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The management of acute renal failure in the intensive care unit
The Management of Acute Renal Failure in the Intensive Care Unit
R. Beale and D. Bihari
Introduction
and waste clearance is inadequate to prevent a deterioration in biochemistry. ARF occurring 'de novo' without a background of pre-existing renal impairment normally recovers assuming that the patient survives the causative illness. Having ascertained that renal dysfunction is developing, it is important to identify the cause, and to treat it if possible, ideally before that stage at which ARF becomes established and renal replacement becomes necessary. There is usually a history of an event or sequence of events which might be expected to cause renal failure. In the ICU the most common precipitating factors are infection, hypotension and hypoxia. In these circumstances the development of ARF may be insidious as patients suffering from MOF are likely to suffer multiple insults. Alternatively, there may be a clear event which caused the renal failure, such as a single episode of prolonged and profound hypotension. A less dramatic event may be equally damaging, however, if there is already an element of chronic renal impairment, as is likely to be the case in patients with hypertension or diabetes. There are also often iatrogenic components to the ARF of critical illness, which will be apparent from the history. Commonplace amongst these are inadequate and delayed resuscitation; deterioration during inadequately monitored and supervised transfer; aminoglycoside toxicity due to insufficiently frequent monitoring of levels; and NSAID toxicity due to the lack of appreciation of the devastating effects of blocking protaglandin metabolism under circumstances where renal blood flow is impaired (e.g. trauma with shock). It should also be remembered that some specific disease entities, particularly vasculitis, can cause renal and respiratory failure and are amenable to specific treatment. Although rare, these
The mortality of acute renal failure (ARF) occurring in the intensive care unit (ICU) is high. Such patients usually have ARF as part of the syndrome of multiple organ failure (MOF), since ARF alone is usually treated in renal units. In a single large UK centre the survival of patients with renal and respiratory failure (i.e. patients needing both renal and ventilatory support) between 1970-1979 was 33%; and between 1980-1988 the survival was 38%.a These figures are typical of those of many series published in the last 10 years, and illustrate the severity of the problem. It is important to stress that very few such patients actually die of their renal failure. ARF within the ICU is usually a consequence of, or part of, a systemic disease process. In this context the kidney is a target of end-organ damage but, since its function can usually be supported adequately, patient outcome is dependent upon recovery from the underlying illness.
Diagnosis The recognition that renal impairment, and ultimately established failure, has occurred is not usually difficult. There is a rise in serum urea and creatinine, and there may be an associated rise in serum potassium. Typically a metabolic acidosis develops. Urine output usually diminishes and may often cease, at which point established ARF has developed, and renal support will be required for several days even if the underlying insult is reversed. Occasionally the patient continues to pass urine, but the quality is poor Richard Beale FC Anaes, David Bihari MRCP, Intensive Care Unit, G u y ' s Hospital, St T h o m a s Street London SE1 9RT, U K Current Anaesthesia and Critical Care
© 1992LongmanGroup UK Ltd
(1992) 3, 146-149 146
T H E M A N A G E M E N T OF A C U T E R E N A L F A I L U R E IN T H E I N T E N S I V E C A R E U N I T
are more likely in patients where no clear precipitating factor can be found to explain the onset of ARF, and specialist advice is necessary for their therapy. It is conventional to categorise ARF into 'prerenal', 'renal' and 'post-renal'. These distinctions are of limited value in the ICU since the ARF of MOF is often multi-factorial, and elements of all three mechanisms may co-exist. Nevertheless, they serve to focus attention on various key features. 'Pre-renal' refers particularly to the adequacy of renal perfusion, as determined by the degree of hydration, and the state of the cardiovascular system in terms of cardiac filling and performance. Clinical examination and invasive cardiovascular monitoring are the most important tools for assessing these, and the large majority of patients with MOF with renal failure will require pulmonary artery catheterization. It is sometimes suggested that the measurement of urinary electrolytes is helpful in detecting 'pre-renal' renal failure. In circumstances of hypoperfusion the kidney concentrates urine in an attempt to conserve salt and water and the urinary sodium concentration may fall to below 20mmol/1. Subsequently, as renal failure becomes established and tubular function is lost, the urinary sodium concentration rises to above 30mmol/l and may approach serum levels. Often, however, the urinary sodium values are difficult to interpret. Diuretics will nearly always have been used, and the values may be low anyway in the hepato-renal syndrome, burns and sepsis. The difference between blood and urinary area concentrations may be more useful (urinary urea > 20x blood urea with normal renal function), and is helpful in assessing decline and recovery in renal function and the timing of renal support. 'Renal' refers to those processes damaging the kidney directly. Nephrotoxic drugs may be classified under this heading but, in the context of the ICU patient with ARF and MOF, the kidney is a target for the cytokine-mediated inflammatory process which may affect every organ system. The precise details of these events, and the mechanisms responsible for the development of ARF, are yet to be elucidated. At a macroscopic level it is important to ascertain the presence of two kidneys, and their sizes, which may indicate the presence of chronic renal impairment. This is most readily done by bedside ultrasound examination, which will also detect dilatation of the collecting systems. Doppler ultrasound may provide valuable information about the renal blood supply. 'Post-renal' refers to obstruction of the outflow of urine. This may occur anywhere between the renal pelvis and the urethra, but must be bilateral to cause renal failure in the presence of two previously functioning normal kidneys. It may be detected by ultrasound scan. In the ICU the most common cause of urinary tract obstruction is bladder catheter blockage, and this should always be suspected in the presence of complete anuria.
