STOWE, VT.—Aggressive therapy upon presentation can improve the mortality and morbidity associated with septic shock, according to Stephen Leffler, M.D.
Early appropriate antibiotics, rapid fluid resuscitation, and timely use of vasopressors can improve outcome substantially, Dr. Leffler said in a presentation on sepsis management at an emergency medicine update sponsored by the University of Vermont. Options for the most critical patients also include blood transfusions, intubation/paralysis, activated protein C, and corticosteroids.
Standard emergency department therapy for patients presenting in septic shock typically includes hemodynamic support and appropriate antibiotics, with more targeted aggressive therapy being delayed until the patient is transferred to the intensive care unit, said Dr. Leffler of the university. Recent evidence suggests that holding off on the most aggressive therapy may result in early tissue hypoxia and irreversible tissue damage, while implementing standard ICU management techniques in the ED increases the likelihood of interrupting the destructive cascade.
An investigation of early goal-directed therapy (EGT) at Henry Ford Hospital in Detroit showed that using central venous oxygen saturation (ScvO2) and pressure, measured continuously by central venous cannulation, to balance systemic oxygen delivery and consumption during the first 6 hours after presentation can significantly reduce mortality in patients with septic shock.
In the 2002 study, 236 emergency department patients with septic shock were randomized to receive either usual care or the EGT protocol. All of the patients received arterial and venous catheters. The patients in the control group were transferred to the ICU and treated according to clinician discretion. The patients who were randomized to EGT received a central line for measurement of ScvO2 and were managed in the emergency department for 6 hours before being transported to the ICU.
The EGT protocol included providing a 500-mL bolus of fluid every 30 minutes as needed to maintain central venous pressure between 8 and 12 mm Hg, administering vasopressors in the presence of mean arterial pressures less than 65 mm Hg, and giving blood transfusions to keep hematocrit levels greater than 30% if ScvO2 was below 70%. After transfusion, if ScvO2 persisted at less than 70%, the patients received dobutamine and in some cases were intubated and paralyzed to decrease oxygen consumption.
Patients in the intervention group had a 30% hospital mortality, compared with 46% for those receiving standard therapy. “The EGT group also had improved lactate, pH, and ScvO2 levels,” Dr. Leffler said.
“There are some important take-home messages in these findings, even if we're not going to get central venous oxygen saturation in every patient,” Dr. Leffler said. For example, patients in the EGT group received 5 L of fluid in the first 6 hours of treatment—1.5 L more than the standard therapy group. “This tells us that we are probably underhydrating these patients, and that we should be more aggressive with fluids. The standard 1,500 cc is not going to be enough,” he said.
Additionally, the blood transfusion rate was 64% for EGT patients, compared with 18% for the control group. The message in this, Dr. Leffler said, “is to go ahead and type and cross if the patient's [hematocrit] goes below 30%. A couple of units of blood might help.”
There was no difference in the rates of intubation and vasopressor use between the two groups.
While studies of similar management strategies implemented in the ICU have failed to show similar outcome improvements, “I think the critical element is the timing,” Dr. Leffler said. “The intervention in the emergency department was probably initiated earlier, before irreversible end-organ dysfunction.”
Specific subsets of patients in septic shock may also benefit from treatment with activated protein C or corticosteroids, Dr. Leffler said. “There is some evidence that treatment with [recombinant] activated protein C can reduce mortality in septic shock, but this benefit appears only in the sickest patients,” specifically those with respiratory and hemodynamic failure, who are at increased risk of death from sepsis, Dr. Leffler said.
To be effective, the drug must be administered within 24 hours of sepsis-induced failure, and it should not be considered for patients with coagulopathy because of the increased bleeding risk, he said.
The drug's high cost also is a caveat, Dr. Leffler said. “At $7,250 per dose, [activated protein C] is not yet used routinely and won't be until more evidence shows it to be far better than other options,” he contended.
Corticosteroids also have a role in sepsis management, but not the high-dose, short-course, broadly administered regimens of the 1970s that proved ineffective in later trials, he said.
Recent studies have shown that more than half of all septic patients could have a relative adrenal insufficiency that may be implicated in worse outcomes. In a study of patients with relative adrenal insufficiency—identified by a corticotrophin stimulation test on admission—those treated with steroids had lower 28-day mortality than did those randomized to receive placebo in addition to standard therapy.