The immunomodulatory effects of damage control abdominal packing on local and systemic neutrophil activity

John M. Adams, Carl J. Hauser, David H. Livingston, Zoltan Fekete, George Hasko, Raquel M. Forsythe, Edwin A. Deitch

Research output: Article

35 Citations (Scopus)

Abstract

Background: Damage control laparotomy (DCL) with abdominal packing has become commonplace after major trauma, but the immune consequences of DCL are unknown. Methods: We collected 37 fluid samples from laparotomy pads (LPF) removed from 28 patients 1 hour to 7 days after DCL. Samples from eight patients who underwent serial packing were assayed for their mediator content and effects on neutrophil (PMN) function. Respiratory burst (RB) to N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate (PMA), as well as PMN calcium ([Ca2+]i) mobilization by GRO-α and platelet-activating factor were studied using dihydrorhodamine and fura-2-acetoxymethyl ester fluorescence. Brief exposure to 20% LPF (LPF20) modeled LPF acting on peritoneal PMNs and 2% LPF (LPF2) modeled the systemic effects on PMNs. Endotoxin (ETX), GRO-α, and leukotriene B4 were assayed by enzyme-linked immunosorbent assay. Data analysis was by analysis of variance with Dunn's comparisons or the Mann-Whitney test when indicated. Results: LPF increased N-formyl-methionyl-leucyl-phenylalanine-induced RB from 0.4 ± 0.1 × 103 counts per second (control) to 0.7 ± 0.1 (LPF2) to 1.3 ± 0.3 (LPF20) (p < 0.05), with LPF2 increasingly active at later times after injury. PMA-elicited RB was primed only by LPF2 from < 24 hours. Both LPF2 and LPF20 markedly suppressed GRO-α [Ca2+]i flux. Suppression by LPF2 was maximal at < 24 hours, abating after 48 hours. Suppression of GRO-α response was dose dependent: 150 ± 8 nmol/L in control PMNs, 97 ± 19 after LPF2, and 59 ± 4 after LPF20 (all p < 0.05). [Ca2+]i flux after 1 nmol/L platelet-activating factor was only suppressed (from 181 ± 14 nmol/L to 149 ± 15 nmol/L, p < 0.05) by LPF20. LPF contained ETX, GRO-α, and leukotriene B4 at 10- to 20-fold plasma concentration in trauma patients. Conclusion: DCL results in peritoneal ETX and mediator accumulation even when cultures are sterile. LPF exposure primes PMN RB elicited by nonreceptor- (PMA) or receptor-coupled agonists that resist receptor desensitization. Conversely, LPF suppresses PMN responses to agonists that undergo receptor desensitization at high mediator concentrations. PMN dysfunction in such circumstances probably reflects a concomitant priming of some cell functions (e.g., RB) and desensitization of other (receptor-dependent) functions after an exposure to concentrated mediators. Peritoneal mediator production after DCL may be ETX driven, and may contribute to systemic inflammatory response syndrome. DCL trades early hemostasis for later inflammation. This should be considered in planning management strategies.

Original languageEnglish
Pages (from-to)792-800
Number of pages9
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume50
Issue number5
DOIs
Publication statusPublished - jan. 1 2001

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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