Effect of mechanical ventilation on plasma cytokine concentrations in healthy humans

Mechanical ventilation is commonly used in the anesthetized patient during
surgery or in the critically ill patient on the Intensive Care. It is however
obvious that mechanical ventilation is not a physiological way of breathing
(positive pressure vs negative pressure). Research revealed that mechanical
ventilation in animals and in patients with ARDS can induce an inflammatory
reaction with cytokine release that can contribute to the development of
Ventilation Induced Lung Injury (VILI) and Multi Organ Dysfunction Syndrome
(MODS). However, whether it is just the mechanical ventilation itself or a
combination of interacting factors (ventilation, surgery, already damaged
lungs, etc.) that is responsible for the development of VILI/MODS is not clear.
For this reason, studies in humans with normal pulmonary function, comparing
artificial ventilation with normal physiological, spontaneous respiration are
necessary.

Our primary goal is to compare the effects of a positive pressure mechanical
ventilation with spontaneous breathing on systemic cytokine release in patients
with normal pulmonary function. Secondly, the possible effects of surgery on
the ventilation induced systemic cytokine release will be studied.

In 36 healthy young patients scheduled to undergo diskectomy for intervertebral
disc displacement and planned to receive general anesthesia the systemic
cytokine production is measured on defined time-points before, during and after
surgery.

Patients will undergo general anaesthesia 2 hours before the scheduled start of
the surgical procedure. Anaesthesia will be given according to standardized
protocol. Patients are assigned to one of two patient groups. Group S will be
allowed to breathe spontaneously (as much as possible, but arterial saturation
will be carefully monitored and ventilation support will be provided if
necessary) during the two hours before surgery, Group M will be mechanically
ventilated with ventilator settings commonly used in anesthesia.

In healthy humans the effects of the prolonged anesthesia duration, if present
at all, will be transient. Participation will not likely result in prolonged
hospitalisation or a higher side-effect or complication rate.
This study design allows us to isolate the effect of general anesthesia.
Moreover, comparing spontaneous ventilation (negative-pressure ventilation)
with mechanical ventilation (positive-pressure ventilation) has never been done
before. In our opinion, our study design will allow us to better investigate
the impact of mechanical ventilation on cytokine release.