Loop Diuretics in Acute Kidney Injury

A 65 year old woman underwent an elective mitral valve repair (MVR) and four vessel coronary artery bypass graft (CABG) procedure. Pre-operatively she was diagnosed with chronic kidney disease (CKD) secondary to hypertensive nephropathy, and chronic airway disease secondary to smoking. Her baseline creatinine was 275. Surgery was uneventful but in the post-operatively period she developed pulmonary oedema and worsening acute kidney injury (AKI). On day 2 her creatinine reached 420 and oliguria occurred (urine output < 0.5 ml kg-1 hr-1). Non-invasive respiratory ventilation provided adequate support and maintained a normal blood PaCO2 and pH, although her base excess drifted to -7 mmol l-1.Dopamine was administered at 2–10 μg kg-1 min-1, titrated to MAP ≧ 75 mmHg; pericardial pacing continued to maintain sinus rhythm at 60 bpm; her CVP was 14 mmHg and stable. Furosemide was started and given by a continuous infusion of 10 mg hr-1 after an initial bolus of 100 mg to try and help with diuresis.

Is there any evidence to support the use of loop diuretics in acute kidney injury?

Duncan Chambler

Acute kidney injury (AKI) is a common problem, with severe AKI (likely to require renal replacement therapy) affecting 6% of critically ill patients (1). Diuretic use is also common, being administered in approximately 70% of critically ill patients with AKI (2). The NCEPOD report of 2009, “Acute Kidney Injury: Adding Insult to Injury” (3) highlights the most common group being diagnosed with AKI are emergency admissions (90%).

Only 1% of AKI cases were planned admissions (the remaining 9% classified as inter-hospital transfers), although this unexpectedly low rate probably relates to inaccurate data coding that the NCEPOD report relied upon. The median patient age in this report was 83, with a strong bias for elderly patients as would be expected. The vast majority of these patients were admitted to general medicine or elderly care, with only 10% represented by postoperative cases.

Cardiothoracic surgery is a significant pathophysiological insult to the body. Along with many other measurable acute changes, AKI occurs with an incidence of between 7.7% and 28.1% after on-pump cardiac surgery (this wide range is due mostly to varying definitions used in studies for AKI). Severe AKI requiring renal replacement therapy is rare (1.4–3.0%). The prognosis of patients after cardiac surgery changes drastically if AKI develops, with mortality rates increasing from around 5% baseline to 45%. Risk of AKI varies between cardiac procedures, with valvular procedures conferring a 2.7-fold increase in risk compared to CABG procedures. (4) Notable, the patient described in this case had pre-existing renal disease and underwent combined CABG / MVR surgery, placing her in a high risk group for the development of post-operative AKI.

A relatively narrow and specific search of Medline (performed 15 April 2013), using the MeSH terms of “cardiac surgical procedures/”, “*acute kidney injury/” and “*furosemide/” (along with related MeSH terms and text words in titles and abstracts) results in 49 results. After scanning these abstracts, one review4 and one RCT5 were directly relevant to the clinical question. The review by Coppolino suggests furosemide by infusion at 10–20 mg hr-1 should be used if urine output remains < 0.5 ml kg-2 hr-1 despite optimised haemodynamics, reserving RRT for cases where this fails to maintain a normal physiological state. The RCT compared a bolus regime of furosemide (and dopamine infusion) against an infusion of furosemide (and dopamine infusion) and found significant reduction in the need for RRT in the continuous infusion group. However, the paper lacks any details regarding allocation, concealment, blinding, maintenance or intention-to-treat analysis.

Searching the Trip database (an EBM online resource: http://www.tripdatabase.com; search performed 15 April 2013) for articles relating to loop diuretics and AKI, without restricting to cardiac surgery, identified a systematic review and meta-analysis by Bagshaw (6). The authors conclude that loop diuretics for the management of AKI are not associated with improved survival rates, but do reduce the duration of RRT and increase urine output. They also highlight the lack of robust trials to answer the clinical question. An observational cross-sectional study from 1976 (7), found within the above Medline search, demonstrated 88% mortality in patients with AKI post on-pump surgery, increasing to 100% if RRT was required: this highlights the progress in peri-operative patient care over the last 38 years.

References
1 Uchino S, et al. Acute Renal Failure in Critically Ill Patients: A Multinational, Multicenter Study. Journal of the American Medical Association 2005; 294(7): 813-8.
2 Uchino S, et al. Diuretics and mortality in acute renal failure. Critical Care Medicine 2004; 32(8): 1669-77.
3 Steward J, et al. Acute Kidney Injury: Adding Insult to Injury. National Confidential Enquiry into Patient Outcome and Death 2009. http://www.ncepod.org.uk/2009aki.htm (accessed 25 July 2012).
4 Coppolino G, et al. Acute kidney injury in patients undergoing cardiac surgery. Journal of Nephrology 2013; 26(1): 32-40. Doi: 10.5301/jn.5000215.
5 Kunt AT, et al. Furosemide infusion prevents the requirement of renal replacement therapy after cardiac surgery. Anadolu Kardiyol Derg 2009; 9: 499-504.
6 Bagshaw SM, et al. Loop diuretics in the management of acute renal failure: a systematic review and metaanalysis. Critical Care and Resuscitation 2007; 9(1): 60-8.
7 Abel RM, et al. Etiology, incidence, and prognosis of renal failure following cardiac operations. Results of a prospective analysis of 500 consecutive patients. Journal of Thoracic & Cardiovascular Surgery 1976; 71(3): 323-33.