7000 patients were analysed to compare the use of 6% HES 130/0.4 (carried in 0.9% saline) against 0.9%saline for fluid resuscitation (not maintenance fluid) of almost all comers to the ICU. The exclusions were fairly predictable – pre-existing need for RRT, ICH, predicted non-survival to 90 days and anyone who had already been given significant quantities of HES prior to study enrollment. There were some interesting fingings.
First off, the study was powered to detect a >3.5% difference in mortality at 90 days, with an expected mortality of 26%. As it turned out, the actual mortality was lower than expected, at about 17%. There was also a higher than expected cohort of elective surgical patients in the study population, accounting for about 23% of each study group.
The trial failed to identify a significant difference in the primary outcome of mortality at 90 days.
In terms of secondary and tertiary outcomes, for the 6% HES group there was:
less total volume of study and non-study fluid given, particularly in the first 24 – 48 hours of admission
higher CVP acheived
less use of vasopressor
no difference in the occurrence of new organ failure in either group, except for a higher bilirubin in the HES group and a higher incidence of CVS failure in the 0.9% saline group (possibly related to the higher use of vasopressor in this group)
no difference in ICU length of stay or duration of mechanical ventilation
a greater use of blood products
less patients acheiving RIFLE-R or I criteria, but a greater, non-significant number acheived RIFLE-F criteria
higher creatinine levels
greater use of RRT
higher incidence of adverse effects, mostly pruritis
Now we can sit back and look forward to the ensuing analyses, criticisms and rebuttals. There will be those that argue that between CHEST and the recently published 6S trial (a sicker population, but with a similar outcome profile for 6%HES versus Ringer’s Lactate, n=804) that HES products are now dead and buried. However, there will probably also be an equally vociferous mob who will counter that the CHEST trial actually shows that the lower molecular weight and molar substitution hydroxy ethyl starches are in fact no worse than crystalloid, given that despite a just about higher incidence of needing to start RRT (p =0.04, RR 1.21 95%CI 1.0 -1.45), there was no difference in 90 day mortality. Can’t wait for the next critical care conference (“Aha”, I hear you cry, “have you heard about SMACC 2013?”).
In other research news, here are a few ANZICS CTG trials that you can look forward to being kicked off in a unit near you over the coming months:
TRANSFUSE – Aim is to determine if transfusion of the freshest available RBC in critically ill patients compared to standard care decreases patient mortality. Target sample size = 5,000. Primary outcome = 90 day mortality. Secondary outcomes will include organ failures and duration in ICU and of mechanical ventilation. Initially being rolled out in Victoria in October, it aims to subsequently include ICUs in Australia, New Zealand, Ireland and Finland.
CLIP – Cryopreserved vs. Liquid Platelets for Surgical Bleeding. Aim is to determine the safety and efficacy of cryopreserved platelets (-80C) versus standard platelet preparations (which have a 5 day shelf life) for managing bleeding in high-risk surgical patients, while facilitating the recommended PRBC to PLT transfusion ratios. Target sample size = 90 patients across 3 centres in Queensland. Planning to be completed by December 2013.
The IRONMAN Study – Intravenous iRon or placebO for aNaeMiA in INtensive Care: A Randomised Controlled Study. (Great name Ed!). Aim is to see if IV iron therapy can reduce the need for PRBC transfusion in ICU patients who are anaemic. Not sure what the target sample size or proposed start date is.