Standard Septic Shock Treatments Ineffective
WEDNESDAY Jan. 9, 2008 -- Two new studies on the treatment of septic shock question the conventional wisdom of treating with corticosteroids, intensive insulin therapy or with the synthetic fluid replacement substance called pentastarch.
The first study compared the use of hydrocortisone to a placebo in people in septic shock and found no improvement in survival rates.
The second study looked at the use of intensive insulin therapy versus a placebo, and the use of pentastarch to the more commonly used Ringer's lactate, which is saline with added lactate, chloride, potassium and calcium. Both intensive insulin and pentastarch failed to improve survival rates, and, in fact, increased the rates of serious complications so much that the trial was stopped early.
Results of both studies are published in the Jan. 10 issue of the New England Journal of Medicine.
Septic shock is "associated with significant morbidity and mortality. Standard treatment for septic shock includes antibiotics, intravenous fluids and vasopressor medicines (drugs to increase blood pressure)," explained the first study's lead author, Dr. Charles Sprung, director of the general intensive care unit, department of anesthesiology and critical care medicine at Hadassah Hebrew University Medical Center in Israel. "Until our study, doctors in hospitals around the world were also routinely using steroids as adjunct therapy to help hundreds of thousands of patients in septic shock fight for their lives. Our study demonstrates that this adjunct therapy of hydrocortisone is not helpful for most patients with septic shock and, in fact, may be harmful."
Septic shock occurs when an infection, usually bacterial, overwhelms the body's natural defenses, according to the U.S. National Institutes of Health. The major symptoms include low blood pressure and low blood flow. If not effectively treated, failure of the kidneys, liver, brain and heart may occur. Septic shock is a life-threatening condition.
The original theory behind using steroid medications to treat septic shock was that doctors hoped it would reduce the inflammation that accompanies septic shock, according to Sprung. However, along with anti-inflammatory action, steroids can also suppress the immune system, which may be detrimental for someone fighting an infection.
Dr. Louis Saravolatz, an infectious disease specialist and chairman of the department of medicine at St. John Hospital and Medical Center in Detroit, also pointed out that it's possible the inflammation seen with septic shock may be part of the body's natural defense, and "maybe it's helping us fight infection."
In any case, the use of corticosteroids in septic shock has remained controversial for decades, and numerous studies have been conducted, often with conflicting results. To try to definitively assess whether or not steroids could provide benefit, Sprung and his colleagues randomly assigned almost 500 people in septic shock to receive either 50 milligrams of hydrocortisone intravenously every six hours for five days, or a placebo. The researchers found no statistically significant differences in survival between the groups. The incidence of septic shock was reversed more quickly in the corticosteroid group, but this benefit was offset by additional episodes of "super-infection" with new sepsis and septic shock.
"If it takes 30 years of study [to find a benefit], it probably isn't having a whole lot of effect," Saravolatz noted.
The second study, which was stopped early for safety reasons, sought to compare other commonly used septic shock treatments to assess their efficacy.
German researchers recruited 537 people in septic shock and randomly assigned them to receive either intensive insulin therapy or standard insulin therapy or a modified Ringer's lactate solution versus a pentastarch solution. Pentastarch is a synthetic fluid replacement substance.
The idea behind intensive insulin therapy originally came from a study of cardiac surgical patients that found when blood sugar was kept in the normal, healthy range, mortality was reduced, according to Saravolatz. "The immune system doesn't work well if blood sugar is too high," he explained.
In this study, however, the German researchers found that intensive insulin therapy didn't produce a statistically significant reduction in death rates but did increase the risk of serious adverse events, such as critically low blood sugar (hypoglycemia). In the intensive insulin group, 17 percent had severe hypoglycemia compared to just 4 percent of those on standard insulin therapy.
Additionally, the researchers found that pentastarch was associated with higher rates of kidney failure than Ringer's lactate.
"The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia," said one of the study's lead authors, Dr. Frank Brunkhorst, a senior physician in internal and intensive care medicine at the Clinic for Anesthesiology and Intensive Care at Friedrich Schiller University of Jena in Germany.
And, he added, "As used in this study, [pentastarch] was harmful, and its toxicity increased with accumulating doses."
Saravolatz said: "This is a fascinating study that has the potential to really change what we're doing. This study will relieve some of the intense efforts to get blood sugar lower. I'm not saying we'll let people have blood sugars of 200 or 300, but this study will have an impact.
"And, this study shows that pentastarch really is potentially harmful," he said, adding that for most patients with septic shock, "salt water (saline) and the right antibiotics are probably all we need."
To learn more about septic shock, visit the U.S. National Library of Medicine.
Posted: January 2008
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