excreted. Plasma and tissue esterase activity is not affected by renal failure. Therefore, they are safe to use in renal failure.
Haemofiltration Haemofiltration is a veno-venous technique using a dual lumen catheter to facilitate convection across a semipermeable membrane to remove water and solutes. Convection is not efficient and therefore requires hourly ultrafiltration rates of 1e2 litres to help achieve urea clearance. The volume of ultrafiltrate produced is replaced, in part or completely, by infusing buffered replacement fluids. Reducing the volume returned to the patient results in net fluid removal. The replacement fluid generally consists of a balanced electrolyte solution, which is either bicarbonate or lactate based. These solutions are added into the circuit before the haemofilter termed pre-dilution, after the filter termed post-dilution, but is most commonly on both sides of the filter. Pre-dilution dilutes the blood that is filtered, so prolonging the circuit life span by decreasing the clotting risk. However, this is inefficient for urea clearance. Increasing post-dilution administration leads to a greater urea clearance.
Safe to use in renal failure. Concern has been raised regarding the use of sevoflurane, due to the decreased excretion of fluoride ions, which may accumulate and worsen renal failure. Further, its metabolite Compound A production has been shown to be nephrotoxic in rats, but no clinical effect is seen in humans
Haemodialysis HD is a process in which diffusion across a semipermeable membrane is used to remove solutes. The patient’s blood is pumped past one side of the membrane, while dialysate fluid of a differing concentration is infused on the other. The concentration gradient created allows waste molecules to diffuse from the plasma into the dialysate fluid. Counter-current flow of the blood and dialysate fluid across the membrane prevents the achievement of equilibrium, maintaining the concentration gradient for diffusion. HD can be continuous, but is mostly intermittent in the setting of ESRF or in the stable patient with AKI.
Table 3
large burden on the patient’s and family’s lifestyle, with regular attendance at hospital required for RRT. However there have been tremendous efforts to move RRT out of hospital and to facilitate patients and their families doing their PD, and more recently, HD at home. For patients on chronic RRT, renal transplantation offers improved survival, better quality of life and is cost-effective in health economic terms. It may be either a cadaveric transplant or increasingly a kidney donated from a living relative.
Haemodiafiltration Haemodiafiltration combines dialysis with the filtration process, to remove water and waste products. Through the process of making diffusion and convection occur simultaneously, the
Mimicking the kidney The kidneys normally remove excess water and waste products through filtration. RRT mimics this action through the use of
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Components and function of a veno-venous haemodiafiltration circuit Circuit pressure monitors
Dialysate infusion Dual lumen venous catheter
Air and clot trap Haemofilter
Air detector Clamp
Heparin infusion
Ultrafiltration collection bag
Roller pump Replacement fluid infusion Reproduced from Murphy T, Robinson S. Anaesthesia and Intensive Care Medicine 2006;7:247
Figure 2
efficiency and speed of waste (urea) clearance is increased. The fluid used for dialysis and fluid replacement is the same and so a large amount is required.
