Safety and efficacy of 6% hydroxyethyl starch in patients undergoing major surgery: The randomised controlled PHOENICS trial.

BACKGROUND

Hydroxyethyl starch (HES) is often used for maintaining vascular volume during major surgery. Long-term high-dose HES in septic patients promotes renal injury, whereas meta-analyses of current HES products in surgical patients do not show such effects.

OBJECTIVE

We studied if the peri-operative use of HES is noninferior to crystalloids in terms of acute kidney injury. Secondary outcome was the noninferiority of HES on worsening of renal injury and/or the incidence of a composite endpoint of major complications and mortality until postoperative day 90.

DESIGN

Randomised double-blind trial in patients undergoing elective abdominal surgery with expected blood loss at least 500 ml.

SETTING

Multicentre trial at 53 study sites in 10 European countries.

PATIENTS: One thousand nine hundred and eighty-five (HES 977, crystalloid-only 981) patients aged 40 to 85 years with ASA status II-III.

INTERVENTION: Either 6% HES 130/0.4 or a crystalloid solution. Dosing was guided by mean arterial pressure and/or routine haemodynamic variables.

MAIN OUTCOME MEASURE: Change from pre-operative to lowest cystatin C-based eGFR during the first 3 postoperative days. Key secondary outcome was a composite endpoint of mortality and major postoperative complications after 90 days.

RESULTS

Mean change in eGFR from baseline to minimum was -3.4 ± 17.7 ml min -1  1.73 m -2 in HES patients and -1.0 ± 17.1 ml min -1 1.73 m -2 in crystalloid-only patients ( P  < 0.001 for noninferiority). The key secondary endpoint occurred in 35% of patients in each group. There were no clinically relevant differences in any safety endpoint including 90-day renal function. Any cause mortality-difference until the end of 1-year follow-up was not significantly different (8.6% in HES and 10.1% in crystalloid patients).

CONCLUSION

Peri-operative use of HES was noninferior to crystalloids in short-term renal function or a composite of mortality and major complications at 90 days. PHOENICS provides robust evidence that peri-operative in-label use of HES is well tolerated.

TRIAL REGISTRATION AND FUNDING: EudraCT no. 2016-002162-30, clinicaltrials.gov ID NCT03278548.