The purpose of this study is to evaluate the pharmacokinetics of pioglitazone and to determine the effect on inflammatory biomarkers for pioglitazone in patients with severe sepsis and septic shock.

Severe sepsis is a major cause of morbidity and mortality among adults and children. Few clinical trials have demonstrated clinical benefit in sepsis. Severe sepsis is a systemic inflammatory syndrome in response to infection that is associated with acute organ dysfunction. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARg) is involved in the regulation of the sepsis-induced inflammatory response. The central hypothesis is that pioglitazone reduces the inflammatory responses in children with severe sepsis and septic shock.

Inclusion Criteria:

• Weight range between 30 to less than or equal to 90kg
• Have a known or suspected infection and meet criteria for severe sepsis or septic shock as defined according to the International Pediatric Sepsis Consensus Conference guidelines

Exclusion Criteria:

• Are in a moribund state in which death is perceived as imminent
• Have an advanced directive or do not resuscitate order to withhold life-sustaining
• Have a history of cyanotic heart disease or congestive heart failure
• Have a serum transaminase level (ALT) that exceeds about 2.5 times the upper limit of normal (>112 unit/L)
• Are or become pregnant
• Are already on or have a history of taking pioglitazone or rosiglitazone
• Have type 1 or 2 diabetes
• Have total body weight below 30 kg or above 90 kg
• Have a serious condition, in addition to sepsis, which in the opinion of the investigator would compromise the participant

Adverse events were monitored for each subject throughout each subject's hospitalization which ranged from 4 days to 30 days for control subjects and 4 days to 23 days for pioglitazone subjects.

Small sample size