Clinical trial NCT00929448: The Predictive Value of Clinical and Immunological Factors in the Development of Pneumonia After Traumatic Brain Injury
Official title: The Predictive Value of Clinical and Immunological Factors in the Development of Pneumonia After Traumatic Brain Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Traumatic Brain Injury
Keywords: Traumatic brain injury
Lead sponsor: Royal Alexandra Hospital
Sponsor class: OTHER
First posted: 2009-06-29
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Intensive Care

Brief summary: The development of pneumonia and other infections is one of the most common complications of a traumatic brain injury (TBI). Prior studies have also found that patients suffering from TBI also develop immune dysfunction consistent with an immunosuppressed state shortly after the traumatic event. Specifically, it has been shown that patients with a TBI have impaired delayed type hypersensitivity (DTH), cellular immunity and humoral immunity. The humoral arm of the immune system is particularly involved in defending the host against extracellular bacteria and is primarily composed of B-cells, immunoglobulins and complement. Surgery and trauma impair the clonal expansion of antibody producing B lymphocytes causing hypogammaglobulinemia, through a mechanism involving T lymphocytes. In addition, during the systemic inflammatory process, pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1beta) and interleukin 6 (IL-6) are released. Nuclear factor kappa beta (NF-kB) is a transcriptional regulatory protein that is involved in the expression of proinflammatory cytokines and appears to act at a critical step in the transcription of many proinflammatory genes.

The hypothesis of this study is that the hypogammaglobulinemia from the immune dysfunction and the induction of NF-kB from the inflammatory process are, in part, responsible for the development of pneumonia and other infectious complications identified after TBI. This study has two specific aims: The primary specific aim of this study is to determine the association between serum immunoglobulin or NF-kB levels and the development of pneumonia in patients suffering from traumatic brain injury (TBI). The secondary specific aim of this study is to determine the relative contribution of clinical variables such as APACHE II-III Score and Injury Severity Score as compared to immunological variables (serum immunoglobulins and NF-kB) to the development of pneumonia in patients suffering from TBI.


Eligibility criteria: Inclusion Criteria:

* \> 18 yrs
* Admitted to ICU in Capital Health region with a TBI and \> 1 of the following:
* An initial resuscitated (Sys BP\>90 mmHg and O2 Sat \>90%) GSC of ≤ 8
* A post resuscitation (Sys BP\>90 mmHg and O2 Sat \>90%) GCS at presentation to the hospital of ≤ 8 in the absence of sedation
* A post resuscitation (Sys BP\>90 mmHg and O2 Sat \>90%) GCS within 72 hrs of hospital admission of ≤ 8 in the absence of sedation
* Intracranial pressure monitoring
* Decompressive craniectomy
* Presence of subfalcine, uncal, or supratentorial herniation either clinically or radiologically

Exclusion Criteria:

* Longer than 5 days since ictus of TBI

Primary outcomes:
measure: The primary outcome of this study will be the development of the composite of either early onset pneumonia (EOP) or ventilator associated pneumonia (VAP
timeFrame: baseline, d4, d7, d10, d14
Secondary outcomes:
measure: Secondary outcomes will include ICU and hospital mortality and LOS, duration of mechanical ventilation, Glasgow Outcome Score (GOS) at hospital discharge and at 6-months, and 1-year.
timeFrame: hospital discharge
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
Study officials:
affiliation: Royal Alexandra Hospital
name: Demetrios Kutsogiannis, MD
role: PRINCIPAL_INVESTIGATOR
References: