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In a study from England published ahead of print in Annals of Surgery, healthy volunteers given two liters of so-called "normal" saline intravenously showed signs of decreased kidney perfusion and increased fluid retention compared to infusion of a balanced salt solution. The work builds on previous research suggesting that normal saline, in use intravenously for over 100 years, is not "normal" and may not be the best fluid to use, especially in patients who are susceptible to renal dysfunction.
In an email to Reuters Health, lead author Dr. Dileep N. Lobo of the University of Nottingham said, "Had normal saline been formulated in recent times, it is debatable whether it would have survived a phase 1 trial."
Dr. Lobo's group carried out a randomized, double-blind cross-over trial involving 12 healthy male volunteers who were given two-liter infusions over one hour of either "normal" 0.9% saline or the balanced salt solution Plasma Lyte-148, several days apart. Plasma Lyte-148 contains sodium and chloride in physiologic amounts, compared to the higher amounts of those two ions found in normal saline.
During the four hours following the infusions, subjects underwent sequential blood and urine tests as well as magnetic resonance imaging (MRI) of their kidneys.
The main results: when the men received normal saline, they retained significantly more fluid in the extravascular space (1,484 vs 1,155 mL; p=0.031) and gained more weight (1.2 vs 0.84 kg, p=0.22). With the balanced solution, they produced significantly higher urine volumes and had a significantly shorter time to first voiding.
Furthermore, in the normal saline trials, serum chloride was significantly higher from the first hour on (p=0.0001), and a low strong ion difference indicated acidemia (p=0.025).
MRI showed that normal saline significantly decreased renal artery flow velocity (p=0.045) and renal cortical tissue perfusion (p=0.008) compared to the balanced solution - differences that could matter in patients with kidney disease.
The authors point out that some 200 million liters of normal saline are used in the U.S. every year. The paper doesn't address the issue of costs, but Dr. Lobo said, "Plasma-Lyte 148 is more expensive but this is likely to be because it is not widely used. Just because a product is more expensive does not mean that it should not be used in the clinical setting."
Dr. Lobo pointed out that a paper this year by Shaw et al, also in Annals of Surgery, showed that complications and resource use are less with Plasma-Lyte than with 0.9% saline.
Another inexpensive option, lactated Ringer's solution, has nearly normal amounts of sodium and chloride. Dr. Lobo said, "It is likely that similar results could be achieved with Ringer's lactate, however, we chose Plasma-Lyte 148 as it has a chloride content in the normal physiological range."
Dr. Laurence Weinberg of the Department of Anesthesia, Austin Hospital and Senior Fellow, Department of Surgery, University of Melbourne was not a contributor to the study. Regarding lactated Ringer's, he said, "It contains lactate. In shock conditions if lactate cannot be metabolized by the liver, it will be unable to be converted to bicarbonate. This can also result in elevated lactate levels which, if being used as a marker of effective resuscitation, can lead to misinterpretation of the cause of the hyperlactatemia."
According to Dr. Lobo, "It is clear that many patients continue to receive large quantities of intravenous fluid especially in the perioperative period. We suggest that large quantities of saline may not be beneficial for those with pre-existing renal disease or those at risk of developing renal impairment."
Dr. Lobo thinks that normal saline is not appropriate for use for resuscitation or in the operating room. He said, "There is an increasing body of evidence to suggest that saline may lead to harmful effects. This study, building on evidence first obtained in animal studies, suggests that hyperchloremia associated with saline infusion may have an unfavorable effect on renal perfusion."
Dr. Weinberg said, "For many operations we only use 1000 mL of fluid. Choice of fluid for these cases is less important. However there is now overwhelming evidence that a balanced solution is better than an unbalanced and given that the costs of normal saline and Ringer's lactate are the same I would advocate Ringer's lactate as a preference."
When massive amounts of fluid are needed, however, Dr. Weinberg would advocate Plasma-Lyte 148 over both normal saline and lactated Ringer's solution. He added, "Many critically ill patients do require significant fluid/volume intervention as part of their care; the type and correct amount of fluid patients receive is paramount. The study by Lobo now gives us information that is clinically important, and I am certain that we will see many more studies examining the clinical effects of different fluid solutions."
Dr. Lobo and one other member of his group have received financial support from Baxter Healthcare, maker of Plasma-Lyte 148. Baxter Healthcare also supported the study but did not participate in its conduct or analysis.
Dr. Weinberg's department has received funding from Baxter Healthcare, which has no input or oversight of its research.


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