147
Another important cause of urinary tract obstruction in the ICU is raised intra-abdominal pressure (IAP). This occurs most commonly as a result of intra-abdominal bleeding, often the continuing slow oozing of blood after major abdominal surgery or abdominal trauma, particularly in the presence of a coagulopathy. It may also result from intestinal distension and ascites. In dogs increasing the IAP from 0mmHg was associated with a 25% decrease in glomerular filtration rate, whilst anuria developed when the lAP reached 40mmHg. 2 The exact mechanism by which raised IAP causes a reduction in urine output is unclear. It is likely that venous return and cardiac output are reduced, particularly in the presence of hypovolaemia, and that therefore renal blood flow (RBF) is impaired. Another possible mechanism is that renal vein compression occurs, with reflex renal artery vasoconstriction and a reduction in RBF and urine output. Direct ureteric compression is less likely a cause since the renal collecting system is able to generate pressures of up to 90mmHg. Another hypothesis is that in the patient with raised IAP the proximal renal tubular pressure (PRTP) approximates the lAP. The filtration gradient (FG) across the glomerular capillary membrane is the difference between the glomerular pressure (GP) and the PRTP. An estimate of the glomerular filtration pressure is given by the difference between the mean arterial pressure (MAP) and the IAP. 3 i.e. and so
e.g.
FG = G P - P R T P = G P - I A P GP = M A P - I A P FG = MAP - 2 (IAP) if MAP = 80 mmHg and IAP = 40 mmHg then FG -- 0
IAP may readily be measured either by placing a catheter into the inferior vena cava (IVC), since IVC pressure and IAP approximate very closely, or by measuring the intravesical pressure which is also a close approximation. This second technique relies on the property of the bladder of being freely distensible at small volumes. 100ml of sterile saline is instilled through the catheter which is then clamped proximal to the sampling port on the catheter tubing. A needle attached to a pressure transducer levelled with the pubic symphysis is inserted through the sampling port diaphragm and the pressure recorded. Anuria and an IAP of 30-40 mmHg associated with intra-abdominal bleeding may be an indication for laparotomy. Two causes of ARF deserve mention. Rhabdomyolysis may occur after crush injuries or due to muscle ischaemia and compartment syndrome. Reperfusion of damaged muscle liberates cellular contents into the circulation, including potassium, phosphates and myoglobin. Myoglobinuria may result and, if hypovolaemia and oliguria are present, renal failure ensues, due in part to the specific tubular toxicity of myoglobin. The syndrome was first recognised during the London Blitz in the Second World
148
CURRENTANAESTHESIA AND CRITICALCARE
War, and it was subsequently appreciated that maintaining a high urine output and alkalinising the urine could prevent ARF developing. 4 Hepato-renal syndrome is a specific type of ARF seen in patients with fulminant liver failure, in which the kidneys produce only small amounts of very concentrated urine (urinary sodium < lOmmol/1). Oliguria persists even when renal perfusion is maintained, and does not respond to diuretics. If the patient undergoes liver transplantation, normal renal function is restored. If a kidney from such a patient is transplanted into a patient with a normal liver, it will function normally. A variety of inflammatory mediators have been implicated in this process, and currently much interest is directed at the role of leukotrienes in the aetiology of hepato-renal syndrome. 5 Treatment The treatment of ARF in the ICU can be divided into manoeuvres which are intended to prevent renal failure developing or to reverse it before it becomes established, and manoeuvres designed to replace function until such time as recovery occurs. Paramount within the frst category is treatment of the underlying cause of the ARF. Infection should be treated, hypotension corrected, bleeding controlled and nephrotoxic drugs avoided or stopped. Since ARF in the ICU is so often multi-factorial, in essence the treatment is really no more than the provision of meticulous intensive care. The achievement of optimum cardiovascular performance may be crucial to maintaining renal perfusion, and is difficult without the use of a pulmonary artery catheter to allow appropriate volume loading and to guide the use of inotropes. Unfortunately, it is not always clear what the targets of such 'optimization' should be. The fashion for attempting to achieve specific values