Paravertebral catheter versus Epidural analgesia in Minimally Invasive Esophageal Resection: a randomized controlled multicenter trial (PEPMEN trial)

Esophageal cancer is currently the 9th most common cancer worldwide and is
increasingly diagnosed in the Western world, mainly due to the growing
incidence of adenocarcinoma. Curative treatment for esophageal cancer, which
involves neoadjuvant therapy followed by esophagectomy, is possible for
patients with locally resectable disease without distant metastases.
Esophagectomy is usually performed by a two-stage transthoracic procedure,
which involves an abdominal and a thoracic surgical phase. Open transthoracic
surgery is associated with substantial short-term postoperative thoracic pain,
which can contribute to (pulmonary) complications and delayed recovery.
Thoracic epidural analgesia is the current gold standard for pain control, as
it was shown to be superior to systemic opioids in terms of pain control and
pulmonary complications after open esophagectomy. However, over the last
decades, minimally invasive esophagectomy is increasingly adopted and is
associated with less postoperative pain when compared to open surgery.
Furthermore, enhanced recovery protocols have been introduced and aim at fast
mobilization and recovery after minimally invasive esophagectomy, which may be
hampered by technical failure of analgesia or by hypotensive events due to the
bilateral sympathetic nerve block that is inherent to epidural analgesia. In
this context, a re-evaluation of the current gold standard for pain management
after minimally invasive esophagectomy is warranted.

In a Cochrane review that included a variety of thoracotomy procedures, it was
concluded that paravertebral analgesia provides comparable pain relief while
inducing less postoperative hypotension, urinary retention, and nausea when
compared to epidural analgesia. A systematic review of patients that underwent
esophagectomy indeed reported comparable pain control and less hypotensive
events in retrospective case series that compared paravertebral versus epidural
analgesia, however, the authors highlighted the lack of high-quality
prospective studies and the need to perform such research. In another more
recent retrospective cohort study, paravertebral analgesia was compared to
epidural analgesia in patients undergoing open esophagectomy. That study showed
a 29% reduction in the need for inotropic medication and a 40% shorter mean
length of postoperative admission to the ICU after implementing paravertebral
analgesia. Although these findings are promising, all studies were
retrospective in nature and included patients who underwent esophagectomy by an
open approach, which implies that substantial bias may be present and that the
results may not be applicable to patients undergoing minimally invasive
esophagectomy. Therefore, a randomized controlled trial is required to gain
insight in the efficacy and costs aspects of paravertebral analgesia in
relation to epidural analgesia in patients undergoing minimally invasive
esophagectomy.

To compare paravertebral catheter versus epidural analgesia regarding the
quality of recovery in patients undergoing minimally invasive esophagectomy.

Multicenter, randomized, controlled prospective trial.

Paravertebral catheter analgesia in patients who undergo minimally invasive
esophagectomy.

In contrast to an epidural catheter (control study arm), a paravertebral
catheter (intervention study arm) is placed during the surgical procedure while
the patient is under general anesthesia. This means that the catheterization of
patients in the interventional study arm is certainly not more stressful for
patients. The only potential additional risk of paravertebral catheterization
includes accidental puncturing of the parietal pleura during catheter
placement, which can happen during paravertebral catherization under ultrasound
guidance and sometimes leads to a small pneumothorax (~0.5%). However, in the
current study, paravertebral catheterization is achieved under thoracoscopic
vision. Therefore, this complication has not occurred with the surgical teams
who place the paravertebral catheter under thoracoscopic vision. Hence, the
study procedure is not considered to carry any additional risks when compared
to the standard treatment (epidural analgesia).

The burden of participation for patients is low, as patients will only be asked
to complete additional questionnaires during their postoperative
hospitalization, namely on postoperative days 1-3. The questonnaires involve
the 'Quality of Recovery 40 (QoR-40)' and International Pain Outcomes (IPO)'
lists, as specified in the study protocol under the section 'Secondary study
parameters/endoints'. The additional quality of life questionnaires, which are
described in the study protocol, are already completed by all patients
undergoing esophagectomy in the context of the *Prospective Observational
Cohort study of Oesophageal-gastric cancer Patients (POCOP, www.pocop.nl)'
study. The EORTC C30 and OG-25 questinnaires that are completed for POCOP
before surgery, at 3 months after surgery, and at 6 months after surgery will
also be used for this study.