Building the Case Toward a Definitive Clinical Trial

Abstract

Abstract : Since its first reported use during the cholera pandemic in 1831, the potential pitfalls of sodium chloride (saline) as a resuscitative fluid for hypovolemic conditions have been described in numerous animal and human studies (1). Decrease in strong ion difference (SID) leading to hyperchloremic metabolic acidosis (2) and resultant effects on renal blood flow and renal insufficiency (3) and even potential immune dysfunction (4) are well-known phenomenon linked to saline-based resuscitation. Recent clinical studies have highlighted some of these deleterious effects. In a randomized, controlled, double-blinded, crossover study in 12 healthy volunteers, Chowdhury et al (5) demonstrated sustained hyperchloremia, reduced SID, and decreased mean renal artery velocity and renal cortical tissue perfusion when normal (0.9%) saline was administered compared with a more balanced crystalloid solution. In another single-center, prospective, sequential period study, Yunos et al (6) demonstrated significantly less acute kidney injury (AKI) and use of renal replacement therapy after the institution of a chloride restrictive resuscitation strategy when compared with a more liberal saline-based strategy used in the previous 6 months. Yet, despite these well-described deleterious effects, normal saline remains the most commonly used resuscitative crystalloid solution used today (7) and has often been the control fluid used in preclinical and clinical studies comparing resuscitation strategies. Aside from being inexpensive and compatible with many drugs and blood products, its common use likely reflects continued questions surrounding the true clinical significance of hyperchloremia.