Children who received no initial fluid bolus during intravenous fluid resuscitation somewhat surprisingly fared far better than those who received standard doses of saline or albumin (20 to 40 cc per kg). As reported in the June 30 New England Journal of Medicine, the Fluid Expansion as Supportive Therapy (FEAST) Trial group studied resuscitation options in East African children with severe febrile illness and impaired perfusion. (2011;364:2483.)
In an accompanying editorial, the clinician caring for the septic patient is warned that “bolus-fluid resuscitation … in patients with compensated shock who do not have a clinical fluid deficit must be practiced with much greater caution than is now the case and with increased vigilance.” (New Engl J Med 2011;364:2543) This advice surely flies in the face of current guidelines for managing septic patients, children and adults alike, so what is the emergency physician to do?
Researchers in this study, conducted in Uganda, Kenya, and Tanzania, randomly assigned 3,141 children with suspected sepsis (severe febrile illness, signs of impaired perfusion, end-organ dysfunction) to receive up to 40 cc/kg of normal saline or albumin or no fluid bolus at all. Hypotensive patients were assigned to a different protocol.
Notable exclusion criteria included gastroenteritis and noninfectious causes of shock. The study found a roughly 3.3 percent absolute difference in mortality favoring no fluid bolus in these patients at 48 hours and four weeks. For every 30 children treated with fluid boluses, there was one additional death, which is a striking number given the millions of children presenting with severe febrile illnesses in this area each year.
It is no surprise that the editorial author was moved to question the wisdom of aggressive fluid resuscitation in all septic patients based on these results, but it is not clear how much we can generalize from this study. More than half of these patients were positive for malaria parasitemia, roughly one-third were visibly jaundiced, one-third were severely anemic with hemoglobin less than 5 g/dl, and 83 percent had signs of respiratory distress. Conversely, only 12 percent had positive blood cultures.
Most patients in this study were suffering from a disease entity distinct from bacterial sepsis, and perhaps a third or more may have been in shock from severe anemia rather than infection-induced vascular and cellular dysfunction. From that point of view, it is reasonable to expect that aggressive crystalloid or colloid administration, without blood transfusion, would exacerbate anemia and its sequelae, such as heart failure and tissue hypoxia in such patients. It is important to note, that in this very resource-limited setting, these children were all treated on general pediatric wards without access to mechanical ventilation, pressors, or intensive care.
In stark contrast to the FEAST findings, guidelines for managing sepsis and septic shock call for aggressive fluid resuscitation: 60 cc/kg in children per the American College of Critical Care Medicine (Crit Care Med 2009;37:666) and at least 20 cc/kg in adults according to the Surviving Sepsis campaign (Crit Care Med 2008;36:296). As the FEAST results remind us, aggressive fluid resuscitation in some patients may be harmful, leading to pulmonary edema, cerebral edema, electrolyte disturbances, or worsening anemia (as in these patients with malarial illness).
Closer to home, children with primary CNS infections or severe pneumonia as the basis for sepsis may not tolerate fluid boluses due to high levels of antidiuretic hormone. Aggressive fluid therapy also may lead to worsening respiratory function in the short term, and it must be carried out in a setting that can initiate and maintain mechanical ventilation safely. Finally, children with diabetic ketoacidosis should be treated carefully with intravenous fluids because high volumes of IV fluid administration may be associated with higher rates of cerebral edema. The American Diabetes Association's consensus recommendation is that children in DKA, without hypotension, receive no more than 10 cc/kg of initial normal saline bolus. (Diabetes Care 2006;29:1150).
The results of the FEAST trial may be extremely relevant for developing resource-limited protocols for sick febrile children with malaria and severe anemia. These results are simply not applicable to patients in emergency departments in more economically developed countries, however. The emergency physician treating the febrile child with signs of impaired perfusion, such as sepsis, should still administer intravenous fluid up to 60 cc/kg to reverse early shock, as recommended by expert guidelines.
Along with selecting and administering appropriate antibiotics and identifying and treating end-organ dysfunction such as respiratory failure, administering IV fluids early remains at the core of the emergency physician's role in treating sepsis. Special cases where aggressive fluid administration may be harmful, such as severe anemia, DKA, and severe CNS infection, should be managed with an appropriate specialist, and emergency physicians should use additional monitoring to guide fluid management.
Dr. Lundberg is an assistant clinical professor of medicine at the David Geffen School of Medicine at the University of California at Los Angeles, the associate program director of the UCLA Emergency Medicine/Internal Medicine Residency, and the assistant medical director of emergency medicine at Olive View-UCLA Medical Center. Luis Lovato, MD, serves as the medical editor for this column. He is an associate professor at the David Geffen School of Medicine at UCLA, the director of critical care in emergency medicine at Olive View-UCLA Medical Center, the co-chair for the Emergency Medicine Best Practices Committee for the Los Angeles County Department of Health Services, and an instructor for the National MegaLLSA Review Course (www.megallsa.com).
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