Effects of Induced Hypothermia on Respiratory parameters and Immunological function

Induced hypothermia is increasingly applied as a therapeutic intervention in
Intensive Care Units. Despite this increase in use of induced hypothermia in
critically ill patients, clinical observations on the effect of hypothermia on
lung mechanics and gas exchange during mechanical ventilation are limited.
Animal experiments suggest a reduction in metabolism with subsequent reduction
of CO2 production. Low tidal volume ventilation is protective in acute lung
injury. It is very well possible that hypothermia may allow for even further
reduction of minute ventilation while maintaining gas exchange, thereby
decreasing mechanical stress caused by mechanical ventilation. Also,
hypothermia protects from ventilator induced lung injury (VILI) by reduction of
leukocyte influx and attenuation of cytokine responses in experimental murine
models. Therefore, hypothermia may be a new therapy for patients with acute
lung injury.
Although a persistent increase in infectious complications have not been
reported, application of hypothermia may hamper immunologic responses.
Increasing the knowledge on the effects of hypothermia on host response will
result in the safe application of hypothermia.

Observational part on respiratory parameters

The primary objective of this study is to study the effect of hypothermia and
rewarming on P/F ratio as a measure of oxygenation and on end tidal CO2 as a
measure of ventilation during mechanical ventilation.

Secondary objectives of this study are to study the effect of hypothermia and
rewarming on:
- static lung compliance
- dead space ventilation
- oxygen consumption (cardiac output x (CaO2-CvO2))
- lung injury score
- oxygenation index ((FiO2 * mean airway pressure) / PaO2)

Case control part on immunologic function

Secondary objectives are to study the effect of hypothermia on immunologic
parameters by comparison with normothermic critically ill patients and healthy
controls, including the effect on:
- The response of blood leucocytes to stimulation with Toll like receptor
ligands (lipopolysaccharide, lipoteicoic acid),
- Toll-like receptor expression profile (mRNA and protein),
- Levels of pro-inflammatory cytokines (IL1β/IL6/TNFα/IFNγ), chemokines (IL8)
and neutrophil degranulation product elastase,
- Expression of monocyte HLA-DR.
- Leukocyte differentiation

A prospective, observational cohort study in the Academic Medical Centre, in
which we will include 50 patients in whom hypothermia is induced after cardiac
arrest and who are admitted to the ICU.
Mechanical ventilation will be adjusted according to arterial blood gas
results, the same way as is done as part of standard care.

All 50 patients included in the study will receive induced hypothermia for 24
hours plus the standard post-resuscitation care. Blood will be drawn from
catheters, which are already in place as part of the standard patient care. The
following data will be collected from the patient data monitoring system:
previous history, age, gender, weight, length, APACHE II, SAPS II. The
following data will be derived from the ventilator at reaching target
temperature (32-34 °C), after 24 hours of hypothermia and at every centigrade
increase in temperature: tidal volume, minute volume, respiratory rate, FiO2,
level of PEEP, peak inspiratory pressure, plateau pressure, compliance, end
tidal CO2. At these same time points, blood gas analysis will be performed
(extra blood donation of 4 ml).

For the immunological parameters in the case-control part of the study, we will
draw 12 ml of blood from 25 patients in whom hypothermia is induced (derived
from the 50 included patients) at three time points: at reaching target
temperature (32-34 °C), after 24 hours of hypothermia and after rewarming to 37
°C (extra blood donation of 36 ml total). In two control groups (25 critically
ill mechanically ventilated normothermic patients and 10 healthy controls), a
one time blood sample of 12 ml will be drawn.

Outside of standard patient care blood will be drawn from a catheter that is
already in place (a total of maximal 50ml). All ventilator and hemodynamic
parameters can be read from the ventilation equipment or monitor or will be
collected from the electronic patient data monitoring system.
A participating patient will not benefit directly from this observational
study. As knowledge of the effect of hypothermia on the respiratory system en
immunological parameters will increase, future patients in whom hypothermia
will be induced may benefit.