Tag Archives: hyperchloremia

Is 0.9% Saline Harmful in Critical Illness

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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.

Euglycemic Ketoacidosis associated with SGLT2 Inhibitors

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This tutorial looks at an emerging problem in medicine – iatrogenically induced eugylcemic ketoacidosis, associated with the use of SGLT2 (sodium glucose cotransporter 2) inhibitor drugs, also known as Flozins.

There is a global pandemic of metabolic disease caused by escalating ingestion of carbohydrate rich ultra processed food. This results in central obesity, hepatic steatosis (fatty liver) and insulin resistance: together these findings are labelled the “Metabolic Syndrome” (MetS). MetS is associated with systemic inflammation and atherogenesis. In many cases it progresses to Type 2 Diabetes (T2D), the majority of treatments for which increase adiposity and escalate insulin resistance. SLGT2 inhibitors are a relatively new class of drug that work by increasing excretion of ingested glucose by blocking the Sodium-Glucose symporter channel in the proximal tubule of the nephron. The result is mild natiuresis and glycosuria. These agents have been proven effective in the management of T2D and are emerging as effective treatments for other diseases such as congestive cardiac failure and nephropathy. As the name of each of these medications involves the suffix -flozin – they are commonly termed “Flozin” drugs.

One of the major problem with the use of Flozins in the community is failure to discontinue the drug when fasting or not consuming calories. Glucose will continue to be wasted, often generated by gluconeogensis, suppressing insulin secretion, resulting in lipolysis and ketosis. As blood glucose is low there is insufficient insulin present to prevent ketoacidosis. This is one of the causes of euglycemic diabetic ketoacidosis (EDKA). EDKA is associated with both ketoacidosis and hyperchloremic acidosis.

The treatment of EDKA is dextrose (to restore the Kreb’s cycle and suppress ketosis) and insulin – to put some control on the metabolic system. The patient may require a couple of liters of resuscitation fluid – preferably sodium lactate solution (Hartmanns or LR). The ketosis resolves rapidly, but the acidosis resolves slowly because it is principally driven by hyperchloremia. Patients who are being treated with SGLT2 inhibitors that are scheduled for surgery should stop taking these drugs 3 days pre-op. If they are continued inadvertently or surgery is emergent, then a dextrose infusion should be considered and ketones checked routinely.