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Early IV Fluids Crucial in Battling E. Coli

Of the approximately 1,000 children who suffer from E. coli O157:H7 infections each year, 15 to 20 percent develop the life-threatening kidney disease HUS — hemolytic uremic syndrome. But an important new study indicates that patients who receive fluids intravenously early in the course of the illness are less likely to develop this serious complication.

Researchers at Washington University in St. Louis (WUSL) medical center analyzed the cases of 50 patients under the age of 18 who were treated for HUS at 12 pediatric hospitals in the U.S. and Scotland. They found that 68 percent became unable to urinate, a catastrophic step in the disease’s progression.

However, of the 25 patients who received no IV fluids within 4 days of getting sick, 84 percent stopped urinating. Of the other 25 patients who did get IV fluids right away, only 52 percent stopped urinating.  Other factors did not seem to make a difference.

“If kids were given any IV fluids in the first 4 days of illness, they were more likely to continue peeing and have decreased complications. They were less likely to need to go on dialysis. Their hospitalization courses were shorter. They just did better,” said Christina Hickey, a third year resident at WUSL Children’s Hospital and lead author of the study.

HUS develops when the harmful Shiga toxins produced by E. coli O157:H7 bacteria destroy the tissue of small blood vessels, which clog and damage red blood cells that cannot squeeze through the obstructed passages. The kidney, which needs adequate bloodflow to filter out waste, becomes compromised and the patient can no longer secrete urine.

HUS is the most common cause of acute kidney failure in infants and young children, and more than half the children with HUS require dialysis. But as the recent E. coli outbreak in Europe has demonstrated, adults infected by pathogenic E. coli are also susceptible to HUS.

Hickey says the increased blood flow provided by sodium-containing, intravenous fluid, which expands blood vessels, could decrease the odds for oliguria, or low urine output. Oral fluids aren’t effective, because E. coli patients are experiencing such profuse bouts of diarrhea, and may also be vomiting, that they can’t remain hydrated on their own.

In a story by the Washington University in St. Louis Newsroom, Hickey explained: “HUS is like a heart attack to the kidneys. What we’re trying to do is make sure the kidneys get enough blood flow. By giving intravenous fluids, we try to keep those kidneys working and to keep these children urinating. We think this will have a substantial impact on reducing the severity of kidney failure in these kids.”

The study showed that the ability of the young patients’ kidneys to fend off the negative effects of the disease directly correlated to the amount of IV fluids the children had received.

Preventing the development of HUS is crucial in the course of an E. coli infection, because there is no way to treat the kidney disease once it occurs, and no way to lessen the severity of kidney injury it causes. According to the study, administering IV fluids immediately after the onset of bloody diarrhea, a common symptom of an E. coli O157:H7 infection, could reduce a child’s chances of developing an illness that becomes a wait-and-see game once it has taken hold.

Hickey says children with bloody diarrhea should be examined immediately by a health-care provider. There is a narrow window of opportunity in which IV fluids must be administered before it’s too late.

“If a child is identified early as having an E. coli O157:H7 infection, we think that intravenous fluids can help protect the kidney and possibly help that child avoid dialysis,” says Hickey. “The important thing is for providers to identify the kids at risk for E. coli O157:H7 infection early,” says Hickey.

The study authors point out that early diagnosis is sometimes difficult because doctors must wait for the results of microbiological tests of stool specimens to confirm whether a patient has E. coli. More rapid testing is needed, the authors note, in order to avoid this delay.

They also urge doctors to recognize the signs of an E. coli infection and take swift measures to diagnose a patient.

“We considered the possibility that providers hesitated to give fluids to children who were on the verge of developing HUS,” the study says. “However, half or fewer of the children in this cohort underwent any testing, received any intravenous fluids, or were admitted to any hospital in the first 4 days of illness, well before HUS is diagnosed. Such inaction does not reflect major provider concerns about impending renal failure at the initial encounter.”

This research builds on the findings of a previous study, which also showed that administering IV fluids can curb the downward spiral leading to kidney failure in E. coli O157:H7 infected patients. However, that study was confined to 29 patients under the age of 10 in Seattle, while this one examined children of all ages in hospitals in St. Louis; Seattle; Sacramento; Albuquerque; Little Rock; Milwaukee; Cincinnati; Indianapolis; Memphis; Columbus, Ohio; and Glasgow, Scotland.

Given the findings of this research, the authors note with dismay that giving IV fluids to E. coli patients is not already standard procedure.

“It is concerning that 14 of the 39 subjects who were evaluated during the first 4 days of illness received no intravenous fluids, and of those who did, few received the volume or sodium content we have recommended,” the study says. “Opportunities to provide volume expansion in that critical interval appear, therefore, to have been lost.”

The team’s findings were released last week, as doctors in Europe continued to treat patients of the recent outbreak of E. coli O104:H4 there, where as many as 900 of the almost 4,000 outbreak victims developed HUS.

This study was released ahead of its scheduled publication time in hopes that it might provide guidance to the European community. That epidemic was caused by a different strain of E. coli than the one examined in this paper, but has similar effects.

“Because of the important public health implications of this study, we have decided to publish this article quickly online ahead of print,” says a note from the editor.

Hickey’s St. Louis collaborators were Dr. Robert J. Rothbaum, the Centennial Professor of Pediatrics, and Dr. Anne M. Beck, associate professor of pediatrics, both at Washington University School of Medicine. Dr. Phillip I. Tarr, the Melvin E. Carnahan Professor of Pediatrics and director of the Division of Pediatric Gastroenterology, supervised Hickey on the study and is senior author of the paper.

The study, “Early Volume Expansion during Diarrhea and Relative Nephroprotection During Subsequent Hemolytic Uremic Syndrome,” was published July 22, 2011, in Archives of Pediatric and Adolescent Medicine.

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