Post-Operative Pain prevention after hepato-pancreato-biliary surgery: continuous sUbfascial infiltration or ePidural analgesia? a randomized controlled non-inferiority multicenter trial

Postoperative pain prevention is essential for the recovery of patients after
surgery. Effective analgesia may prevent complications such as pneumonia,
thromboembolic complications, a prolonged catabolic stage and anxiety among
patients. It can facilitate
early mobilization and may result in earlier recovery.1

Continuous Epidural Analgesia (CEA) is the current standard pain treatment
after laparotomy for hepato-pancreato-biliary (HPB) conditions and other
indications. This is supported by a recent Cochrane systematic review which
concluded that CEA is superior to opioid patient controlled analgesia (PCA) in
relieving postoperative pain for up to 72 hours in patients undergoing
intra-abdominal surgery, but it is associated with a higher incidence of
pruritus.2 Other downsides of CEA are a) the time used to place the epidural
catheter, b) the small risk of epidural complications (hematoma and abscess)3,
c) the postoperative hypotension, frequently requiring additional intravenous
fluid boluses which might delay recovery and d) need for indwelling urinary
catheter. For these reasons alternatives have been explored.

Patient-controlled epidural analgesia (PCEA) is the current best practice. The
benefits compared to CEA are less motor block, less infused volume and patients
are likely to require less anaesthetic intervention. PCEA and CEA have a
similar safety profile.4 Currently, no randomized trial has used PCEA, the
current best practice, in the control arm.

A promising alternative is the continuous i.m. bupivacaine infusion (CSWI) plus
patient-controlled analgesia (PCA). In several high UK volume centers for
hepato-pancreato-biliary surgery (Basingstoke, Edinburgh, Southampton) this has
become the routine approach for all laparotomies. These catheters are placed at
the end of the surgery by the surgeon and are connected to pumps. This
technique combined with PCA does not have the described downsides of CEA.

In a retrospective study , a reduction in length of hospital stay was seen
after major liver resections with the use of the same technique. The pain
control by CSWI + PCA was similar to that provided by CEA. On average patients
were discharged one day earlier (7 vs 8 days). The morbidity was also lower
(26% versus 39%). A drawback of this study is that the patients in the CEA
group were all operated by the same surgeon.

Although various studies have showed promising results with the use of CSWI +
PCA, a widespread implementation of this technique hasn*t been realized. This
could be because of the use of small study groups, which caused underpowered
results on secondary outcomes.
In addition, in some of studies, the control arm didn*t use the current best
practice. For example CEA wasn*t used during the operation or the method of CEA
was without the use of an opioid. Finally, large randomized controlled trials
are lacking that focus on one category of surgical procedures.

Our study will have the overall benefit of analgesic score (OBAS) as primary
endpoint, instead of only the pain score (VAS). The OBAS is a multi-dimensional
quality assessment instrument to measure patients' benefit from postoperative
pain therapy.6 In our opinion the OBAS score is a superior measurement in
comparison to the VAS scoring system to score the true effectiveness of
analgesic therapy. Pain intensity, opioid-related adverse effects and patient
satisfaction are merged at the same time.

Primary Objective: To study whether CSWI+PCA provides similar analgesia after
laparotomies for HPB conditions as compared to PCEA measured as the OBAS score,
a composite endpoint composed of pain score, patient satisfaction and opioid
related side effects.

Secondary Objective(s): To determine whether CSWI+PCA in comparison to PCEA
reduces total operative time.

Other research questions:

- Does CSWI+PCA in comparison to PCEA decrease the length of hospital stay?
- Does CSWI+PCA in comparison to PCEA decrease the occurrence of analgesic
technique failure?
- Does CSWI+PCA in comparison to PCEA decrease the need for rescue medication?
- Does CSWI+PCA in comparison to PCEA decrease the occurrence of hypotension
with the need for additional fluid boluses and noradrenaline dependency?
- Does CSWI+PCA in comparison to PCEA decrease the number of analgesia related
side effects?
- Does CSWI+PCA in comparison to PCEA decrease the usage of indwelling urine
catheters?
- Does CSWI+PCA in comparison to PCEA decrease the length of postoperative ICU
stay?
- Does CSWI+PCA in comparison to PCEA decrease the incidence of post-surgical
pain?
- Does CSWI+PCA in comparison to PCEA reduce the cumulative opioid consumption?
- Does CSWI+PCA in comparison to PCEA decrease the need for CSWI+PCA or PCEA?

This is a randomized controlled, non-inferiority, multicenter trial running in
both AMC and OLVG comparing two treatment strategies.
Patients who will undergo a laparotomy for HPB conditions will be randomly
allocated between A) CSWI+PCA or B) PCEA.

CSWI (Bupivacaine)
After the incision 3x10ml bupivacaine 0.25% is injected at three locations in
the space between peritoneum and posterior fascia. (total 30 ml)

At the end of surgery wound catheters are placed: two in case of a midline
laparotomy, three in case of a right or left subcostal incision.

Catheter positions:
1. Catheter right subcostal region between peritoneum and fascia, tunnelled via
rectus sheath to right thorax
2. Subcostal between rectus sheath and peritoneum on right side, tunnelled to
similar spot on thorax. This catheter and nr 1 covered with foil.
3. Subcostal between rectus sheath and peritoneum on left side with separate
endpoint on skin, rolled and covered with foil.

Each catheter is infused with a bolus of 10ml bupivacaine 0.25% (total 30ml).
Next, with one infuser pump per catheter infusion with bupivacaine 0.125% is
started 4ml/hr. Max 12ml/u over 24hrs.

In case of midline laparotomy only catheter 2 and 3 are used. In case of 2
catheters the two pumps run at 6ml/hr of bupivacaine 0.125%.

PCA (Morphine)
Bolus dose: 1 ml = 1 mg morphine Lock-out time: 5 minutes, 4-uur maximum dose:
30 ml = 30 mg morphine.

3.1.2 Group B (PCEA) (Control arm)
Current best practice of patient controlled epidural analgesia (PCEA).
The PCEA solution consists of bupivacaine (0,125 %) and sufentanil (1 µg/ml).
Running at 6 ml/hr, patients are able to bolus 2ml with a lockout time of 20
minutes.
The 4 hour maximum was set to 1,2 mg bupivacaine/kg.

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness:
- Patients will be receive a telephone call 30 days after surgery. This will
take 5-10 minutes. (see F1)
- The OBAS score is asked standard by the acute pain service.
- Since both techniques (CSWI+PCA and PCEA) are already being used in daily
practice, there is virtually no additional risk involved.