| EPO in CABG | EARLYARF |
---|---|---|
Sample size | 71 (EPO: 36, placebo: 35) | 162 (EPO: 84, placebo: 78) |
Patient population | Elective CABG | Aim: ICU patients at high risk of AKI; Obtained: critically ill patients |
Study design | Prospective randomised double-blind, placebo-controlled trial | Prospective randomised double-blind placebo-controlled, trial |
EPO type and dose | 1 dose preop: 300 U/kg EPO or normal saline IV | 2 doses: EPO-beta 500 U/kg to max 50,000 U or normal saline IV |
Inclusion criteria | > 18, elective CABG | ↑ in GGT and ALP urine concentration product > 46.3 |
Exclusion criteria | Emergent CABG, pre-existing AKI, on RRT, uncontrolled HT, nephrotoxic drugs within 3 days of op, previous use of EPO | < 16 yr, no IDC, hematuria, rhabdomyolysis, myoglobinuria, polycythemia, cytotoxic chemo, RRT or needs in 48 hr, stay ≤24 hr, survival ≤72 hr, prior RIFLE "failure" |
Measurements | Baseline SCr preop and 24, 72, and 120 hr postop | Baseline creatinine: various versions of preop/pre-ICU creatinine, including lowest on ICU admit/last ICU creatinine/minimum at 12 mo. Blood for creatinine and Cyst C and start for 4/24 creatinine clearance |
Age (mean) | 66.7 | 61.6 |
Study groups: EPO vs. placebo | Baseline and intraoperative: no significant differences, most OPCABG (77%) (+3valves in EPO group) | EPO group older (p = 0.011) and ↑ likelihood for sepsis (p < 0.05). More placebo patients had AKI (not significant) |
Primary outcome | Incidence of AKI after CABG | A priori: Average % plasmaCr↑ from baseline over 4-7 days. |
Secondary outcomes | Changes in SCr and eGFR (first 5 days postop), ICU and hospital LOS, in-hospital mortality | AKIN & RIFLE AKI definitions, plasma cystatin C, need for dialysis, death within 7/30/90 days; |
AKI: Definition | ≥50%↑ in SCr from preop baseline | AKIN (creatinine and UO) and RIFLE (creatinine) definitions |
AKI: Proportion | EPO 8%, placebo 29%; p = 0.035 | AKIN creatinine: EPO 45.2%, placebo 47.4%; RIFLE creatinine: EPO 23.8%, placebo 19.2%; AKIN UO: EPO 70.2%, placebo 51.3% (p = 0.016) |
Results | %SCr↑ at 24 hr: EPO 1 ± 3, placebo 15 ± 7 (p = 0.04). %SCr↑ at 120 hr: EPO 7 ± 4, placebo 27 ± 8 (p = 0.01). %eGFR↓ at 24 hr: EPO 3 ± 3, placebo -5 ± 4 (p = 0.04). %eGFR↓ at 120 hr: EPO -4 ± 3, placebo -13 ± 5 (p = 0.01) | No significant difference in 1° outcome or 2° outcomes except AKI (AKIN UO). Of randomised pts without AKI initially (n = 104) EPO patients had higher %plasmaCr↑: EPO 8.5 ± 27(n = 61), Placebo -4.6 ± 18 (n = 47; p = 0.004). |
Onset of injury | Initiation of CABG operation | Heterogenous. Time of injury estimated for subdivision analysis. Samples from 6-12 hr after putative insult more predictive for AKI (AUC = 0.69), dialysis, and death. |
AKI mechanism | CVS compromise, CPB exposure | Heterogenous |
Safety | No symptomatic thrombosis or other adverse events in EPO patients | No evidence for ↑intravascular thrombosis. EPO not associated with ↑ in adverse events. |