Risk of Sepsis Death Soars With Antibiotic Delays


PHOENIX, ARIZ. — Risk of death from sepsis increases by 6%-10% with every hour that passes from the onset of septic shock until the start of effective antimicrobial therapy, according to a review of more than 2,600 consecutive cases at 15 intensive care units in five U.S. and Canadian cities.

“You already have a substantially increased risk of death if you get antibiotics by the second hour after onset of hypotension compared with the first hour—and that odds ratio continues to climb out to 36 hours,” principal investigator Anand Kumar, M.D., said at a meeting sponsored by the Society of Critical Care Medicine.

Relatively few patients received appropriate antibiotics within 2 hours, however.

Dr. Kumar, head of the emergency department at the University of Manitoba in Winnipeg, reported that at every hospital studied, “Only half of septic shock patients received an antibiotic within 6 hours of onset of recurrent or persistent hypotension.”

Early administration of appropriate antibiotics is crucial because it eliminates the source of sepsis, according to Dr. Kumar. “You can keep the patients alive for days, but if you don't eliminate the source in the first couple of hours, they are not going to make it,” he said.

All told, 43.8% of 2,731 septic shock patients reviewed by Dr. Kumar and his colleagues survived to hospital discharge. Removing patients who were moribund at presentation (those who required intubation or cardiopulmonary resuscitation in the field) reduced the population to 2,675 patients, but barely nudged the survival rate up to 44.7%.

The population had slightly more men than women and an average age of 62.5 years. Nearly half the patients, 43%, came from emergency departments. Another 28% had been in medical wards, and 18% on surgical floors.

Nosocomial infections accounted for 42% of cases. Malignancy was the most common comorbidity (20%), followed by chemotherapy and elective surgery, each about 15%. The average Acute Physiology and Chronic Health Evaluation II score was 25.9.

Dr. Kumar said emergency departments were about an hour faster than other areas of the hospital in delivering antibiotics, but still too slow. The median emergency department time to treat was 4.5-5 hours, he said.

The investigation started with animal studies. In those experiments, mortality was held to 10% if the animals were given an antibiotic within a 12-hour window before the onset of hypotension, according to Dr. Kumar. The mortality became 80% if the antibiotic was started 15 hours afterward, and 100% at 24 hours.

In the human retrospective study reported at the meeting, 89% of patients who received an appropriate antibiotic within the first half hour survived, he said. By the second hour, the survival rate dropped to 84%, and it continued to drop at a rate of 7.5% every hour thereafter.

Subset analyses by numerous factors mostly produced P values of .0001 without changing the risk, according to Dr. Kumar. Patients who were obviously sicker at presentation received antibiotics faster, improving their odds of surviving, he said.

Only about 50 patients, all in the United States, had methicillin-resistant Staphylococcus aureus, which was not seen in Winnipeg, according to Dr. Kumar.

He noted that the investigators focused on time to effective antibiotics. If the first choice is not effective, the effects of any initial delay can be all the more overwhelming, he said.

Dr. Kumar called for hospitals to use medical response teams with algorithm protocols for patients in septic shock. He reported that his hospital has instituted the following changes in response to the study:

▸ Staff can start intravenous antibiotics in hypotensive sepsis patients without waiting for approval.

▸ Nurses have been told that the first dose of any new antibiotic is an automatic stat order.

▸ No sepsis patient is transferred to an intensive care unit without receiving an antibiotic before leaving the emergency department.

Many emergency physicians do not realize that an antibiotic order may wait for hours if it is not marked “stat,” according to Dr. Kumar. If the patient is transferred to an ICU, more hours might pass before the antibiotic is delivered with scheduled medications, he warned.

“These simple administrative changes can reduce time to antibiotics by 2 hours,” he said. “And, if these data hold, that's a translation to a 15% absolute improvement in mortality.”

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