Special thanks to Brian Johnston, MD MPH, Chief of Pediatrics at Harborview Medical Center for contributing this article.

The following is a composite case which combines details from more than one case to preserve confidentiality. It illustrates an issue in pediatric mortality identified by the multi-disciplinary King County Child Death Review Team:

A 3-month-old previously healthy infant was taken to a local emergency department for evaluation of fever. The child had had mild upper respiratory symptoms without cough. He had no vomiting or diarrhea. There were no ill contacts. Fever had developed 2 hours before presentation.

On examination, the child was described as irritable, but "non-toxic" in appearance. He had a temperature of 40°C, a respiratory rate of 30, and a pulse of 220. There were no focal findings on physical exam. There was no rash. His extremities were described as cool. WBC was 8,000 with no band forms. Urinalysis was remarkable only for a specific gravity of 1.030. A blood culture was obtained, and an IV placed. To address poor perfusion, the child received 40 cc/kg of isotonic fluids over a 3 hour period. His heart rate was 180 at discharge. The parents were instructed to follow-up with their primary care provider the next day.

Four hours after ED discharge the parents noted that the child's breathing was labored. He had developed a petechial rash. The parents then noted seizure-like activity during which the infant became apneic. The family initiated CPR, and called for assistance. The child died at a tertiary referral center 2 hours later. The blood culture, drawn less than 12 hours earlier in the ED, grew Neisseria meningitidis, serotype B.

This infant presented in septic shock and died from fulminant meningococcemia. Infants and children with febrile illness account for up to 20% of visits to a general Emergency Department. Most have benign, self-limited illnesses and require only supportive care and parental reassurance. The challenge remains to identify the small proportion of febrile children with invasive bacterial disease requiring aggressive therapy. Unfortunately, as this case illustrates, early signs of septic shock in infants may be subtle while the progression of the disease is rapid and dramatic.

Sepsis is a clinical diagnosis and does not rely upon isolation of a specific organism¹. Septic shock should be suspected in an infant with evidence of an infection (manifest as fever or hypothermia) who also has clinical signs of decreased perfusion, including altered mental status (irritability, lethargy, lack of interaction with parents), decreased urine output, peripheral vasodilation ("warm" shock) or vasoconstriction ("cool" shock). Hypotension is a late finding and is not required for the clinical diagnosis of septic shock.

The American College of Critical Care Medicine has developed treatment guidelines for the hemodynamic support of pediatric and neonatal septic shock². Early and aggressive fluid therapy is recommended to restore circulating volume in the first hour of therapy. Large deficits typically exist, and initial volume resuscitation may require up to 60 cc/kg over 15 minutes. Studies from community samples suggest that each hour of delay in reversing shock doubles the odds of death for the child³.

Protein-conjugate vaccines have dramatically reduced the incidence of invasive Haemophilus influenzae type b⁴ and, more recently, Streptococcus pneumoniae among infants and young children⁵. With these diseases on the wane, practitioners may be tempted to abandon previously published guidelines that called for careful laboratory evaluation and empiric treatment of febrile infants. Nevertheless, serious bacterial disease remains a concern in this age group and a high level of clinical suspicion is warranted. Organisms still capable of causing invasive disease in infants include: Haemophilus influenzae type b or pneumococcus in the un-immunized, partially immunized or fully immunized child (due to vaccine failure); non-type b H. flu strains, pneumococcal strains not covered by the heptavalent conjugate vaccine; late-presenting group B streptococci; Neisseria meningitidis; Salmonella species; and other Gram-negative enteric bacilli. Risk factors for occult bacterial infection in the febrile infant include toxic appearance, altered mental status, higher fever, and younger age.

Although still an uncommon disease, invasive menin-gococcal infection is has its highest incidence among infants⁶ and early recognition and treatment remains the mainstay of control⁷. Opportunities to prevent disease through vaccination in infancy are limited because more than half of cases among those less than 1 year of age are caused by serogroup B, for which no vaccine is licensed or available in the United States. For other serotypes, the currently available meningococcal polysaccharide vaccines provide limited efficacy of short duration in young children⁷. Protein conjugate serogroup C meningococcal immunization was recently introduced in the United Kingdom and may augment our ability to control a proportion of meningococcal disease among children when this vaccine becomes available in the United States⁸.