Chest
Volume 111, Issue 5, May 1997, Pages 1306-1321
Journal home page for Chest

Clinical Investigations in Critical Care
Infections and the Inflammatory Response in Acute Respiratory Distress Syndrome

https://doi.org/10.1378/chest.111.5.1306Get rights and content

Study objective

Systemic inflammatory response syndrome (SIRS) and infections are frequently associated with the development and progression of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). We investigated, at onset and during the progression of ARDS, the relationships among (1) clinical variables and biological markers of SIRS, (2) infections defined by strict criteria, and (3) patient outcome. Biological markers of SIRS included serial measurements of inflammatory cytokines (IC)—tumor necrosis factor-α (TNF-α) and interleukins (IL) 1β, 2, 4, 6, and 8—in plasma and RAL fluid.

Methods

We prospectively studied two groups of ARDS patients: 34 patients treated conventionally (group 1) and nine patients who received glucocorticoid rescue treatment for unresolving ARDS (group 2). Individual SIRS criteria and SIRS composite score were recorded daily for all patients. Plasma IC levels were measured by enzyme-linked immunosorbent assay on days 1, 2,3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients received mechanical ventilation. Unless contraindicated, bilateral BAL was performed on day 1, weekly, and when ventilator-associated pneumonia was suspected. Patients were closely monitored for the development of nosocomial infections (NIs).

Results

ICU mortality was similar among patients with and without sepsis on admission (54% vs 40%; p<0.45). Among patients with sepsis-induced ARDS, mortality was higher in those who subsequently developed NIs (71% vs 18%; p<0.05). At the onset of ARDS, plasma TNF-α, IL-1β, IL-6, and IL-8 levels were significantly higher (p<0.0001) in nonsurvivors (NS) and in those with sepsis (p<0.0001). The NS group, contrary to survivors (S), had persistently elevated plasma IC levels over time. In 17 patients, 36 definitive NIs (17 in group 1 and 19 in group 2) were diagnosed by strict criteria. No definitive or presumed NIs caused an increase in plasma IC levels above patients’ preinfection baseline. Daily SIRS components and SIRS composite scores were similar among S and NS and among patients with and without sepsis-induced ARDS, were unaffected by the development of NI, and did not correlate with plasma IC levels.

Conclusions

Sepsis as a precipitating cause of ARDS was associated with higher plasma IC levels. However, NIs were not associated with an increase in SIRS composite scores, individual SIRS criteria, or plasma IC levels above patients’ preinfection baseline. SIRS composite scores over time were similar in S and NS. SIRS criteria, including fever, were found to be nonspecific for NI. Irrespective of etiology of ARDS, plasma IC levels, but not clinical criteria, correlated with patient outcome. These findings suggest that final outcome in patients with ARDS is related to the magnitude and duration of the host inflammatory response and is independent of the precipitating cause of ARDS or the development of intercurrent NIs.

Section snippets

Patients

The study was conducted between January 1992 and May 1993 at the Medical ICU of the Regional Medical Center and the University of Tennessee Medical Center, Memphis. The protocol was approved by the University of Tennessee institutional review board, and informed consent was obtained before entrance into the study. We prospectively studied 43 consecutive patients who developed medical ARDS. Thirty-eight patients were admitted to the ICU directly from the emergency department, and five patients

Clinical Variables at the Onset of ARDS for Groups 1 and 2

Demographics and clinical variables at the onset of ARDS for groups 1 and 2 are shown in Table 1. No significant difference was found between the two groups except for sex, LIS, cardiovascular dysfunction, and the presence of shock. Causes of direct lung injury for group 1 included 17 pneumonia (7 with bacteremia), two chemical aspiration, and one bleomycin-oxygen toxic reaction. Causes of direct lung injury for group 2 included two pneumonia and three chemical aspiration. Causes of indirect

DISCUSSION

The host defense response to an insult is similar, regardless of the tissue involved, and consists of an interactive network of simultaneously activated pathways that act in synergy to increase the chance of survival. The host defense is essentially a protective response of tissues and serves to destroy, dilute, or wall off injurious agents21 and to repair any tissue damage. This repair consists of replacing injured tissue by regenerating parenchymal cells and filling defects with fibroblastic

CONCLUSIONS

Survival in patients with ARDS is related to the magnitude and duration of the host inflammatory response and is independent of the precipitating cause of ARDS or the development of intercurrent NI. We have found no evidence of amplification of the host inflammatory response, as measured by clinical SIRS score or biological plasma IC levels, in the presence of documented or suspected NI. Downregulation in the presence of NI most likely represents cytoprotection from overwhelming cytokinemia and

ACKNOWLEDGMENTS

We wish to thank Drs. John P. Griffin and David Armbruster for editorial assistance; Reba Umberger, RN, and Stephanie Carson, RN, for assistance with data collection; Vicky Franke for secretarial support; and the UT Division of Pulmonary and Critical Care Medicine for assistance with patient recruitment.

REFERENCES (42)

  • NortonL.W.

    Does drainage of intra-abdominal pus reverse multiple organ failure?

    Am J Surg

    (1985)
  • ErtelW. et al.

    Downregulation of proinflammatory cytokine release in whole blood from septic patients

    Blood

    (1995)
  • FowlerA.A. et al.

    Risk with predispositions

    Ann Intern Med

    (1983)
  • PettyT.L.

    Indications of risk, course, and prognosis in adult respiratory distress syndrome [editorial]

    Am Rev Respir Dis

    (1985)
  • Extracorporeal support for respiratory insufficiency: collaborative study

    (1979)
  • MontgomeryA.B. et al.

    Causes of mortality in patients with the adult respiratory distress syndrome

    Am Rev Respir Dis

    (1985)
  • SeidenfeldJ.J. et al.

    Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome

    Am Rev Respir Dis

    (1986)
  • BellR.C. et al.

    Multiple organ system failure and infection in adult respiratory distress syndrome

    Ann Intern Med

    (1983)
  • MeduriG.U. et al.

    New Horizons

    (1993)
  • BoneR.C.

    Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation

    Crit Care Med

    (1996)
  • KnausW.A. et al.

    APACHE II: a severity of disease classification system

    Crit Care Med

    (1985)
  • Cited by (215)

    • Prolonged glucocorticoid treatment in ARDS: Pathobiological rationale and pharmacological principles

      2023, Stress: Immunology and Inflammation: Handbook of Stress Series Volume 5
    View all citing articles on Scopus

    This study was supported by Clinical Research Center grant 5M01RR00211 and Baptist Health Care Foundation grant 9506. This study won a 1994 DuPont Pharmaceuticals American College of Chest Physicians Young Investigator Award (Dr. Headley).

    View full text