Preventing Renal Failure in the Critically Ill

Few doctors trained in the past 20 years have not learnt of the benefits of “low dose” dopamine in patients developing acute renal failure. The belief that low dose dopamine is beneficial was based on the physiological and pharmacological properties of dopamine and on personal anecdotes, but there is a lack of clinical trials, those available being of poor quality.1 The recent publication of a high quality randomised, double blind, placebo controlled study2 showing no benefit of “low dose” dopamine has, therefore, killedor at least mortally wounded given that it takes time for cardiac surgeons to catch upone of critical care’s sacred cows.

In this study 328 patients (in 23 Australasian intensive care units) with an acute inflammatory response and early renal dysfunction (raised serum creatinine concentration or oliguria) randomly received a dopamine infusion (2 µg/kg/min) or placebo. The primary outcome variable, peak serum creatinine concentration during infusion, did not differ between the well matched groups. Moreover, there was no difference in any other variable studied, including requirement for dialysis. Indeed, urine output and use of frusemide did not differ, suggesting that dopamine was not even an effective diuretic. A possible criticism of the study is that the patients had already established renal dysfunction at time of entry, and some proponents of dopamine would argue that it is only likely to be of benefit if used as prophylaxis. However, the failure of dopamine to influence any study endpoint makes even this suggestion unlikely.

The results are actually not surprising. The weight of evidence has long been against the use of dopamine, especially as its adverse effects (inappropriate vasoconstriction, tachyarrhythmias, reduced respiratory drive, increased intrapulmonary shunt, altered immune and endocrine responses, and reduced splanchnic perfusion) are well recognised.1 Low dose dopamine can no longer be considered to “do no harm and possibly do some good,” as we were taught, and this study conclusively shows that dopamine has no role in preventing acute renal failure in critical illness.

If dopamine is out then what is in? The development of acute renal failure in hospital significantly increases a patient’s risk of death (odds ratio for death 5.5 for contrast induced renal dysfunction3). When it occurs in intensive care in combination with acute respiratory failure, mortality exceeds 50% even in the best centres.4 Prevention is therefore vitally important. Acute renal failure is generally associated with renal hypoperfusion often in association with severe sepsis or relative or absolute hypovolaemia or as a consequence of pump failure. Thus its prevention requires meticulous attention to the systemic haemodynamic disturbance, fluid balance, and the avoidance of nephrotoxins.

Invasive haemodynamic monitoring and optimum fluid management have never been studied in a prospective clinical trial, however, other than in those that have focused on perioperative management of high risk surgical patients. In this population the weight of the evidence seems to favour intensive haemodynamic monitoring with aggressive fluid therapy as a means of reducing overall morbidity and mortality.5-7 In contrast, in the general intensive care unit population there is no evidence to support targeting any specific cardiac filling pressure or the use of any particular resuscitation fluid. Given the ready availability of mechanical ventilation and renal support (haemodialysis or filtration), we advocate generous fluid resuscitation in patients with oliguria and renal dysfunction. Access to the central venous pressure may help guide adequacy of resuscitation, but in patients with cardiac or respiratory disease measurement of pulmonary artery occlusion pressure may be more accurate. Both pressures can be influenced by factors other than blood volume, however, and interpretation of pressure traces is subject to considerable interobserver variability.8 Hence modern monitoring techniques reporting circulatory volumes and lung water may in time be shown to be more useful. Fluid overload resulting in impaired pulmonary gas exchange should be avoided whenever possible, but if it does occur initial treatment is with high dose diuretics. Failure to respond suggests established acute renal failure and requirement for dialysis.

Optimisation of “preload” with adequate fluid resuscitation may not be enough. In critical illness renal perfusion pressure and renal blood flow develop a linear relation.9 The vasopressor catecholamine norepinephrine has been shown in clinical studies of sepsis to increase renal blood flow and improve renal function.10 Again, a lower acceptable limit for mean arterial pressure compatible with adequate renal perfusion is not defined. For most patients a level of 70 mm Hg is probably adequate, higher levels being needed in elderly people or those with hypertension. A good rule is to aim for the premorbid mean arterial pressure or seek the lowest pressure that maintains adequate end organ function. In cardiogenic shock or after cardiac surgery augmentation of perfusion pressure by intra-aortic balloon counterpulsation is also associated with improved renal function.11 Raised intra-abdominal pressure is another factor that impairs renal perfusion despite normal or raised mean arterial pressure. Improvements in renal function often occur after decompressive laparotomy or drainage of tense ascites.12

What of pharmacological manipulations? Apart from avoiding nephrotoxins such as aminoglycosides and iodinated radiocontrast agents, there is little to recommend. Frusemide may induce diuresis and ease fluid management, but there is no evidence that promoting diuresis in acute renal failure improves outcome.13 Similarly, there is no evidence to support the use of mannitol, a nephrotoxin, in high doses. A few new agents remain under investigation, but there is not yet enough evidence to recommend them.14 In a small double blind, placebo controlled, randomised trial the free radical scavenger N-acetylcysteine attenuated the rise in serum creatinine concentration in patients with renal dysfunction receiving radiocontrast agents.15 In our view, prevention of renal dysfunction in critical illness is simply a case of “back to basics”: optimise volume and defend pressure.

Michael J O’Leary, staff specialist in intensive care.

St George Hospital, Kogarah, NSW 2217, Australia ([email protected])

David J Bihari, associate professor in intensive care.

Prince of Wales Hospital, Randwick, NSW 2023, Australia