patient body habitus, clinical condition, coagulopathic status and the site of other lines. The use of ultrasound is recommended when placing any CVC to improve patient safety. The artificial membranes used in RRT circuits are biocompatible materials (cellulose, polysulfone or methylmethacrylate). Despite being biocompatible, on exposure of blood to the foreign material, platelets and the intrinsic and extrinsic clotting cascade are both activated. Thus, anticoagulation is required to prevent thrombus formation and malfunction of the circuit. Anticoagulation is not recommended in the presence of an increased bleeding risk or impaired coagulation. Anticoagulation may be achieved via one of three methods. The most commonly used anticoagulant is unfractionated heparin, aiming to maintain an activated partial thromboplastin time ratio 1.5e2.5 times normal. This is particularly useful in acute RRT scenarios. Complications include bleeding and heparin-induced thrombocytopenia. LMWHs, despite having a more consistent bioavailability and being less likely to promote heparin-induced thrombocytopenia, are rarely used. There is no reliable reversal agent and a non-routine test is needed to monitor action (anti-factor Xa). Prostacyclin (prostglandin I2) provides a useful alternative anticoagulant, through its inhibitory effect on platelet reactivity and aggregation. Adverse effects include vasodilation and reversal of hypoxic pulmonary vasoconstriction, potentially exacerbating hypoxaemia. Citrate is as an ideal anticoagulant providing regional anticoagulation of the extracorporeal circuit without the need for systemic anticoagulation. Citrate forms a complex with calcium, preventing its role in the generation of thrombin and secondary clotting. Citrate reaching the systemic circulation is metabolized by the liver, muscle and kidney. Calcium levels must be monitored in the patient during use (risk of hypocalcaemia), as the
Slow continuous ultrafiltration This is a haemofiltration technique used mainly for fluid removal in overloaded patients. No dialysate or replacement fluids are used and the ultrafiltrate that is generated corresponds to weight loss. The fluid removed is regulated to produce a slow continuous plasma water loss, normally when a patient has proven resistant to diuretics. Peritoneal dialysis Dialysis fluid is inserted into the peritoneal cavity via a surgically inserted catheter. The peritoneum then acts as a semipermeable membrane, between the blood in the capillaries and the fluid. Through the tonicity gradient created by the dialysate, fluid solute and water movement is achieved. After a period of equilibration, the dialysate fluid is removed. The process may be continuous or intermittent and is used mainly for home dialysis. Fluid removal is not as good as other forms of RRT and it tends to be used in the early stages of RRT. Access and anticoagulation Acute RRT through CRRT or HD will be via a dual lumen central venous catheter (CVC). Patients on long-term RRT for ESRF will usually have a surgically created arteriovenous fistula for HD, or a peritoneal catheter for PD. A number will continue on HD via a long-term CVC. Catheters are polyurethane, being stiff for insertion and avoiding collapse at high negative pressures. Longterm catheters may be tunnelled to reduce infection risk. Sites of CVC placement include the commonly used internal jugular or femoral veins. The subclavian vein may also be used. Decision on placement sites will involve the assessment of the
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2 NCEPOD. ‘Adding Insult to Injury’. A review of the care of patients who died in hospital with a primary diagnosis of acute kidney injury. 2009, http://www.ncepod.org.uk/2009report1/Downloads/AKI_report.pdf. 3 Challiner Rachael, Szeki Iren. Greater Manchester Renal Network and Greater Manchester Critical Care Network. Acute Kidney Injury Guidelines 2010. 4 Parikh CR, Devarajan P. New biomarkers of acute kidney injury. Crit Care Med 2008 Apr; 36(4 suppl): S159e65. 5 Villa P, Jimenez M, Soriano MC, et al. Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients. Crit Care 2005; 9: R139e43. 6 Kidney Disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 2013;(suppl 3); 1e150. 7 Gentz BA, Malan Jr TP. Renal toxicity with sevoflurane: a storm in a teacup? Drugs 2001; 61(15): 2155e62. 8 Standards and recommendations for the provision of RRT on ITUs in the UK Intensive Care Society Standards and Safety 2009.
circuit filters the citrate complex. Liver failure is a contraindication to use. It is expensive and requires adherence to a strict protocol, but the cost is offset by the improved life span of CVVF circuits and the possibility that it may improve survival. Further advantages include a reduced risk of bleeding in the patient. It is suggested as an option for patients undergoing CRRT. Lastly, although not an anticoagulant, alterations in the ratio of pre-dilution to post-dilution may also affect clotting within the circuit. Increasing pre-dilution flows reduces haematocrit levels, reducing the tendency for clot formation. However, this reduces the filtration fraction, reducing the efficiency of the circuit. Often a balance may be achieved depending on the individual circumstances of the patient. A REFERENCES 1 Mehta RL, Kellum JA, Shah SV, et al. Acute kidney injury network. Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31.
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