October - 2018
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Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis
New Eng J Med, 2018, 379:1431-1442
In this weeks NEJM we have the IDEAL-ICU Trial, examining the effect of timing of renal-replacement therapy for patients with severe sepsis and severe acute kidney injury.
The initiation of RRT is accepted if there are life-threatening complications of AKI (eg hyperkalaemia, acidosis), however timing in the absence of these is less clear. In 2016 we had 2 RCTs that shed light on this;
So very different outcomes from the two studies. The two studies had fairly similar entry criteria, and mortality rates (different time points 90 vs 60 days), the time to delayed RRT was different (25.5 hrs vs 57 hrs), the modes were different (CRRT vs predominantly IHD), and the proportion that didn’t receive RRT in the delayed group were different (9% vs 50%). Did the first study show a treatment benefit because they used CRRT, i.e. avoiding the cardiovascular effects of intermittent ? Because they gave “delayed” treatment 30-hrs earlier, or because >90% of delayed received the therapy? Is it simply the single centre limitation?
Bring on the IDEAL-ICU Trial;
So, overall, in a homogeneous population of patients with severe AKI in the early phase of septic shock, the initiation of early RRT was not associated with improved 90-d mortality or secondary outcomes compared to delayed RRT. Delayed RRT did result in 38% of patients not receiving RRT.
The authors provide a good last word “risk of death is not increased if renal replacement therapy is postponed for at least 48 hours, as long as care id taken to identify patients in whom criteria for emergency renal replacement therapy are likely to be met”
Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial.
In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days.
The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients).
Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy.
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