Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients.
OBJECTIVE
To investigate whole body in vivo cysteine kinetics and its relationship to whole blood glutathione (GSH) synthesis rates in septic, critically ill pediatric patients and controls.


METHODS
Prospective cohort study.


METHODS
Multidisciplinary intensive care unit and pediatric inpatient units at a children's hospital.


METHODS
Ten septic pediatric patients and ten controls (children admitted to the hospital for elective surgery).


METHODS
Septic patients (age, 31 months to 17 yrs) and controls (age, 24 months to 21 yrs) received a 6-hr primed, constant, intravenous tracer infusion of l-[1-13C]cysteine. Blood samples were obtained to determine isotopic enrichment of plasma cysteine and whole blood [1-13C]cysteinyl-glutathione by gas-chromatography mass spectrometric techniques. The plasma flux and oxidation rate of cysteine and the fractional and absolute synthesis rates of GSH were determined. Septic patients received variable protein and energy intake, as per routine clinical management, and controls were studied in the early postabsorptive state.


RESULTS
Plasma cysteine fluxes were increased in the septic patients when compared with the controls (68.2 +/- 17.5 [sd] vs. 48.7 +/- 8.8 micromol x kg(-1) x hr(-1); p <.01), and the fraction of plasma cysteine flux associated with oxidative disposal was similar among the groups. The absolute rates of GSH synthesis in whole blood were decreased (p <.01) in the septic patients (368 +/- 156 vs. 909 +/- 272 micromol x L(-1) x day(-1)). The concentration of whole blood GSH also was decreased in the septic group (665.4 +/- 194 vs. 1059 +/- 334 microM; p <.01)


CONCLUSIONS
Whole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.
Lyons
J
J
Department of Anesthesia, Children's Hospital, Boston, MA, USA.
Rauh-Pfeiffer
A
A
Ming-Yu
Y
Y
Lu
X M
XM
Zurakowski
D
D
Curley
M
M
Collier
S
S
Duggan
C
C
Nurko
S
S
Thompson
J
J
Ajami
A
A
Borgonha
S
S
Young
V R
VR
Castillo
L
L
D000293:Adolescent; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003545:Cysteine / Q000378:metabolism*; D002149:Energy Intake; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000096:biosynthesis / Q000097:blood*; D006801:Humans; D007223:Infant; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000378:metabolism*
D005978:Glutathione; D003545:Cysteine