82. Activated Protein C Reduces Proinflammatory Cytokines and Preserves Renal Function After Trauma...
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Transcript of 82. Activated Protein C Reduces Proinflammatory Cytokines and Preserves Renal Function After Trauma...
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82. ACTIVATED PROTEIN C REDUCES PROINFLAMMA-TORY CYTOKINES AND PRESERVES RENAL FUNC-TION AFTER TRAUMA AND SEPSIS. Steve Keller1, ToanHuynh1, Susan Evans1, Mark Clemens2; 1Carolinas MedicalCenter, Charlotte, NC; 2The University of North Carolina atCharlotte, Charlotte, NC
Introduction: In this study, we sought to determine the time-dependent severity of renal dysfunction after cecal ligation andpuncture (CLP). We hypothesized that aPC may restore renalfunction by reducing pro-inflammatory cytokine levels. Methods:Sprague Dawley rats underwent sham or CLP. At 6 or 24 hrs afterinjury, kidney function was assessed by plasma Na�, K�, bloodurea nitrogen (BUN) and creatinine (Cr). In separate studies, twogroups of rats underwent sham or CLP. After 24 hrs, group 1received saline and group 2 received aPC (1mg/kg) for four days.Plasma was harvested for BUN, Cr and LDH levels; IL-2 wasmeasured by ELISA. Results: Plasma electrolytes, BUN and Crwere altered as early as 6 hrs after CLP. Treatment with aPCreduced plasma BUN, Cr and LDH levels. After CLP, IL-2 levelsincreased; aPC treatment attenuated this response (Table).
GroupNa�
(mmol/L)K�
(mmol/L)BUN
(mg/dL)Cr
(mg/dL)
Sham 133 � 2 3.6 � 0.2 14 � 1 0.06 � 0.03CLP (6hr) 143 � 1* 5.3 � 0.4* 22 � 1* 0.4 � 0.04*CLP (24hr) 139 � 2* 5.6 � 0.2* 29 � 4*† 0.4 � 0.04*Group IL-2
(pg/mL)BUN
(mg/dL)Cr
(mg/dL)LDH(IU/L)
Sham �saline
68 � 2 14 � 0.6 0.06 � 0.04 231 � 49
Sham �aPC
77 � 8 12 � 1 0.03 � 0.02 219 � 34
CLP �saline
167 � 39* 73 � 16* 0.42 � 0.01* 544 � 56*
CLP � aPC 101 � 17§ 24 � 3§ 0.03 � 0.02§ 262 � 72§
* p�0.05 vs. sham.† p�0.05 vs. CLP (6hr).§ p�0.05 vs. CLP�saline; n�4-5/group.
Conclusion: Our data suggest that renal dysfunction occurs 6hours after onset of sepsis; and continues to decline thereafter.Treatment with aPC attenuated IL-2 levels and restored renalfunction. Thus, aPC may confer survival advantage by reducingsystemic inflammation and preserving organ function.
