From the Guidelines
Hyperchloremia is primarily caused by excessive chloride intake, particularly through the administration of chloride-rich intravenous fluids like normal saline (0.9% NaCl), as well as decreased chloride excretion and acid-base disturbances. The main causes of hyperchloremia include:
- Excessive chloride intake from intravenous fluids, medications such as ammonium chloride, certain antibiotics, and some total parenteral nutrition formulations 1
- Decreased chloride excretion in renal failure, particularly acute kidney injury, and with certain medications like carbonic anhydrase inhibitors (acetazolamide) 1
- Acid-base disturbances, such as metabolic acidosis, especially those with normal anion gap like renal tubular acidosis or diarrhea, which frequently presents with hyperchloremia as chloride rises to maintain electroneutrality 1
- Dehydration and water loss in excess of salt loss, which can concentrate chloride in the blood 1
- Endocrine disorders like hyperparathyroidism and adrenal insufficiency, which may also cause hyperchloremia 1
The use of normal saline (0.9% NaCl) has been shown to cause hyperosmolar states, hyperchloremic acidosis, and decreased renal blood flow and glomerular filtration rate, which can exacerbate sodium retention and lead to fluid overload 1. A more recent study published in 2023 found that patients who received 0.9% saline compared with lactated Ringer’s (LR) in hemorrhagic shock experienced a higher incidence of hyperchloremic metabolic acidosis, electrolyte derangements, dilutional coagulopathy, and higher overall volume requirements for adequate resuscitation 1.
To minimize the risk of hyperchloremia, it is recommended to use balanced crystalloid solutions instead of normal saline when appropriate, and to monitor kidney function and acid-base status closely. This approach can help reduce the incidence of hyperchloremic metabolic acidosis, electrolyte derangements, and other complications associated with excessive chloride intake 1.
From the Research
Causes of Hyperchloremia
- Hyperchloremic metabolic acidosis is the result of chloride retention, excessive loss of sodium relative to chloride, or excessive gain of chloride relative to sodium 2
- Hyperchloremic metabolic acidosis of renal origin results from a defect in renal tubular acidification mechanism, which can consist of an altered tubular proton secretion or bicarbonate reabsorption capability 3
- Renal tubular acidosis (RTA) can lead to hyperchloremic metabolic acidosis, and its pathophysiologic mechanisms include renal mass reduction, hyperkalemia, hyperparathyroidism, graft rejection, immunologic diseases, and some drugs such as renin-angiotensin-aldosterone blockers, and calcineurin inhibitors 3
- Iatrogenic hyperchloremia can occur in hospitalized patients due to the administration of intravenous (IV) fluids, medication diluents, and total parental nutrition 4
- Hyperchloremia can also occur in patients with chronic renal failure, particularly those with tubular dysfunction 5
- Severe hypernatremia and hyperchloremia can occur in patients with multiple myeloma, especially when treated with intravenous saline infusions in a state of poor oral fluid intake 6
Underlying Mechanisms
- Defect in renal tubular acidification mechanism 3
- Tubular dysfunction in chronic renal failure 5
- Damage to the distal tubules in the kidneys 6
- Administration of unbalanced IV fluids, medication diluents, and total parental nutrition 4