of global oxygen delivery and uptake, with the emphasis on blood flow rather than pressure, may not always place sufficient emphasis on ensuring an adequate renal perfusion pressure. Equally, the approach reliant upon vasoconstrictors to maintain blood pressure is often thought to jeopardize the kidneys since adrenaline and noradrenaline are renal vasoconstrictors in health. The situation is further muddied by the observation in animal studies that renal blood flow in ARF becomes entirely pressure dependent since autoregulation is lost. 6 It is certainly true that deliberately raising the blood pressure with noradrenaline in a patient with developing renal failure (presuming that the general condition of the patient does not prevent this manoeuvre) may sometimes maintain urine output, although its quality may be poor. Since the management of the patient with ARF is facilitated if some urine output can be preserved, and the survival rate for polyuric ARF may be better than that for oliguric ARF, attempts are usually made to stimulate urine output. Apart from the general
principles outlined above, specific therapies include the use of low-dose dopamine, diuretics (usually frusemide) and mannitol. Low-dose dopamine infusion (1-3mcg/kg/min) is administered in an attempt to obtain a specific dopaminergic renal vasodilating action without the inotropic effects achieved at higher doses. Although renal blood flow and urine output are increased in the healthy kidney, there is no clear evidence that 'renal-dose' dopamine is able to prevent or to reverse developing ARF. Nevertheless, it is used very widely. The newer agent dopexamine combines specific dopaminergic and beta-2 effects, and may have actions on the kidney similar to those of dopamine. Frusemide may be useful in attempting to stimulate urine output, and many different strategies are used. Of course, diuretics cannot be effective if renal perfusion is inadequate. One approach is to infuse frusemide at a rate of 4 mg/min up to a maximum dose of 1 gm, once more conventional doses have failed. If there is no response to a dose of this size, the necessity for renal support is virtually inevitable. The osmotic diuretic mannitol is sometimes employed to try and restore urine output. Again, adequate renal perfusion is necessary for any effect. There is also a risk of circulatory overload if large doses are given unsuccessfully. Once ARF becomes established, the aim of therapy is to provide artificial renal support until recovery eventually occurs. There are three main types of renal replacement used in the ICU: peritoneal dialysis (PD), intermittent haemodialysis (IHD) and continuous haemofiltration/haemodiafiltration (CAVH/CAVHD/CVVH/CVVHD). PD entails running dialysis fluid into and out of the peritoneal cavity via a plastic catheter. Fluids are glucose based, and the tonicity can be varied in order to facilitate fluid removal. Complications include infection and diaphragmatic splinting; recent abdominal surgery is usually a contraindication. The capacity of the technique to achieve biochemical control and adequate fluid removal is limited, and it is rarely used now. IHD is the traditional mode of renal replacement, and requires the use of a conventional haemodialysis machine. It is usually only available where there is a renal unit. Since treatments are intermittent, control of biochemistry and fluid balance is necessarily episodic. There is a propensity for haemodynamic instability. IHD is being superseded by the continuous techniques. Continuous haemofiltration entails the passage of blood across a highly-permeable synthetic membrane. Water and solutes are driven across the membrane by the hydrostatic pressure in the blood compartment, and replaced with an ideal electrolyte solution. Clearance may be increased by passing replacement fluid through the filtrate compartment of the membrane, where it acts as dialysis fluid. This is then haemodiafiltration. The patient's own blood
THE M A N A G E M E N T OF ACUTE RENAL FAILURE IN THE INTENSIVE CARE UNIT
pressure may be used to drive blood continuously through an arterio-venous system (continuous arterio-venous haemofiltration-CAVH/continuous arterio-venous haemodiafiltration-CAVHD), or a double-lumen dialysis catheter and a blood pump employed (continuous veno-venous haemofiltrationCVVH/continuous veno-venous haemodiafiltrationCVVHD). Biochemical control (except possibly with CAVH) and fluid balance are usually satisfactorily controlled, but continuous anti-coagulation is required. Modes of renal replacement are discussed in more detail elsewhere in this issue.
