0.9% Saline vs. Plasma Lyte (Registered Trademark)148 for Fluid Intervention Trial in Major Surgery Patients (The SPLIT- Major Surgery study)

The administration of intravenous crystalloid fluid (also known as fluid therapy) is a ubiquitous intervention in patients undergoing surgery. Worldwide, the most commonly used crystalloid fluids available for patients undergoing major surgery include Saline (0.9%) or the balanced fluid solutions - Hartmann’s and Plasmalyte. Choice of fluid therapy is based frequently dependent on geography, and choice of fluid amongst anaesthetists at Austin Hospital is similar to worldwide practices. Saline has been used in clinical practice for fluid therapy since the late 1800s. While it is the most commonly used IV fluid in the world recent data raise the possibility that it might increase the risk of developing kidney damage in acutely unwell patients compared to fluids with lower concentrations of chloride such as Plasmalyte. While this increased risk of kidney damage with the use of saline is plausible, current data are insufficient to recommend clinical practice change and data from an interventional trial are urgently needed. However, the design of such a Trial requires sufficient pilot data to establish feasibility, safety power calculations and define an optimal study protocol. This study aims are to provide high quality pilot data in a rapid time frame to address this important question and to help decide whether a pivotal randomized controlled trial is justified. Thus, all patients undergoing surgery at Austin Hospital will be assigned to receive either Saline (0.9%) or the balanced crystalloid solution Plasmalyte as the primary crystalloid fluid in a blinded fashion during two study periods. The study will be conducted over a 4-month period allowing including two periods of 6 weeks each where all patients will receive the intervention, with a three week wash-in and a three week wash-out period for each group. Blinded study fluid will be used for all crystalloid therapy in all participants. Austin Hospital staff specialists in anaesthesia agree that on the basis of current evidence, Saline (0.9%) and Plasmalyte are equally acceptable for crystalloid fluid therapy in every situation requiring major surgery with the exclusion of surgery for liver transplantation, renal transplantation and patients with raised intracranial pressure, where specific hospital perioperative fluid protocols are used in these settings. Both Saline (0.9%) and Plasmalyte will be available for open-label administration in the rare situations, where, in the opinion of the treating anaesthetist or clinician, there is a clinical indication for one fluid or the other. This may occur, for example, in the setting of severe acidosis where the higher chloride content of saline may make this fluid problematic because it may increase the severity of such acidosis. All adult patients who receive blinded or open-label fluid during one of the two-month study blocks will be analysed. The primary outcome will be the proportion of patients with kidney injury or failure based on established criteria. Secondary outcomes will include delta creatinine (the difference between baseline and peak creatinine), serum electrolyte levels, bicarbonate level, requirement for renal replacement therapy, complications and in-hospital mortality. All of the data required for this study are collected routinely as part of standard clinical care and/or quality assurance activities. The study will establish the pilot feasibility, safety and preliminary efficacy evidence base for the design of a large interventional trial to inform clinicians looking after major surgery patients as to whether Saline (0.9%) or Plasmalyte or solution is the preferred crystalloid fluid in this setting. Hospitals involved: Austin Hospital Number of participants: Given the current theatre workload at Austin Hospital, approximately 1000 participants will be recruited in each group. A total of 2000 participants are expected.