The aim of this study is to access the effect of low and high VT (ml/kg) on pulmonary and systemic inflammatory responses and the release of oxygen and nitrogen free radicals in the paediatric patient with and without ALI.
ID
Source
Brief title
Condition
- Other condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Health condition
Innate immuunresponse
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the effect of low and high VT (ml/kg) on pulmonary and
systemic inflammatory responses and the release of oxygen and nitrogen free
radicals determined in deep tracheal aspirate and in plasma respectively, in
the paediatric patient with and without ALI.
Secondary outcome
Secondary endpoints are the effects of low and high VT (ml/kg) HA on
hemodynamics and pulmonary gas exchange.
Background summary
Acute lung injury (ALI) is a major cause of acute respiratory failure in
children with a mortality ranging from 5-35%. Mechanical ventilation (MV) may
be an important factor contributing to lung injury and the subsequent mortality
by inducing the release of inflammatory mediators and the generation of oxygen
and nitrogen free radicals.
Studies remain controversial whether MV by itself or only in the presence of
ALI can release inflammatory cytokines.
Lung protective ventilation in order to prevent VILI has been predominantly
studied in adults with ALI or ARDS and is based on a combination of limited
inspiratory pressures and/or tidal volumes (V T). Clinical trials in adults
have demonstrated a decrease in the inflammatory response and mortality with
this strategy. Controversies exist whether patients without pre-existent lung
injury will benefit from MV with a lower VT.
To our knowledge, no published trials to date have compared the use of low VT
ventilation strategies with high VT ventilation in paediatric patients with or
without ALI.
Study objective
The aim of this study is to access the effect of low and high VT (ml/kg) on
pulmonary and systemic inflammatory responses and the release of oxygen and
nitrogen free radicals in the paediatric patient with and without ALI.
Study design
Prospective intervention cross-over study.
Intervention
After inclusion patients will be ventilated for a period of 6 hours with a PEEP
of 7 cm H2O and VT of 8 ml/kg predicted body weight (*wash in period*).
Following these 6 hours patients will be randomized to a group were MV will be
changed first to a *lung protective* setting with PEEP of 10 cm H2O and VT of 6
ml/kg followed by a more *conventional* ventilator setting with PEEP of 4 cm
H2O and VT of 10 ml/kg for a period of 6 hours or to a group starting with a
*conventional* setting followed by a *lung protective* setting.
Study burden and risks
The risks of this study are negligible and the burden minimal, mostly because
treatment and monitoring are part of routine care on our PICU. All patients are
sedated and will have an arterial catheter in place in accordance with standard
clinical care, so the patient will not experience any discomfort. There will be
no direct benefit for the patients examined, but the results of this study
might be of benefit for other children in the future. This study will provide
important insight in the pathophysiological mechanisms underlying VILI in
children and may guide future research and potentially improve ventilation
strategies in children and their outcome.
Geert Grooteplein 10
6500 HB Nijmegen
Nederland
Geert Grooteplein 10
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
1. Children between the age of 2 months and 2 years admitted to the PICU and requiring MV with ALI and non ALI.
ALI is defined as:
- Bilateral infiltration seen on frontal chest radiograph
- No clinical evidence of left atrial hypertension
- Partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio of less than 300 mmHg
2. Patients on ventilatory support not exceeding 72 hours before inclusion of the study.
3. The expected duration of ventilation should be minimal 24 hours.
4. Patients should be ventilated by the Pressure Regulated Volume Controle (PRVC) mode.
Exclusion criteria
• No informed consent from the patient*s legal representative
• Expected survival < 2 days
• Infants < 2 months of age and infants > 2 years
• Use of corticosteroids < 6 weeks before the start or during the study
• Immunocompromised patients
• Critical pulmonary or cardiac function documented by an FiO2/PaO2 ratio
< 100 mmHg or need of catecholamines for inotropic support
defined as norepinephrine > 0.5 microgram/kg/min in spite of adequate fluid
resuscitation
• Pneumothorax proven by chest X-ray.
• Severe chest deformations (open sternum, flial chest, kyphoscoliosis)
• Chronic hypoxemic lung disease
• Cyanotic congenital heart disease
• Cardiac failure as a primary cause of lung disease
• Patients who had received a bone marrow or lung transplantation
• Patients with increased intracranial pressure
• Patients who had participated in other clinical trials involving acute lung
injury within the preceding 30 days.
• Severe chronic liver disease (as defined by Child-Pugh class C)
• Patients after cardiac resuscitation
• Patients with a decision to limit life support.
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 | NL27046.000.09 |