Conclusion Although none of the available methods of renal support in the ICU is ideal, it is usually possible to prevent patients dying as a direct consequence of their renal failure. That the survival of patients with ARF in the ICU has not really improved in the last 20 years probably reflects the lack of progress that has been made in treating the underlying condition: multiple organ failure. It may be that the new
149
developments in immunotherapy, with monoclonal antibodies being directed at various mediators in the inflammatory cascade, herald a real advance, although more evidence is needed. Until such time as the survival for MOF improves, however, the prognosis of patients with ARF in the ICU will remain gloomy.
References 1. Turney JH, Marshall DH, Brownjohn AM, Ellis CM, Parsons FM. The Evolution of Acute Renal Failure. Q J Med 1990; 74:83-104 2. Harman PK, Kron IL, McLaehlan HD. Elevated Intraabdominal Pressure and Renal Function. Ann Surg 1982; 196:594-597 3 Caldwell CB, Ricotta JJ. Changes in Visceral Blood Flow with Elevated Intra-abdominal Pressure. J Surg Res 1987; 43: 14-20 4. Bywaters EGL, Beall D. Crush Injuries with Impairment of Renal Function. Br J Med 1941; i: 427-432 5. Moore KP, Taylor CW, Maltby NH, Siegers D, Fuller RW, Dollery CT, Williams R. Increased Production of Cysteinyl Leukotrienes in Hepatorenal Syndrome. J Hepatol 1990; 11 (2): 263-271 6. KeUeher SP, Robinette JB, Conger JD. Sympathetic Nervous System in the Loss of Autoregulation in Acute Renal Failure. Am J Physiol 1984; 246:379-386
R. Beale and D. Bihari
Introduction
and waste clearance is inadequate to prevent a deterioration in biochemistry. ARF occurring 'de novo' without a background of pre-existing renal impairment normally recovers assuming that the patient survives the causative illness. Having ascertained that renal dysfunction is developing, it is important to identify the cause, and to treat it if possible, ideally before that stage at which ARF becomes established and renal replacement becomes necessary. There is usually a history of an event or sequence of events which might be expected to cause renal failure. In the ICU the most common precipitating factors are infection, hypotension and hypoxia. In these circumstances the development of ARF may be insidious as patients suffering from MOF are likely to suffer multiple insults. Alternatively, there may be a clear event which caused the renal failure, such as a single episode of prolonged and profound hypotension. A less dramatic event may be equally damaging, however, if there is already an element of chronic renal impairment, as is likely to be the case in patients with hypertension or diabetes. There are also often iatrogenic components to the ARF of critical illness, which will be apparent from the history. Commonplace amongst these are inadequate and delayed resuscitation; deterioration during inadequately monitored and supervised transfer; aminoglycoside toxicity due to insufficiently frequent monitoring of levels; and NSAID toxicity due to the lack of appreciation of the devastating effects of blocking protaglandin metabolism under circumstances where renal blood flow is impaired (e.g. trauma with shock). It should also be remembered that some specific disease entities, particularly vasculitis, can cause renal and respiratory failure and are amenable to specific treatment. Although rare, these
The mortality of acute renal failure (ARF) occurring in the intensive care unit (ICU) is high. Such patients usually have ARF as part of the syndrome of multiple organ failure (MOF), since ARF alone is usually treated in renal units. In a single large UK centre the survival of patients with renal and respiratory failure (i.e. patients needing both renal and ventilatory support) between 1970-1979 was 33%; and between 1980-1988 the survival was 38%.a These figures are typical of those of many series published in the last 10 years, and illustrate the severity of the problem. It is important to stress that very few such patients actually die of their renal failure. ARF within the ICU is usually a consequence of, or part of, a systemic disease process. In this context the kidney is a target of end-organ damage but, since its function can usually be supported adequately, patient outcome is dependent upon recovery from the underlying illness.
