Nociceptive and stress hormonal state during hysterectomy as an index of pain perception: a prospective study.

Hysterectomy is the most frequently performed major gynaecologic surgical
procedure annually throughout the world. The annual number of women undergoing
hysterectomy in the Netherlands is about 15.000.
The most common indication for hysterectomy is uterine fibroids, followed by
dysfunctional uterine bleeding and endometriosis. The three types of
hysterectomy are now used - abdominal, vaginal, and laparoscopic.
Traditionally, abdominal hysterectomy (AH) has been used for gynaecological
malignancy or if the uterus is enlarged. Vaginal hysterectomy (VH) was
originally used only for prolapse, but it is now also used for menstrual
abnormalities when the uterus is of fairly normal size. Laparoscopic
hysterectomy (LH) has been introduced in 1989 as an alternative to abdominal
hysterectomy. However, LH requires other technical skills than the vaginal or
abdominal method.
Several studies compared the three methods stated above in detail.
Significantly improved outcomes suggested that VH should be performed in
preference to AH whenever possible. LH can avoid the abdominal approach and
shows benefits in lower intraoperative blood loss, smaller drop in hemoglobin
level, shorter duration of hospital stay, speedier return to normal activities,
fewer wound or abdominal wall infections, fewer unspecified infections,
however, at the cost of longer operating time and more urinary tract (bladder
or ureter) injuries. In contrast, according to relative elevated IL-6 and CRP
serum levels found in AH, this abdominal approach is repeatedly associated with
inclined tissue damage.

Still a debate is continuing concerning the method of preference in
hysterectomies when a vaginal approach is contraindicated. A recent Dutch
preference study concluded that patients prefer the safest as well as the
laparoscopic method. Although after surgery LH patients report to be pain free
in a significant shorter period of time compared to AH, recent studies observed
that laparoscopic surgery is associated with higher pain scores in the first
hours postoperatively. Due to minimal access, the laparoscopic approach is
proved to cause less tissue damage. Still patients appear to report heavier
pain immediately after the procedure. In addition, as minimal invasive surgery
is associated with minimal (tissue) damage, should it therefore cause minimal
pain impulses during and after the intervention? A novel approach in measuring
nociceptive impulses as an index of pain perception during surgery has recently
been validated.
To our knowledge no research on evaluation of stress hormone levels in patients
undergoing the different modes of hysterectomy has been published yet. Measured
stress hormones (e.g. catecholamine) might be accompanying predictors of
experienced intraoperative pain. Previous research indicated that a minimal
invasive approach in surgery is associated with lower intraoperative stress
hormone levels. According to one recent study the depth of anesthesia does not
influence the endocrine-metabolic response to pelvic surgery, thus suggesting
that the results from the three different to be studied approaches should be
fairly comparable.

This study primarily aims to get insight in the intraoperative nociceptive
state of the patient as an index of the amount of pain stimuli comparing the
three modes of hysterectomy. Next to this, by measuring pre-, intra- and
postoperative stress hormone levels this study aims to emphasize whether these
levels differ between the three modes of hysterectomy.

In this prospective single center study every consecutive hysterectomy
(vaginal, abdominal or laparoscopic) will be included.

Nociceptive state monitoring
In order to compute the nociceptive state the pulse transit time (PTT, defined
as the time between the R-wave of the ECG and the arrival of the pulse wave in
the periphery (e.g. finger tip)) is measured as an index of pain perception.
Previous studies show that PTT gives a better indication of the nociceptive
state than commonly used parameters, such as blood pressure, heart rate and
processed EEG monitoring.

Hormonal state monitoring
Pre-, intra- and postoperatively blood samples will be collected in order to
measure stress hormone levels. In total six blood samples will be collected, of
which three will be taken during regular control moments (see figure 1) The
remaining three samples will be collected during surgery. Plasma catecholamine
concentration (C-CAMI; norepinephrine and epinephrine levels) will be measured.
Each obtained sample consists of 4 ml blood and will be kept in an EDTA-fuse,
stored in a minus 20 degrees Celsius environment for further analysis.


Postoperative pain reporting
As an extra check every patient will be asked to assess her pain level using a
VAS (1-10) preoperatively (before pre-medication has been administered) and one
hour postoperatively, provided she self-rates herself awake (>4-10 VAS).
Otherwise attempts will be made by the PACU physician or nurse, every 15
minutes until awake.
Pain-medication of each patient will be registered.

Power calculation
Provided patients undergoing a LH will experience more pain durante operationem
and
during the first 4 hours postoperatively compared to the AH-group we want to
assess a
30% mean difference (α = 0.05) in PTT during surgery, with SD 0.2. Based on the
results from the pilot study, we need 15 patients in each group to achieve a
power of 0.98. The VH-group will primarily act as a control group, as
unfortunately no adequate comparable research on pain perception in vaginal
surgery is available yet.

Informed consent
As in this study several blood samples will be collected and participation of
the patient is needed, regarding her cooperation in assessing pain intensities
using the VAS pre- and postoperatively, an informed consent is a requisite.

N.A.