83. ABNORMAL INSULIN SENSITIVITY PERSISTS UP TOTHREE YEARS IN PEDIATRIC PATIENTS POST BURN.Gerd Gauglitz, David Herndon, Gabriela Kulp, Marc Jeschke;Shriners Hospitals for Children, Galveston, TX
Introduction: The period following severe burn is characterized byinsulin resistance and hyperglycemia. It is presently unknown howlong these conditions persist beyond the acute phase post-injury. Inthis study, we examined the extent and persistence of abnormalitiesof various clinical parameters commonly utilized to assess the degreeof insulin resistance in a large pediatric population post burn up tothree years. Methods: A population of 147 severely burned pedi-atric patients was included in the present study. A standard 75 goral glucose tolerance test was performed during patient hospitalstay and at 3, 6, 9, 12, and up to 36 months post burn. Glucoseuptake and insulin secretion were assessed by measuring serumglucose, insulin and C-peptide following the glucose load usingstandard methodologies. Insulin resistance/sensitivity indices(ISI Matsuda, ISI Quicky, HOMA, ISI Cederholm) were calculated
from the measured serum values. Values obtained were comparedto a set of 60 children without trauma or burn. Statistical analysiswas performed by ANOVA with Bonferroni’s correction with sig-nificance accepted at p�0.05. Results: During their hospital stayand up to 3 - 6 months, the burned population displayed signifi-cantly augmented levels of glucose, insulin and C-peptide com-pared to the control group. Interestingly, although glucose levelsreturned to normal values subsequently, the levels of insulin andC-peptide remained elevated throughout the entire length of thestudy. Both insulin resistance/sensitivity indices, Matsuda andQuicky, were indicative of pathology in burned patients from thebeginning of the study up to 12 months post-burn, demonstratingwhole body insulin resistance during the first year after injury.The HOMA index returned to normal values after 24 months,indicating that hepatic insulin resistance had subdued. In con-trast, the ISI Cederholm index remained within pathological val-ues throughout the entire study, suggesting that peripheral insu-lin resistance was present in children up to 3 years post burn.Conclusion: Pathologic response to insulin is a hallmark of theacute phase in patients post burn. In this study, we have demon-strated that alterations in insulin sensitivity persist up to 3 yearsafter the burn injury, although the patients do not display clinicaldiabetes.
84. MINIMALLY INVASIVE HEMODYNAMIC AND VOLU-METRIC MONITORING IN SEVERELY BURNED PEDI-ATRIC PATIENTS: A PROSPECTIVE COHORT STUDY.Ludwik K. Branski, Marc G. Jeschke, Jaron F. Byrd, Arthur P.Sanford, Felicia N. Williams, William B. Norbury, David N.Herndon; Shriners Hospital for Children and University ofTexas Medical Branch, Galveston, TX
Introduction: Severe burns in pediatric patients have a majorimpact on cardiac and pulmonary function. Appropriate monitor-ing and treatment is crucial during the acute ICU admission;however, the use of pulmonary catheters, especially in pediatricpatients, has been associated with many risks. We sought todetermine the development of important hemodynamic and volu-metric parameters in severely burned patients during their acuteadmission, using the minimally invasive transpulmonary ther-modilution technique with continuous pulse contour analysis.Methods: The present prospective cohort study was conductedbetween December 2005 and April 2007 in consecutive patientswith severe burns over 40% Total Body Surface Area (TBSA),admitted within 48h after the burn injury to the Shriners Hospitalfor Children, Galveston, TX. Transpulmonary thermodilutionmeasurements were performed using the PiCCO system. Param-eters measured by thermodilution included Cardiac Index (CI),Intrathoracic Blood Volume Index (ITBVI), and ExtravascularLung Water Index (EVLWI); Systemic Vascular Resistance Index(SVRI) was determined continuously by arterial pulse contouranalysis. Measurements were recorded twice daily, starting 72hpost burn (baseline), and continued until 28 days post burn orpatient discharge, whichever occurred earlier. Statistical analysiswas performed using one-way repeated measures ANOVA withpost-hoc Bonferroni’s test for intra-group comparisons to baselinevalues. Results: A total of 46 patients with a mean age of 9�5years and a mean TBSA burn of 66%�17% (56%�25% full thick-ness burn) were studied. Thirty-five of the patients (76%) with amean TBSA burn of 61%�16% (49%�24% full thickness burn)survived the burn injury and were included in the analysis. Con-tinuous significant increase of CI was found starting at nine dayspost burn, and remained elevated throughout the entire measure-ment period (baseline: 5.8�1.3 L/min/m2, day 9: 6.8�1.3 L/min/m2, day 21: 7.4�1.3 L/min/m2, day 28: 7.6�1.3 L/min/m2, allp�0.004). The preload parameter ITBVI increased significantlystarting at ten days post burn (baseline: 696�267 ml/m2, day 10:1037�328 ml/m2, day 21: 975�213 ml/m2, day 28: 1113�353 ml/
213ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS