SAN ANTONIO, TEX—Interest in using hypertonic fluids for sepsis and shock is being renewed because evidence is accumulating that it improves hemodynamics and the immunologic response. Although recent studies are promising, firm recommendations cannot yet be made, suggest two experts who spoke at the annual meeting of the Society of Critical Care Medicine. David B. Hoyt, MD, addressed the use of hypertonic fluids in hemorrhagic shock, and Jean-Louis Vincent, MD, discussed their role in sepsis and septic shock.[1]

“It’s too early to use hypertonic saline for treatment at the present time,” asserted Dr. Vincent, Head of the Department of Intensive Care at the Erasme University Hospital in Brussels. “However, preclinical studies are very interesting, and it is highly possible that we will use it in the future,” he continued.

In animal models, hypertonic fluids have shown a number of benefits; they improve microvascular flow, correct hemodynamic parameters, reduce organ dysfunction, modulate the immune response, and control brain edema and intracranial pressure. Hypertonic fluids also quickly raise blood pressure and increase blood flow to the organs. “Whether this will translate into clinical value remains to be seen,” said Dr. Hoyt, Professor and Vice Chairman of Surgery at the University of California, San Diego.

HEMORRHAGIC SHOCK

Dr. Hoyt and his colleagues first became intrigued with hypertonic fluids when their laboratory experiments revealed that extracellular sodium from these fluids influenced T-cell blastogenesis. Hypertonic fluids have also shown the ability to reduce levels of inflammatory mediators, such as interleukin 4 (IL-4), prostaglandin E, and transforming growth factor ß in human trauma patients.

The few hypertonic fluid trials that involved humans with hemorrhagic shock produced some positive findings. One multicenter analysis of 422 trauma patients saw a drop in the complication rate after the administration of 7.5% hypertonic saline with dextran.[2] Although no overall effect on mortality was found, subgroup analysis revealed that survival was increased among the patients given hypertonic fluids who later underwent surgery.

Another multicenter trial of hypotensive trauma patients demonstrated that 7.5% hypertonic saline with dextran produced greater improvement in blood pressure than did lactated Ringer’s solution.[3] Again, no overall difference in mortality was seen, but subgroup analysis suggested that hypertonic fluids increased survival in patients with a Glasgow Coma Scale score below 9.

Perhaps the most definitive data on hypertonic fluid therapy for hemorrhagic shock came from a 1997 meta-analysis of 14 randomized trials that included a combined population of more than 1,200 patients.[4] Eight of these studies used 7.5% hypertonic saline with 6% dextran, and six employed 7.5% hypertonic saline alone; in all trials, control patients received isotonic crystalloid.

Hypertonic saline alone did not improve survival, but in seven of the eight trials that used both hypertonic saline and dextran, the combination was associated with a mean 20% improvement in survival. The investigators concluded that hypertonic saline is no better than standard care—but hypertonic saline with dextran may be superior.

However, none of the studies included in the meta-analysis considered the immunomodulatory properties of hypertonic fluids, particularly their ability to affect intercellular signaling, said Dr. Hoyt. He believes that more research should be conducted to see if these properties can be harnessed to benefit specific groups of patients.

SEPTIC SHOCK

“In sepsis, improved blood flow from hypertonic saline helps the gut,” said Dr. Vincent. Preclinical data point to an increase in splanchnic blood flow and thus an increase in mucosal perfusion; this helps decrease bacterial translocation. In fact, there appear to be microcirculatory improvements on many levels: The decrease in endothelial swelling leads to easier passage of cells into microcirculation and a reduction of leukocyte adhesion, edema, and postischemic microcapillary reflow.

Hypertonic saline acts as an anti-inflammatory agent when given to animals with sepsis or septic shock. A drop in tumor necrosis factor and a rise in the anti-inflammatory mediator IL-10 characterize that effect. Limiting inflammation also helps preserve capillary integrity. One question that arises from these findings is whether hypertonic saline would suppress immune function entirely. This does not appear to be the case; animal models of both sepsis and trauma point to a preservation in T-cell function.

Other animal studies have shown that hypertonic saline may reduce lung membrane permeability and markers of neurologic injury. They may also restore oxygen transport and tissue oxygen consumption, improve myocardial and T-cell function, and increase survival.

Hypertonic fluids are not without risk, though. They may promote hemorrhage or a host of other adverse events, such as hyperkalemia, hyperchloremic acidosis, transient hypotension (from the solution’s vasodilating effects), arrhythmias, or coagulation disorders. Extravasation of hypertonic fluids can cause tissue necrosis; anaphylaxis is a risk if the fluids are combined with a colloid.

Clinical data for the use of hypertonic fluids in sepsis and septic shock are extremely scarce. A few small studies exist of patients with endotoxic shock. One showed that hypertonic saline improved cardiac output and blood pressure. Clearly, Dr. Vincent added, this is an area that should be watched and warrants larger examination.

—Timothy Begany

References
1. Bennett-Guerrero E, Kellum J, Vincent JL, et al. Resuscitation: fluid therapy. Presented at: annual meeting of Society of Critical Care Medicine; January 31, 2003; San Antonio, Tex.
2. Mattox KL, Maningas PA, Moore EE, et al. Prehospital hypertonic saline/dextran infusion for post-traumatic hypotension. The U.S.A. Multicenter Trial. Ann Surg. 1991;213:482-491.
3. Vassar MJ, Fischer RP, O’Brien PE, et al. A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride: the effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients. Arch Surg. 1993;128:1003-1011.
4. Wade CE, Kramer GC, Grady JJ, et al. Efficacy of hypertonic 7.5% saline and 6% dextran-70 in treating trauma: a meta-analysis of controlled clinical studies. Surgery. 1997;122:609-616.

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