Intra-stomal and sublingual spectroscopy in septic and non-septic Intensive Care patients; effect of Nitroglycerine, Phenylephrine and Norepinephrine.

Global and local intestinal ischaemia is a serious threat to Intensive Care
Unit (ICU) patients. Global intestinal ischaemia is a potential precursor of
sepsis and multiple organ failure (Crit Care. 2005;9 Suppl 4:S13-9. Epub 2005
Aug 25). Diagnosing intestinal ischaemia in the ICU setting is a problem. Scopy
is often difficult; bowel preparation beiing absent or inadequate. Also, only a
limited part of intestine can be observed with coloscopy. Serum lactate is only
an indirect diagnostic parameter. Recently, orthogonal polarisation
spectroscopy (OPS) has been used as a monitor of microcirculation in stoma's of
ICU patients (Crit Care Med. 2007 Apr;35(4):1055-60). Other studies
investigated OPS/SDF sublingual in septic Intensive Care patients, and the
effect of various vasotonic agents. However, OPS does not give information
about the tissue oxygenation, as Near Infrared Spectroscopy (NIRS) does. NIRS
has been validated for Hypovolaemic shock states on the thenar eminence of
trauma patients. We hypothesise, that NIRS could be a potential instrument to
detect intestinal ischaemia via stoma, and monitor the effects of often used
vasotonic drugs on the ICU, such as nitrogglycerine (NTG), Phenylephrine (PE)
and Norepinephrine (NA). Differences between septic and non-septic patients
need to be studied, as changes in microcirculation in septic patients could
potentially influence drug effect. Furthermore, correlations of sublingual NIRS
data will be compared with NIRS data in stoma's, and OPS/SDF data in the
literature.

What is the base-line StO2 reference value in intestinal stoma's. ?
Is NIRS a reliable detector of intestinal ischamia ?
What is the influence of filling-status on StO2 in the stoma and sublingually ?
What is the influence of NTG on StO2 in the stoma and sublingually ?
What is the influence of PE on StO2 in the stoma and sublingually ?
What is the influence of NA on StO2 in the stoma and sublingually ?
Is there a difference in StO2 baseline and intervention values, betweeen septic
and non-septic patients ?
What is the correlation between StO2 in stoma and sublingually, on day 1 resp
day 3 ?
What is the correlation between NIRS data in the stoma and sublingual, and
SDF/OPS data in the literature ?
What is the correlation between NIRS data and systemic haemodynamic parameters
?

Twenty four ICU patients with an enterostomie will be included in the study.
Fifty percent of patients will be septic (ESICM criteria) and 50 % non-septic.
Both mechanically ventilated patients and patients with spontaneous ventilation
will be included. Patients with spontaneous ventilation can be on or off the
ventilator.
Non-invasive cardiac output/index measurement via arterial Pulse Contour
Analysis technique (Vigileo ® by Edwards). Patients will have routine arterial
cannulation.
Serum lactate base-line via arterial catheter (this is already routine on our
ICU).
If the patient has a Central Venous Catheter (CVC), a SvO2 or mixed venous
saturation wil be measured pre and during interventions. CVC will not be
introduced specifically for this study. Baseline haemodynamic parameters and
SvO2. Baseline NIRS measurement on the thenar eminence.
Measurements of baseline physiologic fluctuations of NIRS data in stoma for a
period of 30 minutes. Base line values of NIRS sublingually.
Because NIRS data are not validated for this application, these data may not
influence clinical decision making. Therefore, NIRS data will be unavailable
to, and shielded from, attending clinicians.
Intravascular fluid status will be assessed with a "passive leg raising test"
(PLRT).
Patients are randomised in four equal groups: 1) septic patients receiving
Norepinephrine (NE) respectively Nitroglycerine (NTG); 2) septic patients
receiving Phenylephrine (PE) resp. NTG ; 3) non-septic patients receiving NE
resp. NTG; 4) non-septic patients receiving PE resp. NTG. If NE is already
given, the dose is increased. Effect of fluid optimalisation on NIRS data in
stoma and sublingually.
With a titrating-to-effect-technique, starting with a low dose continuous
infusion, a change of 10 * 20 % in mean arterial pressure (MAP) is generated
(decrease with NTG; increase with PE and NE). After 10 minutes of "steady
state", StO2 in the stoma and sublingually are measured. Also, SvO2 is measured
if patient has a CVC. After 15 minutes of "wash out", the second vasotonic
agent is started. The MAP has to be > 60 mmHg and < 100 mmHg at all times.
Atropine 0.5 mg and Ephedrine 5 mg iv are "stand by" as rescue medication. If
*rescue medication* is administered, a wash out period of 15 minutes will be
applied. Patient will have a minimum of 2 adequate infusions with a minimum
Gauge of 18. NTG, PE and NE can be infused via peripheral infusions as long as
infusion time is short (< 1 h).
Nitroglycerine: start 0,5 ug/kg/min.
Phenylephrine challenge: start 0,1. ug/kg/min.
Norepinephrine: start 0,1 ug/kg/min or increase in septic patients.
After second vasotonic agent: stop study.
On day 3: base line measurements of NIRS data in stoma and sublingually.

Introduction NIRS and SDF probe/sensor in stoma.
"Passive Leg raising".
Optimalisation filling status with colloids with "Fluid Challenge".
Application of NTG, PE and NA.

See also E9A.

Introduction of NIRS probe in stoma and sublingually. NTG, PE and NA can
influence Blood Pressure (BP), depening on Left Ventricular End Diastolic
Pressures (LVEDP). NTG, PE and NA infusions are routine on the ICU and the
Operation Ward. Haemodynamic monitoring will be done with invasive and
continious arterial blood pressure monitoring. LVEDP will be optimalised. NTG,
PE and NA will be titrated to effect and have very short effect life. Stopping
the infusion will halt the effect on BP quickly.