Nov 292012
Does Normal Saline Cause Acute Renal Failure?

To internal medicine-trained physicians in the U.S., normal saline solution seems as harmless and healthy as mother's milk. Intensivists trained in anesthesia or surgery might more often mention normal saline's hypertonicity compared to blood, and its propensity to cause hyperchloremia, compared to lactated Ringer's or similar solutions. But who cares, really? Chloride is that number you can usually ignore in the chemistry panel -- almost always clinically irrelevant. Right?

Evidence suggests that in fact, excess chloride may be a little nastier than previously suspected. Normal saline infusion may worsen kidney perfusion, compared to PlasmaLyte, a crystalloid concoction that approximates human plasma in pH, osmolality, buffering capacity, etc. Normal saline also causes hyperchloremic metabolic acidosis, although any ill effects of that aren't clear.

So Nor’azim Mohd Yunos, Rinaldo Bellomo, Michael Bailey et al set out to see what would happen to rates of dialysis use at their Melbourne hospital if they replaced normal saline and all other high-chloride solutions with low-chloride ones.

See also: Resuscitation Fluids PulmCCM Review

What They Did

In this prospective, observational trial, the investigators first recorded lab values and other data on 760 patients admitted to a single ICU during a 6 month lead-in period in 2008, when normal saline flowed freely in usual critical care practice patterns.

They then abruptly cut off doctors' supply of normal saline and other high-chloride solutions. Physicians were forced to use Hartmann's solution (similar to lactated Ringer's), Plasma-Lyte, or low-chloride 20% albumin, unless they obtained attending specialist approval for normal saline. Patient data was again collected for 6 months.

What They Found
Patients received less chloride: an average of ~300 mmol less each, on average, in the intervention period (694-->496 mmol/patient). More interestingly, avoidance of normal saline and high-chloride solutions seemed to protect their kidneys:
  • Average serum creatinine rose by 0.25 per patient in the control period -- but only by 0.17 in the intervention period (p=.03).
  • The incidence of acute kidney injury (acute renal failure) was 14% in the normal saline period,  vs 8.4% with low-chloride solutions (p <.001).
  • 10% of patients needed renal replacement therapy during the normal saline epoch, but only 6% after normal saline was restricted (p = .005).
  • Patients receiving normal saline / high-chloride solutions had double the odds of RIFLE-defined acute kidney injury requiring dialysis, after adjustment for covariates (p = .004).

In-hospital mortality, length of stay in the hospital or ICU, and need for dialysis after hospital discharge were similar before and after normal saline restriction.

What It Means

Here's what all this stuff has in it:

Normal Saline vs Lactated Ringer's vs Plasma-Lyte

Normal Saline (0.9% NaCl) Lactated Ringer's Plasma-Lyte
Sodium (Na) 154 mmol/L 130 mmol/L 140 mmol/L
Chloride (Cl) 154 mmol/L 109 mmol/L 98 mmol/L
Potassium (K) none 4 mmol/L 5 mmol/L
Calcium (Ca) none 1.5 mmol/L none
Magnesium (Mg) none none 3 mmol/L
Lactate none 28 meq (28 mmol/L) none
Acetate none none 27 mmol/L
Gluconate none none 23 mmol/L
Tonicity Hypertonic (308 mOsm/L) Hypotonic (276 mOsm/L) Isotonic (294 mOsm/L)
Cost $2 / liter $4 / liter $12 / liter

Several intriguing small experiments in dogs and people suggest that chloride causes decreased kidney perfusion and may interfere with hemostasis. This interesting trial brings us a step closer to discovering any ill effects of normal saline and high chloride solutions. Administrators will cringe at the price difference between normal saline vs. lactated Ringer's and Plasma-Lyte, but this same group previously reported that overall fluid costs went down after restricting saline (most physicians switched to the Hartmann's solution). However, in that study -- but not here -- they also noted more episodes of alkalemia and slightly higher lactate levels in the no-normal-saline group.

Now, to better answer the question and eliminate the potential contributing secular, Hawthorne or "bundle" effects due to unblinding and the multiple simultaneous interventions in the present study, how about a randomized trial? Paging ANZICS and the Canadians!

Nor’azim Mohd Yunos, Rinaldo Bellomo, Michael Bailey, et al. Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults. JAMA 2012; 308(15): 1566-1572.

Resuscitation Fluids in the ICU: PulmCCM Review

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Normal saline: toxic to kidneys? Chloride solutions may cause renal failure