Making sense of septic shock

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Timing is everything when it comes to patient survival.

Recognition of septic shock has been increasing, thanks to developments in the understanding of its pathophysiology, new treatment modalities, and revised international treatment guidelines with the stated aim of lowering the mortality rate.

But more attention is needed, say some critical care doctors, because when it comes to patient survival, timing is everything.

Septic shock accounts for many of the deaths in medical and surgical critical care. Worldwide, sepsis is increasingly common and treatment consumes a large amount of healthcare resources.

And in an editorial in the Feb. 28 issue of the New England Journal of Medicine, Dr. Joseph Parrillo, Chief of the Department of Medicine at Cooper University Hospital in Camden, N.J., and Professor of Medicine at Robert Wood Johnson Medical School, calls septic shock, "one of the most challenging problems in critical care."

But despite its prevalence and severity, septic shock isn't nearly as well recognized as other emergencies, including trauma, heart attack, and cardiogenic shock, Parrillo told Healthcare Middle East, adding that often clinicians don't treat it with the same sense of "urgency" as other emergencies.

Unfortunately, this delay can have tragic consequences. In this In Practice, Parrillo explains why early intervention is so important, and discusses the latest thinking on antibiotic therapy, steroids, and glucose control.

Sepsis is a complex medical condition that begins with an infection and results in an exaggerated immune response. The inflammatory response ultimately leads to organ damage and eventually multiple organ failure.

Early goal-directed therapy

Research suggests that early intervention is critical to patients' survival, Parrillo says. "When someone comes to the emergency room with septic shock, they need to be treated immediately and aggressively."

He emphasizes the importance of an approach called early goal-directed therapy, which involves treating low blood pressure with aggressive fluid resuscitation and maintaining it with vasopressors. Beginning antibiotic therapy within the first hour is important as well.

Initiating such therapies as close as possible to the onset of septic shock is invaluable, says Parrillo, noting that several studies confirm the relationship between timing and mortality.

For example, a randomized controlled trial published in the Nov. 8 2001 issue of the New England Journal of Medicine, showed that giving early cardiovascular support (using a defined protocol of fluids, vasopressors, dobutamine, and blood transfusions) reduced mortality from more than 45 percent to around 30 percent.

Another large observational study, published in 2006 in Critical Care Medicine, showed that giving patients with septic shock antibiotics within the first hour of onset resulted in a 20% mortality rate, whereas giving that treatment six hours later nearly tripled that mortality rate.

These studies point to what Parrillo calls a "golden hour" for applying therapy to patients with septic shock. This thinking is reflected in updated international guidelines published in the January issue of the journal Critical Care Medicine.

The guidelines strongly recommend that fluid resuscitation begin immediately in patients with hypotension (no change from the 2004 guideline), and therapy with broad-spectrum antibiotics begin within the first hour of recognizing severe sepsis and septic shock (a more strongly worded recommendation than the previous guideline contained).

Vasopressors

The current "Surviving Sepsis" guidelines not only recommend vasopressors to treat hypotension in patients with septic shock but recommend particular agents, norepinephrine or dopamine. Over the years, some investigators have looked at the value of substituting vasopressin for norepinephrine.

But the authors of a recent randomized controlled trial of 779 patients (the VASST Trial), published in the Feb. 28, 2008 New England Journal of Medicine, found that substituting vasopressin for norepinephrine did not reduce mortality rates, and concluded that there is no value in such substitution.

Parrillo agrees with this conclusion. Although this study found that adding vasopressin to norepinephrine therapy in patients with septic shock appears to be safe, he says, "there is no advantage to using vasopressin instead of norepinephrine." But he emphasizes that the timing of vasopressor therapy is more decisive than is the choice of vasopressor agent.

Steroids

Steroids represent one of the most controversial areas in septic shock therapy. For the past three decades, investigators have been looking at the role of corticosteroids in treating septic shock.

When the body is stressed, the adrenal glands make corticosteroids to help maintain blood pressure and other homeostatic mechanisms. Studies done 30 years ago suggested that a large dose would be helpful in septic shock.

But over the past five or six years, there has been a growing consensus that it is preferable to give patients a smaller, physiologic dose (around 300 mg/day) instead.

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