Chronic Kidney Disease and Anaesthesia
Highlights
- 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 (Page 2)
- 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 (Page 2)
- 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. (Page 2)
- CKD can cause metabolic disturbances including hyperkalaemia, metabolic acidosis, hyperphosphataemia, hypocalcaemia, hypermagnesaemia, hyperuricaemia and hypoalbuminaemia (Page 2)
- 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 (Page 3)
- 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-Daspartate (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. (Page 4)
- Chronic kidney disease also represents a prothrombotic state caused by decreased fibrinolysis, increased initial fibrin formation, increased fibrineplatelet interaction and increased qualitative platelet function. (Page 4)
- 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. (Page 5)
- 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. (Page 5)
- Distribution The volume of distribution (VD) 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 (Page 5)
- the main binding site for basic drugs. Hydrophilic drugs exhibit an increase in VD (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. (Page 6)
- 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. (Page 6)
- 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. (Page 6)
- 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. (Page 7)
- Sugammadex has been used successfully in clinical research to reverse blockade from aminosteroid NMBAs in patients with severe renal impairment. The sugammadexe rocuronium complex can persist in vivo for up to 7 days. The rocuroniumesugammadex complex is very stable and can be cleared by high-flow dialysis. (Page 7)
- Tramadol is 30% excreted unchanged in the urine. It may be epileptogenic in the context of uraemia because of the lowered seizure threshold. (Page 7)
Chronic Kidney Disease and Anaesthesia
Highlights
- 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 (Page 2)
- 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 (Page 2)
- 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. (Page 2)
- CKD can cause metabolic disturbances including hyperkalaemia, metabolic acidosis, hyperphosphataemia, hypocalcaemia, hypermagnesaemia, hyperuricaemia and hypoalbuminaemia (Page 2)
- 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 (Page 3)
- 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-Daspartate (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. (Page 4)
- Chronic kidney disease also represents a prothrombotic state caused by decreased fibrinolysis, increased initial fibrin formation, increased fibrineplatelet interaction and increased qualitative platelet function. (Page 4)
- 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. (Page 5)
- 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. (Page 5)
- Distribution The volume of distribution (VD) 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 (Page 5)
- the main binding site for basic drugs. Hydrophilic drugs exhibit an increase in VD (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. (Page 6)
- 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. (Page 6)
- 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. (Page 6)
- 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. (Page 7)
- Sugammadex has been used successfully in clinical research to reverse blockade from aminosteroid NMBAs in patients with severe renal impairment. The sugammadexe rocuronium complex can persist in vivo for up to 7 days. The rocuroniumesugammadex complex is very stable and can be cleared by high-flow dialysis. (Page 7)
- Tramadol is 30% excreted unchanged in the urine. It may be epileptogenic in the context of uraemia because of the lowered seizure threshold. (Page 7)