Normal saline solution is THE RESUSCITATION FLUID?!

My resident told me that resuscitation fluid is normal saline.  I was told to go write the order for normal saline at 100 cc/hr for my middle-aged severe sepsis pt with acute on chronic renal failure.  We were stopping it only if signs of difficulty breathing or shortness of breath developed.  I couldn’t remember why normal saline might not be the definitive answer for resuscitation, but when I asked about using lactated Ringer’s, I was told that normal saline is the resuscitation fluid of choice.  Dilutional hyperchloremic acidosis didn’t spring to mind; but, something didn’t sit right with me.

So, being the diligent 4th year medical student, I decided to educate myself by breaking down major papers on resuscitation fluid choices.  Much of my reading eventually honed in on the difference between normal saline and  “balanced” crystalloid solutions (e.g. Ringer’s lactate or Plasma-Lyte).  The science behind strong ion differences and the chemistry of fluids are complex and beyond the scope of this post.  But, my hope is to distill major studies on crystalloids–specifically, normal saline (“unbalanced” solutions) vs. “balanced” solutions.  This simplified approach detailed below should give us an idea of the themes that influence our fluid choices.  Furthermore, I have a feeling much of this relates to the glycocalyx and microenvironment/context/whatever you want to call it in which we administer resus fluids.  The study populations below are heterogeneous (i.e. some are healthy pts, some are septic pts), so no frank conclusions can be drawn.  I just thought it interesting that there’s so much normal saline-bashing happening recently.

A theme that seemed to be pervasive in my literature search: isotonic saline is nonphysiologic with a higher [Cl-] load compared to plasma; this may contribute to hyperchloremic metabolic acidosis, renal vasoconstriction, and a decrease in GFR.

(Full citations are at bottom of post)

Yunos et al. JAMA. 2012

Showed that period of higher Cl- use (i.e. like normal saline) was associated with greater adverse renal outcomes

–> Prospective, open-label study of 1533 pts admitted to the ICU

–> Compared control period (6 months of using chloride-rich fluids) vs. intervention period (6 months of using “balanced/physiologic” low chloride fluids)

* Keep in mind, normal saline has 154 mmol/L [Cl-] while lactated Ringer’s has 109 mmol/L [Cl-]

–> Primary outcomes of increased creatinine, increased incidence of AKI

–> Chloride restrictive strategy (the intervention period) was associated with lower creatinine, decreased incidence of AKI when compared to chloride-rich strategy, and a significant decrease in dialysis

Chowdhury et al. Ann Surg. 2012

Found greater adverse renal effects in healthy pts given normal saline rather than balanced solutions

–> Randomized, double-blind, cross-over study of 12 healthy adult males

–> Compared effects of normal saline infusion with effects of Plasma-Lyte (a “balanced solution”) infusion

–> Found the following adverse effects after normal saline: greater expansion of extracellular fluid volume, greater reduction in mean renal artery flow velocity, and greater reduction in renal cortical tissue perfusion

Shaw et al. Ann Surg 2012

Observed greater morbidity associated with normal saline in a population of abdominal surgery pts

–> Retrospective analysis of adult pts undergoing major abdominal surgery

–> 30,994 pts received only normal saline while 926 pt received only balanced fluid

–> Used a bunch of fancy models to find associations between fluid type given and endpoint of major morbidity defined as composite of one or more major complications

–> No significant difference between the two groups with rates of acute kidney injury (AKI), but normal saline group had increased dialysis (4.8% vs. 1%)

–> Mortality higher in the normal saline group (5.6% vs. 2.9%)

–> The authors conclude that the association between normal saline use and major morbidity appears to be stronger than chance; however, no explanation is clearly found

Karakala et al. Curr Opin Crit Care 2013

Briefly summarizes the aforementioned studies and points out many more interesting assocations with normal saline

–> An interesting, current review of different IV fluids in sepsis

–> Points out that normal saline/”physiological” fluid actually has 1.5x the [Cl-] as the human body

–> Cites Wilcox et al. experiment in dogs where rise in plasma [Cl-] demonstrated renal afferent vasoconstriction; infusion of chloride-containing solutions were associated with reduced renal blood flow

So, there you have it.  There’s no paucity of studies willing to look at the danger of normal saline.  Of particular interest to me was in the Karakala review.  They cited the difficulty in differentiating lactic acidosis (often in sepsis) from hyperchloremic metabolic acidosis (often 2/2 iatrogenic fluid loading).  It mentions that with the challenging  differentiation of the two pathphysiologies, we often volume load without knowing the etiology.  My question from looking at these studies has to do with the dogma of normal saline.  Its ubiquitous presence in the hospital makes it difficult to tease out the influences or systematic error in studies.  From a cursory glance, it seems that without a large RCT, the many studies may be hindered by our gut reaction to administer normal saline quickly and without pause.  As such, we don’t know if the RRT requirements are 2/2 the saline itself or preexisting tissue hypoperfusion states.

Chowdhury AH et al. A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and Plasma-Lyte 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg. 2012;256(1):18-24.

Yunos 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

Shaw et al. Major complications, mortality, and resource utilization after open abdominal surgery. Ann Surg 2012;255(5):821-829.

Karakala et al. Intravenous fluids in sepsis: what to use and what to avoid. Curr Opin Crit Care 2013;19(6):537-543.

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