KDIGO Clinical Practice Guideline for Acute Kidney Injury
NAC in critically ill patients: Recommendations and Rationale

Nac in critically ill patients

• 3.9.3: We recommend not using oral or i.v. NAC for prevention of postsurgical AKI. (1A)

Rationale

The above recommendation is based on an evaluation of the available literature on prevention studies with NAC in cardiovascular and abdominal vascular surgery, and liver transplantation.

The tables summarize the RCTs where either oral or i.v. NAC was compared to placebo; only studies containing a minimum of 50 patients in each study arm have been included. In addition, a recent meta-analysis is available,³⁷⁶ containing 10 studies involving a total of 1193 adult patients undergoing major surgery. Seven studies (1003 patients) evaluated the effects of NAC in patients undergoing cardiac surgery, and three of these (508 patients) exclusively studied patients with pre-existing renal impairment. Two studies (111 patients) evaluated the effects of NAC on patients undergoing abdominal aneurysm repair surgery and one study (79 patients) was of patients undergoing major abdominal cancer surgery. End-points in most of the studies were mortality, need for RRT, or varying increases in postoperative SCr concentrations compared to preoperative SCr values.

Suppl Tables 17 and 18 summarize the five studies where NAC was compared to placebo in patients undergoing cardiac surgery and who were not exposed to radiocontrast media.^377–381 All five studies analyzed the effects of NAC in patients with moderate, pre-existing renal functional impairment. Surgery included elective or emergency coronary artery bypass graft operations or heart valve surgery. NAC was given i.v. in most of the studies; mortality was evaluated at different follow-up times; either in-hospital or at 30 or 90 days. Only one study found a significantly lower mortality at 30 days.³⁷⁷ None of the studies found either a difference in need for RRT, or in AKI defined as variable changes in SCr after surgery. All studies were of A-level quality. Two relatively small studies evaluated the effects of NAC on patients undergoing abdominal aneurysm repair surgery^382,383 and did not find any protective effect on renal function.

Further, one meta-analysis³⁷⁶ did not find evidence that NAC used perioperatively can alter mortality or renal outcomes after major cardiovascular or abdominal cancer surgery when radiocontrast agents are not used. In none of the studies were significant treatment-related adverse effects of NAC reported. These reports suggest that NAC, in the context of cardiovascular surgery, is not associated with increased risk of mortality, surgical re-exploration, or allogeneic transfusion.

Only one single study has compared NAC to placebo in critically ill patients (Suppl Table 18).³⁸⁴ One hundred and forty-two ICU patients with new-onset (within 12 hours) of at least ≥ 30 consecutive minutes of hypotension and/or vasopressor requirement were randomized to receive either oral NAC or placebo for 7 days, in addition to standard supportive therapy. AKI was defined as ≥ 0.5 mg/dl ( ≥ 44 µmol/l) increase in SCr. Patients who received NAC had an incidence of AKI of 15.5%, compared to 16.9% in those receiving placebo (NS). There were no significant differences between treatment arms in any of the secondary outcomes examined, including incidence of a 50% increase in SCr, maximal rise in creatinine, recovery of renal function, length of ICU and hospital stay, and requirement for RRT. Mortality in both arms was 10%. Based on this single study, which is underpowered but did not show any beneficial effect on incidence of AKI, need for RRT, or patient mortality, we suggest not using NAC to prevent AKI in critically ill patients with hypotension.