Timing of renal replacement therapy in septic shock


S.D. Barbar, R. Clere-Jehl, A. Bourredjem, R. Hernu et el  published a study about timing of renal replacement therapy in patients with septic shock and acute kidney injury. 

BACKGROUND

Patients hospitalized in the intensive care unit (ICU) for septic shock frequently develop acute kidney injury and is associated with high mortality.  When to provide  the renal replacement therapy in such patients remains an elusive answer.  Recently, two randomized, controlled trials comparing an early strategy with a delayed strategy for the initiation of renal-replacement therapy reported conflicting results.  Study by Gaudry S, Hajage D, Schortgen F et el showed no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients.  Study by Zarbock AKellum JA Schmidt C et el  showed early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days.

It is widely accepted that if there are life-threatening complications of acute kidney injury, such as hyperkalemia or metabolic acidosis, renal-replacement therapy should be initiated immediately.

STUDY

It was multi-center, randomized, controlled trial comparing Early (within 12 hours) Versus late (a delay of 48 hours) Renal replacement therapy in adult patients admitted with septic shock who developed acute kidney injury(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).

PATIENTS

18 years of age or older, who were admitted to the ICU in the early phase of septic shock who developed renal failure.

WHERE

29 Intensive Care Units (22 university teaching hospitals and 7 general hospitals) in France.

INTERVENTION

Patients in early intervention group received renal replacement therapy within 12 hours of developing renal failure. The delayed group was closely monitored for the following

1. Hyperkalemia (potassium level >6.5 mmol per liter),

2. Metabolic acidosis (pH <7.15), or

3. Fluid overload (extravascular fluid overload that was refractory to diuretics, with pulmonary edema).

These patients would receive intermediate renal replacement therapy.

TRIAL OUTCOMES
The primary outcome was death from any cause at 90 days after randomization. Secondary outcomes were death at 28 days and at 180 days; the number of days free of renal-replacement therapy, mechanical ventilation, and vasopressors at 28 days after randomization; the length of stay in the ICU and in the hospital; adverse events during the entire ICU stay, with a focus on the complications potentially related to acute kidney injury or renal-replacement therapy during the first 7 days after enrollment; fluid balance in the first 7 days after enrollment; the need for emergency renal-replacement therapy in the delayed strategy group. 

RESULTS

The early initiation of renal-replacement therapy did not result in lower mortality at 90 days than the delayed strategy; 138 of 239 patients (58%) in the early-strategy group died and 128 of 238 patients (54%) in the delayed-strategy group died (P = 0.38).

In delayed group, emergency renal replacement therapy was required  in 41 patients (17%); 28 of these patients died. Reason for emergent renal replacement therapy was metabolic acidosis and hyperkalemia. 

There was no significant difference between the groups in fluid balance in the 24 hours before randomization, in the 48 hours after enrollment, or at 7 days.

29% of the patients in the delayed-strategy group did not require renal-replacement therapy because they had spontaneous recovery of renal function.

Mortality was higher among patients assigned to the delayed-strategy group who met criteria for emergency renal-replacement therapy (68% [28 of 41 patients]) than among those who did not meet the criteria.

BOTTOMLINE

We can wait to initiate renal-replacement therapy in patients with acute renal failure in septic shock as many of these patients spontaneously recover.  Delaying therapy does not increase mortality. Early renal replacement therapy may expose patients to risks associated with renal replacement therapy. 

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