Diagnosis The recognition that renal impairment, and ultimately established failure, has occurred is not usually difficult. There is a rise in serum urea and creatinine, and there may be an associated rise in serum potassium. Typically a metabolic acidosis develops. Urine output usually diminishes and may often cease, at which point established ARF has developed, and renal support will be required for several days even if the underlying insult is reversed. Occasionally the patient continues to pass urine, but the quality is poor Richard Beale FC Anaes, David Bihari MRCP, Intensive Care Unit, G u y ' s Hospital, St T h o m a s Street London SE1 9RT, U K Current Anaesthesia and Critical Care
© 1992LongmanGroup UK Ltd
(1992) 3, 146-149 146
T H E M A N A G E M E N T OF A C U T E R E N A L F A I L U R E IN T H E I N T E N S I V E C A R E U N I T
are more likely in patients where no clear precipitating factor can be found to explain the onset of ARF, and specialist advice is necessary for their therapy. It is conventional to categorise ARF into 'prerenal', 'renal' and 'post-renal'. These distinctions are of limited value in the ICU since the ARF of MOF is often multi-factorial, and elements of all three mechanisms may co-exist. Nevertheless, they serve to focus attention on various key features. 'Pre-renal' refers particularly to the adequacy of renal perfusion, as determined by the degree of hydration, and the state of the cardiovascular system in terms of cardiac filling and performance. Clinical examination and invasive cardiovascular monitoring are the most important tools for assessing these, and the large majority of patients with MOF with renal failure will require pulmonary artery catheterization. It is sometimes suggested that the measurement of urinary electrolytes is helpful in detecting 'pre-renal' renal failure. In circumstances of hypoperfusion the kidney concentrates urine in an attempt to conserve salt and water and the urinary sodium concentration may fall to below 20mmol/1. Subsequently, as renal failure becomes established and tubular function is lost, the urinary sodium concentration rises to above 30mmol/l and may approach serum levels. Often, however, the urinary sodium values are difficult to interpret. Diuretics will nearly always have been used, and the values may be low anyway in the hepato-renal syndrome, burns and sepsis. The difference between blood and urinary area concentrations may be more useful (urinary urea > 20x blood urea with normal renal function), and is helpful in assessing decline and recovery in renal function and the timing of renal support. 'Renal' refers to those processes damaging the kidney directly. Nephrotoxic drugs may be classified under this heading but, in the context of the ICU patient with ARF and MOF, the kidney is a target for the cytokine-mediated inflammatory process which may affect every organ system. The precise details of these events, and the mechanisms responsible for the development of ARF, are yet to be elucidated. At a macroscopic level it is important to ascertain the presence of two kidneys, and their sizes, which may indicate the presence of chronic renal impairment. This is most readily done by bedside ultrasound examination, which will also detect dilatation of the collecting systems. Doppler ultrasound may provide valuable information about the renal blood supply. 'Post-renal' refers to obstruction of the outflow of urine. This may occur anywhere between the renal pelvis and the urethra, but must be bilateral to cause renal failure in the presence of two previously functioning normal kidneys. It may be detected by ultrasound scan. In the ICU the most common cause of urinary tract obstruction is bladder catheter blockage, and this should always be suspected in the presence of complete anuria.
147
Another important cause of urinary tract obstruction in the ICU is raised intra-abdominal pressure (IAP). This occurs most commonly as a result of intra-abdominal bleeding, often the continuing slow oozing of blood after major abdominal surgery or abdominal trauma, particularly in the presence of a coagulopathy. It may also result from intestinal distension and ascites. In dogs increasing the IAP from 0mmHg was associated with a 25% decrease in glomerular filtration rate, whilst anuria developed when the lAP reached 40mmHg. 2 The exact mechanism by which raised IAP causes a reduction in urine output is unclear. It is likely that venous return and cardiac output are reduced, particularly in the presence of hypovolaemia, and that therefore renal blood flow (RBF) is impaired. Another possible mechanism is that renal vein compression occurs, with reflex renal artery vasoconstriction and a reduction in RBF and urine output. Direct ureteric compression is less likely a cause since the renal collecting system is able to generate pressures of up to 90mmHg. Another hypothesis is that in the patient with raised IAP the proximal renal tubular pressure (PRTP) approximates the lAP. The filtration gradient (FG) across the glomerular capillary membrane is the difference between the glomerular pressure (GP) and the PRTP. An estimate of the glomerular filtration pressure is given by the difference between the mean arterial pressure (MAP) and the IAP. 3 i.e. and so
e.g.
