Increased incidence of sepsis and altered monocyte functions in severely injured type A - glucose-6-phosphate dehydrogenase-deficient African American trauma patients

Objective: To determine whether trauma patients with the common, type A- gl ucose-6-phosphate dehydrogenase (G6PD) deficiency have an aggravated inflam matory response, increased incidence of septic complications, and/or more p rofound alterations in leukocyte functions compared with nondeficient traum a patients. Settings: Intensive and surgical care units of a trauma center and flow cyt ometry and experimental laboratories at a teaching university hospital. Design:Prospective cohort clinical study with measurements on days 2 and 5 postinjury. Monocyte and neutrophil oxidant content, apoptosis, and CD11b e xpression and plasma cytokine levels were compared between G6PD-deficient a nd nondeficient patients. Patients: A total of 467 male African American trauma patients were screene d for the deficiency. Forty-four type A-(202/376) G6PD-deficient patients w ere identified and enrolled in the study; 43 nondeficient patients were als o enrolled and were matched by age, clinical criteria of injury severity, a nd type of trauma. Main Results:After severe injury (Injury Severity Score, greater than or eq ual to 16), 50% of the deficient and 6.2% of nondeficient patients develope d sepsis with positive bacterial blood cultures. In deficient patients, the frequency of bronchial (75%) and wound infections (25%) was also increased compared with nondeficient patients (32% and 0%). The durations of systemi c inflammatory response syndrome, Sepsis Syndrome, and days on antibiotics were three times longer in deficient than in nondeficient individuals. Howe ver, adult respiratory distress syndrome occurred in 37% of both groups. An emia was more severe in the deficient than nondeficient patients from day 1 0 posttrauma. On day 5, the peroxide content was doubled, apoptosis was dec reased, and CD11b expression was increased in monocytes from deficient pati ents compared with cells from nondeficient patients. On day 5, the plasma i nterleukin (IL)-10 concentration was significantly lower in deficient than nondeficient patients, whereas tumor necrosis factor-ru, IL-6, and IL-8 lev els were similar. After moderate injuries (Injury Severity Score, 9-16), th e deficiency was not associated with adverse clinical effects, and the trau ma-induced changes in leukocyte function were similar in deficient and nond eficient patients. Conclusions:The common type A- G6PD deficiency predisposes septic complicat ions and anemia in trauma patients after severe injuries as defined by an I njury Severity Score of greater than or equal to 16. This adverse clinical course is accompanied by altered monocyte functions manifested as augmented oxidative stress, a decreased apoptotic response, increased cell adhesion properties, and a diminished IL-10 response.