SUBLIME study: patient controlled sublingual sufentanil tablets versus intravenous morphine
to enhance the quality of recovery after laparoscopic donor nephrectomy.

Use of the laparoscopic approach for surgical procedures is constantly
increasing. This less invasive method of surgery has proven to be superior with
regard to complication rate, morbidity, postoperative recovery and pain in many
gastro-intestinal , , , hepatobiliary , , splenic , pancreatic , gynaecologic
and urologic surgeries. However, pain management after laparoscopic surgery is
complex. Even though laparoscopy is categorized as a medium-level procedure it
can result in high levels of postoperative pain , complicated to treat because
of its multifactorial origin. Pain after laparoscopy originates from port sites
or retrieval incisions, deep visceral pain from manipulated abdominal organs,
inflammatory pain induced by tissue trauma or pressure related
ischemia-reperfusion injury, or referred pain from distension-induced
neuropraxia of the phrenic nerve . The multiple sources and types of pain after
laparoscopy require a carefully planned multimodal pain management strategy.
Nonetheless, an optimal pain treatment algorithm has not yet been defined.

Postoperative pain is an important influencing factor of recovery and length of
hospital stay. Therefore, further research is needed to explore the best
possible postoperative pain regimen in laparoscopy patients. Compared to open
donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN) is also
associated with less postoperative pain . As a relatively young and healthy
population with little to no comorbidity, voluntary kidney donors constitute a
valuable population for analysis. Pain and wound healing often comprise the
most significant factors of their recovery. Optimising their pain treatment may
enhance recovery and allow for a quicker return to normal daily activities.

The healthPatch® (figure 1a) from MediBioSense is a wearable biosensor that
registers both vital signs and biometric measurements: a single lead ECG, heart
rate variability, respiratory rate, skin temperature, body posture, and number
of steps. The patch is applied to the skin on the left side of the chest and
transfers information wirelessly. Validation studies show reliable measurement
of heart rate (variability) , and ability to accurately monitor the acute
stress response . Therefore, alongside patient reported outcomes, the patch
allows for a subjective measure of pain and mobilization in postoperative
patients at the ward.

Ideally, patients are in control of their own pain management. Studies show
patient controlled analgesia (PCA) leads to lower pain scores and a higher
patient satisfaction . Non-invasive patient controlled analgesia may improve
early mobilisation, as no intravenous line is required . Moreover, non-invasive
patient controlled methods can improve the ease of care for nurses at the ward
. The Zalviso sublingual sufentanil tablet system (SSTS, figure 1b) provides
effective pain management in laparoscopic abdominal and orthopaedic surgery .
As the use of sublingual sufentanil tablets does not require intravenous
access, early mobilization after surgery may be accelerated. Therefore, we
hypothesize that the Zalviso sufentanil sublingual tablet system (SSTS), as
compared to patient controlled intravenous analgesia (PCIA) with morphine,
enhances postoperative mobilization and early quality of recovery after LDN.

To investigate if patient controlled sublingual sufentanil tablets as compared
to patient controlled intravenous morphine lead to improved independent
mobilization on postoperative day 1 after laparoscopic donor nephrectomy (LDN).

A single centre prospective randomized non-blind comparative clinical trial.

Patients will be randomly assigned in a 1:1 fashion to postoperative pain
management with patient controlled sublingual sufentanil tablets or patient
controlled intravenous morphine.

The burden associated with participation in the study is very small. The study
compares two standard of care treatments, efficacy and safety of both
treatments has already been established. If either treatment provides
insufficient pain relief, additional analgesics will be administered. No
invasive measurements will be performed. The HealthPatch® that is applied to
the skin on the chest is small (115 x 40 x 7mm), lightweight (11 grams) and
wireless, and will not interfere with clothing or normal daily activities. The
HealthPatch® does not replace standard monitoring or care in any way.
Assessment of pain, nausea, side effects and complications is part of routine
clinical care. The quality of recovery (QoR-40) questionnaire will take
approximately 10 minutes to complete.