FG = G P - P R T P = G P - I A P GP = M A P - I A P FG = MAP - 2 (IAP) if MAP = 80 mmHg and IAP = 40 mmHg then FG -- 0
IAP may readily be measured either by placing a catheter into the inferior vena cava (IVC), since IVC pressure and IAP approximate very closely, or by measuring the intravesical pressure which is also a close approximation. This second technique relies on the property of the bladder of being freely distensible at small volumes. 100ml of sterile saline is instilled through the catheter which is then clamped proximal to the sampling port on the catheter tubing. A needle attached to a pressure transducer levelled with the pubic symphysis is inserted through the sampling port diaphragm and the pressure recorded. Anuria and an IAP of 30-40 mmHg associated with intra-abdominal bleeding may be an indication for laparotomy. Two causes of ARF deserve mention. Rhabdomyolysis may occur after crush injuries or due to muscle ischaemia and compartment syndrome. Reperfusion of damaged muscle liberates cellular contents into the circulation, including potassium, phosphates and myoglobin. Myoglobinuria may result and, if hypovolaemia and oliguria are present, renal failure ensues, due in part to the specific tubular toxicity of myoglobin. The syndrome was first recognised during the London Blitz in the Second World
148
CURRENTANAESTHESIA AND CRITICALCARE
War, and it was subsequently appreciated that maintaining a high urine output and alkalinising the urine could prevent ARF developing. 4 Hepato-renal syndrome is a specific type of ARF seen in patients with fulminant liver failure, in which the kidneys produce only small amounts of very concentrated urine (urinary sodium < lOmmol/1). Oliguria persists even when renal perfusion is maintained, and does not respond to diuretics. If the patient undergoes liver transplantation, normal renal function is restored. If a kidney from such a patient is transplanted into a patient with a normal liver, it will function normally. A variety of inflammatory mediators have been implicated in this process, and currently much interest is directed at the role of leukotrienes in the aetiology of hepato-renal syndrome. 5 Treatment The treatment of ARF in the ICU can be divided into manoeuvres which are intended to prevent renal failure developing or to reverse it before it becomes established, and manoeuvres designed to replace function until such time as recovery occurs. Paramount within the frst category is treatment of the underlying cause of the ARF. Infection should be treated, hypotension corrected, bleeding controlled and nephrotoxic drugs avoided or stopped. Since ARF in the ICU is so often multi-factorial, in essence the treatment is really no more than the provision of meticulous intensive care. The achievement of optimum cardiovascular performance may be crucial to maintaining renal perfusion, and is difficult without the use of a pulmonary artery catheter to allow appropriate volume loading and to guide the use of inotropes. Unfortunately, it is not always clear what the targets of such 'optimization' should be. The fashion for attempting to achieve specific values of global oxygen delivery and uptake, with the emphasis on blood flow rather than pressure, may not always place sufficient emphasis on ensuring an adequate renal perfusion pressure. Equally, the approach reliant upon vasoconstrictors to maintain blood pressure is often thought to jeopardize the kidneys since adrenaline and noradrenaline are renal vasoconstrictors in health. The situation is further muddied by the observation in animal studies that renal blood flow in ARF becomes entirely pressure dependent since autoregulation is lost. 6 It is certainly true that deliberately raising the blood pressure with noradrenaline in a patient with developing renal failure (presuming that the general condition of the patient does not prevent this manoeuvre) may sometimes maintain urine output, although its quality may be poor. Since the management of the patient with ARF is facilitated if some urine output can be preserved, and the survival rate for polyuric ARF may be better than that for oliguric ARF, attempts are usually made to stimulate urine output. Apart from the general
