early RRT in ICU increases risk of CLABSI

  • related: Nephrology
  • tags: #literature #icu #nephrology

Start RRT in ICU patients when:

  • mechanically ventilated or on pressors AND
  • BUN over 112 but before 140
  • oliguria for 72 hours (most important)
  • acute pulmonary edema
  • pH less than 7.15
  • K over 6

Early RRT initiation leads to double risk of CLABSI, no benefit to survival or liberation from vent, and took longer to liberate from RRT.

After presenting with septic shock and acute hypoxemic respiratory failure from a necrotizing skin and soft-tissue infection, the patient has developed stage 3 acute kidney injury (AKI) as graded with the Kidney Disease: Improving Global Outcomes guidelines. In addition to evaluating the patient for potential causes of AKI, critical care physicians also consider if and when RRTs should be initiated. Common indications for emergently instituting RRT include immediately life-threatening forms of metabolic acidemia, hyperkalemia, volume overload, uremia, or toxic ingestions with compounds potentially removed with dialysis. However, most adults critically ill with AKI never develop any of these immediately life-threatening emergencies, and work has been done to evaluate whether initiating RRT early in these patients without these emergencies improves outcomes.

In the AKIKI trial published in 2016, adults critically ill with stage 3 AKI and receiving invasive mechanical ventilation or vasopressors, but without any immediately life-threatening complications of renal dysfunction (similar to the patient presented here), were randomly assigned to an early or immediate initiation of an RRT strategy vs a delayed strategy. In the delayed strategy group, RRT was not started unless the patient developed any one of the following: blood urea nitrogen (BUN) level greater than 112 mg/dL (39.98 mmol/L), potassium level greater than 6 mEq/L (6 mmol/L), pH less than 7.15, or acute pulmonary edema due to fluid overload requiring more than 5 L/min of oxygen flow or an FIO2 greater than 0.5 if receiving invasive ventilation despite diuretics. With this delayed strategy, approximately half of the patients in this group never developed any of these criteria and never needed RRT. The risk of catheter-related bloodstream infection in the early initiation group was double that in the delayed initiation group (10% vs 5%) (choice B is correct). In the AKIKI trial, early initiation of RRT did not result in increased survival or a shorter time to liberation from invasive mechanical ventilation (choices A and D are incorrect). Interestingly, patients randomly assigned to the early initiation of RRT took longer to recover renal function, as measured with adequate urine output without the need for RRT, than did patients randomly assigned to a delayed strategy (choice C is incorrect).

The STARRT-AKI trial, which is the largest trial attempting to answer this question and in a patient population similar to that in the AKIKI trial, similarly showed no survival benefit with early RRT. The STARRT-AKI trial also showed that early RRT was associated with an increased risk of prolonged RRT need compared with a delayed approach.

The definitive trial addressing this question is the STARRT-AKI trial, which randomly assigned 3,019 patients (2,927 analyzed) in the ICU with Kidney Disease: Improving Global Outcomes stage 2 or 3 kidney injury and an elevated serum creatinine level to either “accelerated” renal replacement therapy (ie, within 12 h of meeting trial enrollment criteria) or a “standard” approach, which meant waiting for either a traditional indication for renal replacement therapy (ie, any of arterial pH ≤7.20, bicarbonate level ≤12 mEq/L [12 mmol/L], potassium level ≥6 mEq/L [6 mmol/L], or symptomatic volume overload leading to respiratory failure) or for the passage of 72 h without improvement in kidney injury. The key findings of the STARRT-AKI trial were that there was no evidence for a mortality difference (43.9% vs 43.7%; relative risk, 1.00; 95% CI, 0.93-1.09), but patients assigned to the accelerated strategy were more likely to still be receiving renal replacement therapy at 90 days (10.4% vs 6.0%; relative risk, 1.74; 95% CI, 1.24-2.43). Adverse events were also more common in the accelerated strategy group (23.0% vs 16.5%, P < ), primarily because of hypotension and hypophosphatemia (choice B is correct).

A key finding of trials in this area is that many patients with oliguric kidney injury will either improve or undergo transition in goals of care that exclude dialysis. On the basis of current available data, in this patient a delay of up to 72 h is reasonable and appropriate. Notably, most trials initiated renal replacement therapy at 72 h in the setting of persistent oliguric kidney injury, and the AKIKI 2 trial evaluated further delays beyond 72 h and found them likely harmful. As a consequence, delays of up to 72 h (assuming no formal indications for initiation of renal replacement therapy are met) are appropriate (choice D is incorrect).

The AKIKI 2 trial provides further evidence to guide practice. The AKIKI 2 trial, again, excluded the same patients with life-threatening conditions related to renal dysfunction, similar to the AKIKI trial. The AKIKI 2 trial focused specifically on initiating RRT in a “delayed” strategy when the BUN level became greater than 112 mg/dL (39.98 mmol/L; similar to AKIKI) or when the patient had 72 h of oliguria (urine output <0.3 mL/kg/h) vs a “more delayed” strategy in which RRT was not initiated until the BUN level was greater than 140 mg/dL (49.98 mmol/L). There was no difference between groups in the primary outcome of RRT-free days; however, in a secondary analysis, the “delayed” strategy was independently associated with increased survival, suggesting a possible benefit to starting RRT when the BUN level increases above 112 mg/dL (39.98 mmol/L) or the patient has had 72 h of oliguria. Of note, the patient discussed here has not had a BUN level greater than 112 mg/dL (39.98 mmol/L), nor has he had 72 h of oliguria, and he would not have been included in the AKIKI 2 trial.12345

Footnotes

  1. SEEK Questionnaires ↩

  2. Gaudry S, Hajage D, Martin-Lefevre L, et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Lancet. 2021;397(10281):1293-1300. PubMed ↩

  3. Gaudry S, Hajage D, Schortgen F, et al; AKIKI Study Group. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122-133. PubMed ↩

  4. Kellum JA, Romagnani P, Ashuntantang G, et al. Acute kidney injury. Nat Rev Dis Primers. 2021;7(1):52. PubMed ↩

  5. STARRT-AKI Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group; et al. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med. 2020;383(3):240-251. PubMed ↩