Intense renal replacement therapy may lead to delayed extubation

Shilpa Sharma, Yvelynne P. Kelly et el published a study in Chest  comparing  intense vs usual renal replacement  therapy in patients  undergoing mechanical  ventilation. It was a secondary analysis of already completed ATN study.


Randomized clinical trials have failed to show benefit from increasing intensity of renal replacement therapy (RRT). RRT is associated with an increase in adverse events potentially secondary to small solute losses, such as phosphate. Authors looked at whether intense therapy leads to longer duration of mechanical ventilation.


The ATN study was a randomized multicenter trial of more- intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35 ml/kg per hour) versus less-intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20 ml/kg per hour) RRT in critically ill patients with AKI. It did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure. A total of 1124 patients were randomized.


  • Excluded all patients who were not on mechanical ventilation on the first day of study therapy.
  • The primary outcome was the time to first successful extubation off mechanical ventilation in patients from study initiation through study day 14. First extubation was defined as at least 48 consecutive hours independent of ventilator support.

Then the two groups were compared.


  • 907 patients were on mechanical ventilation on day 1 of the study.
  • Mean age of 59 ±15.3 years and a mean weight of 84.5 ± 19 kg.
  • The majority were men (70.4%) and 15.9% were black.
  • 27.3% were diabetic and 15.9% reported a known malignancy.
  • 21% had known congestive heart failure
  • 10% had a history of chronic hypoxemia.
  • There were no significant differences between individuals randomized to more-intensive and less-intensive RRT.


  • By 14 days, there was no difference in survival between the two treatment assignments (64.3 % of patients were alive in the more-intensive arm as compared to 63.9% in the less- intensive arm)
  • Patients randomized to more-intensive RRT had on average 2.07 ventilator-free days, compared to 3.08 days in those randomized to less-intensive RRT (P<0.001)

  • Among the 267 patients who were successfully extubated off ventilation for at least 48 hour in the two groups, re-intubation was later performed in 19% of patients in the more- intensive treatment arm compared to 10% in less-intensive arm (P=0.03)

  • There was a significantly greater reduction in serum phosphate (1.9 ± 0.1 mg/dL) in the more-intensive as compared with the less-intensive treatment group (1.0 ± 0.1 mg/dL; P <0.001). Baseline phosphate was similar.


Several possible mechanism  for  prolonged mechanical ventilation in intense RRT group

  1. Iatrogenic complications
  2. Depletion of vital nutrients with increased dose RRT
  3. Excessive loss of phosphate, a plausible contributor to diaphragmatic and intercostal muscle weakness


Trial was conducted in tertiary VA centers, mainly male patients, so cannot be generalized.

Trial was not designed to look for effect of phosphate. No data on phosphate supplementation. 



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