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Antioxidants May Increase Sepsis Survival
Animal-Model Results Promising

(DES PLAINES, Ill., March 30, 2004) - Combining antioxidants with the standard sepsis treatments of antibiotics and fluid resuscitation can increase sepsis survival in an animal model, according to an article in the February issue of Critical Care Medicine.

"Our study suggests that antioxidants could be of great value in the clinical practice of critical care," said senior author Felipe Dal-Pizzol, M.D., Ph.D., from the Laboratório de Fisiopatologia Experimental at the Universidade do Extremo Sul Catarinense in Criciúma, Brazil.

The researchers have completed animal studies and are now initiating a human clinical trial to evaluate the antioxidants N-acetylcysteine (NAL) and deferoxamine (DFX), which showed promise in this study.

"Hopefully human trials will show that this relatively safe and low cost antioxidant therapy reduces sepsis mortality when used in conjunction with standard sepsis treatment," said Dr. Dal-Pizzol. "The relatively few alternative sepsis treatments that are available are generally costly and limited to certain subgroups of patients. We expect that the combination of NAL plus DFX could be used in a wide spectrum of patients."

The researchers infected 50 rats with sepsis and divided them into five groups to evaluate the effects of NAL plus DFX in a sepsis animal model. The five treatments consisted of the following: 1) no treatment 2) NAL plus DFX 3) fluids 4) NAL, DFX and fluids 5) fluids and antibiotics.

The researchers found that 10 percent of untreated septic rats survived, 40 percent survived with fluids and antibiotics, 47 percent of survived with NAL and DFR, while survival increased to 66 percent in rats given NAL and DFR plus fluids and antibiotics.

"Although antioxidants may not be the 'magic bullet' of sepsis treatment, they may add to the efficacy of current therapies," said Dr. Dal-Pizzol. "According to our animal efficacy study, antioxidants may block several detrimental processes that occur during sepsis. Antioxidants are not yet recommended in clinical practice, but my hope is that antioxidants will soon improve human sepsis mortality.

Septic shock is a major cause of morbidity and mortality in critical care patients. Reactive oxygen species has been demonstrated to play a role in the development of multiple organ failure and septic shock.

Elevated circulating nitric oxide has been reported in septic patients. The researchers previously found that an imbalance between superoxide dismutase and catalase activities during sepsis response could predispose the accumulation of hydrogen peroxide. This environment predisposes the formation of peroxynitrite and hydroxyl radicals that are thought to be the most dangerous nitrogen and oxygen derivatives in biological systems.

NAL and DFR are currently used in the clinical practice. "Both medications have a favorable profile that encourage us to start a clinical trial in sepsis," Dr. Dal-Pizzol said.

"We do not expect that antioxidant therapy alone will greatly improve the survival of patients with sepsis, because sepsis cannot be simply reduced to a free-radical pathology. We consider antioxidants to be useful components of multidrug therapies," concluded the authors. "We believe that the approach described here is a more rational alternative to the use of antioxidants in sepsis treatment since they can blockade free radical generation in several different steps."

"Now that other animal models in acute respiratory distress syndrome and hepatic failure are bolstering our study findings, we are interested in the effects of antioxidants in mitochondrial function during sepsis and the effects of the antioxidants in humans with sepsis," Dr. Dal-Pizzol said.

Critical Care Medicine is the official journal of the Society of Critical Care Medicine. It is the premier peer-reviewed, scientific publication in critical care medicine. Each issue presents critical care practitioners with clinical breakthroughs that lead to better patient care, the latest news on promising research, and advances in equipment and techniques.

EDITOR'S NOTE: This research is supported by governmental Brazilian agencies of research support (CNPq, FAPERGS) and was performed in collaboration to Dr José Cláudio Fonseca Moreira and colleagues.

For more information, contact Thomas Joseph, MPS, CAE at (847) 827-7282 or tjoseph@sccm.org.

The Society of Critical Care Medicine is the leading professional organization dedicated to ensuring excellence and consistency in the practice of critical care medicine. With over 11,000 members worldwide, the Society is the only professional organization devoted exclusively to the advancement of multidisciplinary, multiprofessional intensive care through excellence in patient care, professional education, public education, research and advocacy. Members of the Society include intensivists, critical care nurses, critical care pharmacists, clinical pharmacologists, respiratory care practitioners and other professionals with an interest in critical care, which may include physician assistants, social workers, dieticians, and members of the clergy.

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