principles outlined above, specific therapies include the use of low-dose dopamine, diuretics (usually frusemide) and mannitol. Low-dose dopamine infusion (1-3mcg/kg/min) is administered in an attempt to obtain a specific dopaminergic renal vasodilating action without the inotropic effects achieved at higher doses. Although renal blood flow and urine output are increased in the healthy kidney, there is no clear evidence that 'renal-dose' dopamine is able to prevent or to reverse developing ARF. Nevertheless, it is used very widely. The newer agent dopexamine combines specific dopaminergic and beta-2 effects, and may have actions on the kidney similar to those of dopamine. Frusemide may be useful in attempting to stimulate urine output, and many different strategies are used. Of course, diuretics cannot be effective if renal perfusion is inadequate. One approach is to infuse frusemide at a rate of 4 mg/min up to a maximum dose of 1 gm, once more conventional doses have failed. If there is no response to a dose of this size, the necessity for renal support is virtually inevitable. The osmotic diuretic mannitol is sometimes employed to try and restore urine output. Again, adequate renal perfusion is necessary for any effect. There is also a risk of circulatory overload if large doses are given unsuccessfully. Once ARF becomes established, the aim of therapy is to provide artificial renal support until recovery eventually occurs. There are three main types of renal replacement used in the ICU: peritoneal dialysis (PD), intermittent haemodialysis (IHD) and continuous haemofiltration/haemodiafiltration (CAVH/CAVHD/CVVH/CVVHD). PD entails running dialysis fluid into and out of the peritoneal cavity via a plastic catheter. Fluids are glucose based, and the tonicity can be varied in order to facilitate fluid removal. Complications include infection and diaphragmatic splinting; recent abdominal surgery is usually a contraindication. The capacity of the technique to achieve biochemical control and adequate fluid removal is limited, and it is rarely used now. IHD is the traditional mode of renal replacement, and requires the use of a conventional haemodialysis machine. It is usually only available where there is a renal unit. Since treatments are intermittent, control of biochemistry and fluid balance is necessarily episodic. There is a propensity for haemodynamic instability. IHD is being superseded by the continuous techniques. Continuous haemofiltration entails the passage of blood across a highly-permeable synthetic membrane. Water and solutes are driven across the membrane by the hydrostatic pressure in the blood compartment, and replaced with an ideal electrolyte solution. Clearance may be increased by passing replacement fluid through the filtrate compartment of the membrane, where it acts as dialysis fluid. This is then haemodiafiltration. The patient's own blood
THE M A N A G E M E N T OF ACUTE RENAL FAILURE IN THE INTENSIVE CARE UNIT
pressure may be used to drive blood continuously through an arterio-venous system (continuous arterio-venous haemofiltration-CAVH/continuous arterio-venous haemodiafiltration-CAVHD), or a double-lumen dialysis catheter and a blood pump employed (continuous veno-venous haemofiltrationCVVH/continuous veno-venous haemodiafiltrationCVVHD). Biochemical control (except possibly with CAVH) and fluid balance are usually satisfactorily controlled, but continuous anti-coagulation is required. Modes of renal replacement are discussed in more detail elsewhere in this issue.
Conclusion Although none of the available methods of renal support in the ICU is ideal, it is usually possible to prevent patients dying as a direct consequence of their renal failure. That the survival of patients with ARF in the ICU has not really improved in the last 20 years probably reflects the lack of progress that has been made in treating the underlying condition: multiple organ failure. It may be that the new
149
developments in immunotherapy, with monoclonal antibodies being directed at various mediators in the inflammatory cascade, herald a real advance, although more evidence is needed. Until such time as the survival for MOF improves, however, the prognosis of patients with ARF in the ICU will remain gloomy.
References 1. Turney JH, Marshall DH, Brownjohn AM, Ellis CM, Parsons FM. The Evolution of Acute Renal Failure. Q J Med 1990; 74:83-104 2. Harman PK, Kron IL, McLaehlan HD. Elevated Intraabdominal Pressure and Renal Function. Ann Surg 1982; 196:594-597 3 Caldwell CB, Ricotta JJ. Changes in Visceral Blood Flow with Elevated Intra-abdominal Pressure. J Surg Res 1987; 43: 14-20 4. Bywaters EGL, Beall D. Crush Injuries with Impairment of Renal Function. Br J Med 1941; i: 427-432 5. Moore KP, Taylor CW, Maltby NH, Siegers D, Fuller RW, Dollery CT, Williams R. Increased Production of Cysteinyl Leukotrienes in Hepatorenal Syndrome. J Hepatol 1990; 11 (2): 263-271 6. KeUeher SP, Robinette JB, Conger JD. Sympathetic Nervous System in the Loss of Autoregulation in Acute Renal Failure. Am J Physiol 1984; 246:379-386