The use of loop diuretics in acute renal failure in critically ill patients to reduce mortality, maintain renal function, or avoid the requirements for renal support

The use of loop diuretics in acute renal failure in critically ill patients to reduce mortality, maintain renal function, or avoid the requirements for renal support

Report by Anthony Davis, SpR in Anaesthesia

Checked by Ingrid Gooch, SpR in Anaesthesia

North West School of Anaesthesia, Manchester, UK

Abstract

A short cut review was carried out to establish whether loop diuretics are useful for critically ill patients with renal failure. A total of 1017 citations were reviewed of which two answered the three part question. The clinical bottom line is that in critically ill patients with acute renal failure, there is no evidence to suggest that the use of loop diuretics reduces mortality, reduces length of ITU/hospital stay, or increases the recovery of renal function.

Three part question

In [critically ill patients with acute renal failure] does [the use of loop diuretics] [reduce mortality, improve renal function, reduce length of ITU/hospital stay, or reduce requirements for renal replacement therapy]?

Clinical scenario

A 65 year old male presents to the emergency department with severe pneumonia. He is intubated and placed on a ventilator because of worsening hypoxia. He has no history of previous renal disease but becomes increasingly oliguric over the next 2 h despite adequate fluid resuscitation and vasopressor support. You wonder whether the administration of a loop diuretic in order to improve/maintain his urine output would improve his prognosis and reduce the need for continuous veno‐venous haemofiltration (CVVH).

Search strategy

Cochrane Database, Edition 2, 2006: Loop diuretics. OVID Medline 1966 to February week 1 2006, and EMBASE 1980 to February 2006: (exp Uraemia OR azotemia.mp OR exp Kidney Failure/ OR exp kidney failure, acute/ OR exp kidney tubular failure, acute/ OR acute tubular necrosis.mp OR acute renal failure.mp OR renal failure.mp OR acute kidney failure.mp OR ARF.mp) AND (exp Diuretics/ OR Diuretics.mp, OR loop diuretic$.mp OR exp furosemide/ OR frusemide.mp OR exp bumetanide/ OR bumetanide.mp OR burinex.mp OR lasix.mp OR torasemide.mp OR Torem.mp) and ((critically ill or critical illness).mp OR exp Critical Illness/ OR critical care.mp OR exp Critical Care/ OR intensive care.mp OR intensive care units.mp OR exp intensive care/) limited to English and humans.

Search outcome

A total of 97 papers were found on Medline and 721 papers on EMBASE of which only two directly answered the three part question (table 2). There were 209 citations in Cochrane. No new papers were found.

Table 2.

Author, date, country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study weaknesses
Uchino et al,	1743 patients in intensive	Prospective multi‐	Unadjusted hospital	Diuretic group (62.4%) v	Observational cohort
2004,	care units on renal	centre (54 centres),	mortality rates	controls (57.1%).	Heterogeneity of care
Australia	replacement therapy or with	multinational (23	Adjustments using	Odds ratio mortality	across 23 countries
(multicentre	acute renal failure (using	countries) cohort	three multivariant	1.25 (p<0.03)	Analytical methods can
study in 23)	pre‐defined criteria).	study. Three distinct	models	Overall odds ratio	only adjust for observed
countries	70% of patients were	multivariate		mortality similar for all	confounding variables
	treated with diuretics at	analyses were		three methods. Odds	not unobserved ones
	study inclusion. Frusemide	performed		ratio 1.21–1.22
	was the most commonly	using propensity		(CIs 0.92 to 1.6),
	used diuretic (98%)	scoring		p = 0.10 to p = 0.153
Mehta et al,	552 critically ill patients	Prospective	Relationship bet‐	Increased risk of death	Prospective observational
2002, USA	with acute renal	cohort study	ween diuretic use	and non‐recovery of	cohort study
	failure in four	October 1989	and mortality and	renal function with	Patients given diuretics were
	ITUs in California.	to 1995	non‐recovery of	diuretic use.	likely to be older and more
	326 patients (59%)		renal function	Odds ratio 1.77 (CIs	likely to have a history
	were treated with		Odds ratio of death	1.14 to 2.76) in group	of CCF (p<0.001) and had
	diuretics		when patients who	given diuretics	lower measured cardiac
			died in week 1	Odds ratio of death 3.12	index (p<0.001)
			were excluded	(CIs 1.73 to 5.62)	Some inclusion criteria
			Overall in‐hospital	Odds ratio 1.68	debatable
			mortality	(CIs 1.06 to 2.64)

Comment(s)

About one fifth of the cardiac output is directed to the kidneys. This exceeds the oxygen supply to other vital organs, such as the brain, heart, or liver. A very low fraction of oxygen delivered is extracted by the kidney, suggesting ample oxygen reserve. Paradoxically, the kidney is the organ which is most sensitive to hypoperfusion and hypoxia, with acute renal failure being one of the most frequent complications of hypotension. This is because of the physiological gradient of intrarenal oxygenation, which means that under normal physiological conditions the renal medulla functions at very low oxygen tensions. Many therapeutic interventions in the prevention or management of patients with acute renal failure have been investigated in clinical studies. Interventions to enhance renal blood flow and decrease tubular reabsorption seem to be a logical approach for the prevention of outer medullary hypoxic injury. Loop diuretics block the active sodium‐potassium‐chloride co‐transport in the apical membrane of the thick ascending limb renal tubular cells. The loop diuretic frusemide has been shown to reduce medullary demand by inhibiting solute reabsorption and to attenuate the severity of acute renal injury in animal models. It is postulated that it may protect the human kidney from ischaemic injury. There are some small studies of low statistical power, but they are confounded by co‐interventions such as low dose dopamine or mannitol. The best evidence to answer this current clinical question comes from the two observational cohorts identified in this review. The two studies collected over 2000 patients. They both document overall detriment with the use of diuretics with odds ratios of >1.0, as opposed to benefit, although the BEST investigators did not demonstrate statistical significance in their findings. The question of whether an RCT can be justified on the basis of these observational findings is debatable.

Clinical bottom line

In critically ill patients with acute renal failure, there is no evidence to suggest that the use of loop diuretics reduces mortality, reduces length of ITU/hospital stay, or increases the recovery of renal function.