Primary Objective: - To identify relative IL-6 thresholds (% increase from baseline and % decrease from the peak postoperative value) for predicting infectious complications after pulmonary surgerySecondary Objective(s): - To identify relative IL-6…
ID
Source
Brief title
Condition
- Other condition
- Respiratory tract neoplasms
- Respiratory tract therapeutic procedures
Synonym
Health condition
postoperatieve complicaties
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters are levels of IL-6, CRP, leucocyte count, PCT, ntproBNP,
GDF-15 and hs-cTn.
Primary endpoint is the development of an infectious complication which is
defined as one of the following outcomes within 30 days of surgery:
- pneumonia (purulent sputum, positive sputum or blood culture and clinical
symptoms such as cough, fever or consolidation on chest radiograph)
- pulmonary empyema (pleural effusion and the presence of pus on pleural
aspiration, microorganism on pleural fluid culture or positive pleural fluid
Gram stain)
- sepsis (qSOFA score >=2 in response to an infection)
- wound infection (purulent drainage from superficial incision or deliberate
opening of superficial incision by surgeon and pain, tenderness, swelling or
redness)
- urinary tract infection (urinary tract symptoms or fever and urine culture
with no more than 2 species of organisms identified with at least one of which
is a bacterium of >=105 CFU/ml)
Secondary outcome
Secondary endpoint is the development of a non-infectious complication which is
defined as one of the following outcomes within 30 days of surgery:
- acute kidney injury (increase in serum creatinine by >= 26 µmol/l, a
percentage increase in serum creatinine of more than or equal to 50% or
oliguria of less than 0.5 ml/kg per hour for more than six hours within 48
hours)
- respiratory insufficiency (hypoxia or hypercapnia leading to ICU
(re)admission)
- reoperation
- supraventricular arrhythmia (new-onset atrial fibrillation or atrial flutter)
- congestive heart failure (pleural effusion or pulmonary edema requiring
diuretic therapy)
- acute respiratory distress syndrome (defined as diffuse inflammatory lung
injury (onset over 1 week or less), bilateral opacities consistent with
pulmonary edema must be present and may be detected on CT or chest radiograph,
PF ratio <300mmHg with a minimum of 5 cmH20 PEEP (or CPAP) must not be fully
explained by cardiac failure or fluid overload
- pulmonary embolus (filling defect >= 75% in a pulmonary artery with
corresponding normal ventilation
- stroke (clinical diagnosis of acute transient ischemic attack (TIA) or
cerebrovascular accident (CVA))
- myocardial infarction (elevated hs-cTn in combination with clinical symptoms
or electrocardiography changes)
- mortality
Other secondary endpoints that will be captured are any complication (which is
a composite of infectious and non-infectious complications within 30 days of
surgery), length of ICU stay and length of hospital stay.
For both the primary and secondary endpoints the exact time (in hours and days
after surgery, and during or after ICU admission) on which the endpoint is
reached will be noted.
Background summary
Up to 50% of patients undergoing pulmonary surgery for cancer suffer from
complications such as pneumonia, respiratory insufficiency, cardiac arrhythmia
and death. Postoperative complications are a major determinant of survival up
to five years after surgery and therefore a potential target to improve
surgical outcome.
Currently, the identification of patients at high risk of postoperative
complications is often based on levels of proinflammatory biomarkers, such as
levels of C-reactive protein (CRP) and leucocyte count. Unfortunately, the
specificity and sensitivity for the prediction of complications in the first
days following surgery is relatively low. This can be partly explained by the
slow change of CRP levels and leucocyte count in response to an inflammatory
insult.
Interleukin-6 (IL-6) is a proinflammatory biomarker that is produced by
monocytes in response to tissue injury. Levels of IL-6 increase within 60
minutes, peak after 4 to 6 hours and usually return rapidly to baseline due to
the short plasma half-life of 2 to 6 hours (compared to 19 hours for CRP). In a
recent study, levels of IL-6 on postoperative day 1 had a similar diagnostic
accuracy as levels of CRP on postoperative day 3 for the prediction of
complications following major abdominal surgery. This may suggest that
introducing IL-6 measurements after surgery may lead to an earlier detection of
complications and possibly improved long-term outcome.
Until now, clinicians have focussed on absolute peak levels of proinflammatory
biomarkers during the immediate postoperative period. The underlying idea is
that inflammation induced by surgical trauma is harmful when the inflammatory
response is excessive. However, there is a great variation in levels of
proinflammatory biomarkers between patients and peak levels of proinflammatory
biomarkers have low diagnostic value for the prediction of postoperative
complications. It is possible that changes in levels of inflammatory biomarkers
over time have a higher discriminative power for identifying patients at high
or low risk of postoperative complications than absolute peak levels. For
example, an initial proinflammatory biomarker peak on the first postoperative
day followed by a rapid decline to baseline in the following days after surgery
may indicate a physiological, innocent inflammatory response, while a sustained
elevation points to an increased risk of complications. Given the vivid
dynamics and rapid changes over time, levels of IL-6 appear to be the most
useful marker to study this hypothesis.
Study objective
Primary Objective:
- To identify relative IL-6 thresholds (% increase from baseline and % decrease
from the peak postoperative value) for predicting infectious complications
after pulmonary surgery
Secondary Objective(s):
- To identify relative IL-6 thresholds for predicting non-infectious
complications and any complication (a composite of infectious and
non-infectious complications) after pulmonary surgery
- To compare the prognostic accuracy of relative IL-6 thresholds for predicting
infectious, non-infectious and any postoperative complication to other
biomarkers as CRP, leucocyte count, procalcitonin (PCT), ntproBNP, GDF-15 and
high-sensitive cardiac troponin (hs-cTn)
Study design
Multicentre prospective observational cohort study with a follow up time of 30
days after surgery. Patients will be included in the Amphia Hospital, Breda and
the St. Antonius Hospital, Nieuwegein.
Study burden and risks
In each patient seven blood samples will be drawn for analysis. During the
first 24 hours blood samples will be collected using an arterial line which is
routinely used in patients undergoing lung surgery. On day two and three blood
samples will be drawn simultaneously with standard postoperative sampling.
There are no direct risks or benefits for patients included in the study.
Clinicians are blinded for the laboratory results determined for the purpose of
this study. The test results will therefore not affect treatment of study
patients.
Molengracht 21
Breda 4818 CK
NL
Molengracht 21
Breda 4818 CK
NL
Listed location countries
Age
Inclusion criteria
Elective pulmonary surgery (pneumonectomy, (bi)(sleeve)lobectomy, segmentectomy) for cancer, American Society of Anesthesiologists (ASA) physical status classification >=2 with a planned postoperative admission to the Intensive Care.
Exclusion criteria
(suspected) Infection at the time of surgery and reoperation within 24 hours of surgery
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL64754.101.18 |