Since the 1920s it has been known that administration of chloride rich intravenous fluids, characterized by a reduced Sodium to Chloride strong ion difference (SID), causes a progressive metabolic acidosis. This iatrogenic hyperchloremic acidosis was particularly problematic in the era before lactate and ketone measurement was widely available, prolonging critical care stay and resulting in, often, unnecessary tests and therapies. During the 2000s a body of literature emerged supporting the hypothesis that hyperchloremia, defined as a plasma chloride of greater than 110mmol/l may be harmful. In a series of retrospective analyses, hyperchloremia was associated with increased mortality across a spectrum of disorders, including surgery and critical illness. Hyperchloremia was also associated with increased risk of kidney injury and the requirement for renal replacement therapy. There was also some data that hyperchloremia may be associated with reduced splanchnic blood flow.

A series of papers that looked at isotonic saline solution (ISS – 0.9% NaCl ), often referred to as “normal” saline, versus Plasmalyte 148 (PL) in Diabetic Ketoacidosis (DKA), demonstrated that ISS was associated with prolonged duration of stay in critical care, usually associated with persistent metabolic (hyperchloremic) acidosis. No studies to date have demonstrated superiority of ISS to PL Four major clinical trials – SALT ED, SMART, BaSics and PLUS– were conducted to compare outcomes of acute and critically ill patients randomized to either balanced salt solutions (sodium lactate products – Hartmann’s, Lactated Ringers or PL) or ISS. The first 2 studies demonstrated that ISS was associated with renal dysfunction and worse outcomes with sepsis. The BaSics and PLUS trials, in their initial reporting, showed no outcome differences. However, these trials were “catch” all ICU studies, including perioperative patients, patients pre-resuscitated with ISS, and, overall very little fluid was administered. The studies were grossly underpowered to detect outcome differences. However, subsequent systematic reviews and meta-analyses that included these data, and subgroup analyses of high risk patients, determined that fluid resuscitation with ISS was associated with worse 30 mortality, particularly in sepsis, and worse renal outcomes.

It is my view that, based on decades of research and experience, “normal” Saline (ISS) should not be used as a first line agent for fluid resuscitation in critical illness. I believe that the current international guidelines for the management of DKA are flawed in that they continue to recommend the administration of an agent that may well be toxic to patients, particularly when alternatives are easily available. Watch the video and make up your own mind.