Description of the condition
Acute kidney injury (AKI) is a complex clinical entity characterised by an abrupt decline in kidney function (Mehta 2004; Mehta 2007). AKI incidence among adults admitted to intensive care units ranges from 5% to 20% (Joannidis 2005); incidence escalates to 10% in children (Schneider 2010). Despite its potential to be reversed, AKI is associated with high morbidity and mortality, and AKI-related mortality substantially increases among people with multi-organ failure, sepsis, or who are receiving renal replacement therapy (RRT) (Metnitz 2002; Sutherland 2010). More than 70% of people with AKI need renal support therapies. Despite advances in clinical care, people with AKI have high risks of mortality and morbidity, and require significant health care resources (Sutherland 2010; Uchino 2005).
Description of the intervention
Continuous RRT (CRRT) is an extracorporeal blood purification therapy, intended to support impaired kidney function. CRRT removes fluid slowly over prolonged periods (Foland 2004; Gibney 2008; Goldstein 2001; Mehta 1999); removes higher molecular weight solutes efficiently (Brunnet 1999; Clark 1999; Liao 2003; Ronco 2002; Sieberth 1995); and confers beneficial haemodynamic stability effects. CRRT modalities are defined by their main solute clearance mechanism. These are convection (continuous venovenous haemofiltration, CVVH), diffusion (continuous venovenous haemodialysis, CVVHD), or a combination of both convection and diffusion (continuous venovenous haemodiafiltration, CVVHDF) (Palevsky 2002). Several interventions have been used over the past three decades with the aim of improving the poor prognosis of people with AKI. A significant factor that may impact on CRRT outcomes is timing of treatment initiation (Intensity of CRRT for AKI will be investigated in a separate Cochrane review by the same author team; Fayad 2013).
Teschan 1960 reported improved survival rates relating to CRRT timing in patients commencing dialysis with low blood urea nitrogen. Observational studies and randomised controlled trials (RCTs) in CRRT have shown that early initiation of RRT may provide improved outcomes for critically ill patients with severe AKI (Bagshaw 2009; Liu 2006). However, an earlier study did not support these benefits (Bouman 2002). The effects of early versus late initiation of dialysis support for AKI on outcomes therefore remain unclear.
The optimal time (early versus late) for CRRT initiation to improve AKI outcomes remains unclear. The indication to start CRRT for people in intensive care is most often based on clinical and biochemical criteria. In our review, we will assign definitions given in included studies in relation to early and late initiation of CRRT.
How the intervention might work
A hypothesis that timing of RRT commencement may affect survival emerged from animal and human studies over the past decade. Animal studies investigating sepsis (Mink 1995) and pancreatitis (Yekebas 2002) suggested beneficial effects on physiologic and clinical endpoints when haemofiltration was started early, simultaneously, or two hours after injury. Several observational studies investigated the effect of timing in patients with AKI post trauma indicated improved survival in early haemofiltration (Gettings 1999), the same was found in patients with AKI post cardiac surgery (Demirkilic 2004; Elahi 2004). RCTs found in patients with pancreatitis that the survival was also significantly better in patients who received early haemofiltration (within 48 hours after onset of abdominal pain) than in the group with late haemofiltration (96 hours after onset abdominal pain) (Jiang 2005), while another RCT failed to demonstrate these advantages (Bouman 2002).
Why it is important to do this review
Observational studies that assessed CRRT timing (early versus late) have reported inconsistent results: earlier studies indicated significant improvements in survival and renal recovery; yet others, including a RCT, did not find these benefits. Given these inconsistent results, and the possibility of improving outcomes for ICU patients, we plan to investigate the relationship between CRRT timing and outcomes for people with AKI. Review evidence will have direct relevance to decisions about optimal CRRT timing to improve survival in critically ill patients with AKI.