ABSTRACTS from 16th International COnference on ... - CRRT Online

Saline is Really Bad for You. Hard to Believe. Impossible to Ignore!
John A. Kellum MD
10:00-10:15
Thursday, February 16
Educational Objectives:
To discribe underlying mechanisms of hyperchloremic acidosis
To review existing evidence for the effect of hyperchloremia on innate immunity
To review existing evidence for the effect of hyperchloremia on clinical outcomes
Content Description:
Metabolic acidosis induces cytokine expression and immunomodulation
Fluid resuscitation with hyperchloremic solutions causes metabolic acidosis and a potentially important consequence
of acidosis is its effect on the immune response. Several studies <strong>from</strong> our laboratory and elsewhere have
documented the effects of decreased extracellular pH on the synthesis and release of inflammatory mediators.
Different degrees of metabolic acidosis have been shown to cause induction of inflammatory markers such as
Nitric oxide (NO), interleukins (IL-6 and IL-10). HCA have been shown to induce tumor necrosis factor (TNF)
synthesis and release, as well as nuclear factor kappa-B (NF-ÎB) DNA binding, suggesting that the overall effects
of hyperchloremia appear to be pro-inflammatory. Jensen and colleagues exposed macrophages to lactic acid and
found that TNF secretion was increased secondary to increased gene transcription. In addition acidosis induces
inflammatory response through its effect on catecholamine synthesis.
Metabolic acidosis adversely influences survival
Although it is currently uncertain whether there is a true cause-effect relation between HCA and adverse clinical
outcomes, metabolic acidosis in critically ill patients is a powerful marker of poor prognosis. Metabolic acidosis
may increase inducible nitric oxide synthase (iNOS), and this may lead to vasodilation and shock. We have previously
demonstrated that HCA, induced by hydrochloric acid infusion, significantly reduced systemic mean
arterial pressure in normotensive, septic animals. In a study using an endotoxic shock model in rats, we demonstrated
that saline resuscitation was associated with a significantly shorter survival time compared to a more
physiologic fluid containing starch in a balanced electrolyte solution. Furthermore, survival time was correlated
with the decrease in pH and negatively correlated with the increase in serum chloride following initial resuscitation.
Hyperchloremia associated with saline-based solutions has been shown to cause hypotension, decrease
splanchnic mucosal perfusion, glomerular filtration, and cause coagulopathy. Emerging data suggest that hyperchloremia
aggravates AKI though mechanisms are unclear.
Suggested Reading:
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2. Kellum JA. Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: improved short-term survival and
acid-base balance with Hextend compared with saline. Crit Care Med 2002; 30:300-305.
3. Waters JH, Miller LR, Clack S, Kim JV. Cause of metabolic acidosis in prolonged surgery. Crit Care Med 1999;27:2142-
6.
4. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloremic acidosis in patients
undergoing gynecologic surgery. Anesthesiology 1999;90:1265-70.
5. Kellum JA, Song M, Venkataraman R. Effects of hyperchloremic acidosis on arterial pressure and circulating inflammatory
molecules in experimental sepsis. Chest 2004; 125:243-248.
6. Pedoto A, Caruso JE, Nandi J, Oler A, Hoffmann SP, Tassiopoulos AK et al. Acidosis stimulates nitric oxide production
and lung damage in rats. Am J Respir Crit Care Med 1999; 159(2):397-402.
7. Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH et al. Natural history and course of
acquired lactic acidosis in adults. DCA-Lactic Acidosis Study Group. Am J Med 1994; 97:47-54.
8. Wilkes NJ, Woolf RL, Powanda MC, Gan TJ, Machin SJ, Webb A et al. Hydroxyethyl starch in balanced electrolyte solution
(Hextend)-- pharmacokinetic and pharmacodynamic profiles in healthy volunteers. Anesth Analg 2002; 94:538-544.
9. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The effect of intravenous lactated Ringer's solution versus
0.9% sodium chloride solution on serum osmolality in human volunteers. Anesth Analg 1999; 88:999-1003.
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