Pilot study: Targeting the inflammatory response and the induction of acute pain after breast cancer surgery with perioperative infusion of lidocaine

The proposed study addresses an increasing problem in breast cancer treatment:
Pain. Surgery leads to an acute phase response which is characterized by
nociceptive pain and inflammation. Normally there is a recovery of pain and
inflammation and healing occurs. Some patients however, develop excessive
generation of inflammatory response which can lead to hyperalgesia and
eventually to chronic or neuropathic pain. Surgically treated breast cancer
patients have one of the highest incidences of chronic pain (20-68%). Main
contributors to development of chronic pain are severity of postoperative pain
and axillary lymph node dissection (ALND). Mechanisms attributable to the
decline of acute and chronic pain by administering lidocaine intravenously are
thought to be a reduction in discharge of A-delta and C-fibers and a reduction
of misbalance in inflammatory reaction after tissue damage. Lidocaine is a
widely used local anesthetic, known to block sodium channels mostly in acute
pain conditions. However there are indications that intravenous lidocaine also
is effective in the treatment of acute and chronic pain states in low, non
toxic doses We hypothesize that intravenous lidocaine is not only a potential
inhibitor of acute pain, but also acts as an anti-inflammatory agent and
potentially even anti-metastasis in clinically pursuable dosages of
intravenously administered lidocaine Perioperative lidocaine infusion therefore
seems to be an extremely interesting, safe and low cost therapeutic option in
treatment of postoperative pain in breast cancer surgery. Furthermore we
hypothesize that by attenuation of postoperative inflammation a reduction in
postoperative pain and in the development of chronic pain and central
hyperalgesia can be achieved.

We want to answer the following research questions using a peri-operative
infusion of lidocaine (PIL) protocol:
1. Does low dose peri-operative intravenously administered lidocaine attenuate
systemic inflammatory response measured by plasma cytokine levels of
interleukin (IL)-6, IL-8, IL-1beta and IL-1 receptor antagonist (IL-1RA)?
2. Does low dose peri-operative intravenously administered lidocaine attenuate
levels of plasma ICAM-1 after breast surgery?
3. Does low dose peri-operative intravenously administered lidocaine reduce
postoperative pain after breast cancer surgery?

The study is designed as a single centre double blind randomized controlled
clinical trial.
Patients will be included at the pre operative outpatient clinical ward by
anesthesiologists and physician assistants envolved with the research
Patients will supply informed consent before inclusion into the study.
Patients will allow 2 separate blood samples to be drawn.
Patients will use the NRS rating scale to quantify their acute post operative
pain.

The NRS rating scale will be used to assess severity of acute postoperative
pain at 0 and 4 hours postoperatively.

Cytokine and ICAM-1 analysis
Blood will be collected from patients pre- and post-operatively (4 hours) and
will be centrifugated and saved at -80 degrees celcius for cytokine
determination. A Luminex® assay will be used to determine plasma cytokine
levels of IL-6, IL-8, Il-1beta and IL-1RA (Milliplex, Millipore, Billerica, MA).
ICAM-1 concentrations will be determined by enzyme-linked immunosorbent assay
(ELISA).

Anesthesia will be standardized with propofol and sufentanil.
Additional to above regiment patients included in the treatment arm of the
study will receive:
- During induction of anesthesia patients will receive 1,5mg/kg intravenous
lidocaine
- After induction of anesthesia patients will receive 2mg/kg/hr intravenous
lidocaine until 1 hour after the operation has ended. This will be in the
recovery ward where adequate haemodynamic monitoring is available.
Lidocaine concentration used in the study will be Lidocaine 1%

Patients who are not included in the treatment arm of the study will receive
intravenous saline instead of lidocaine in the same timeframe and dosage (
amount of ml received)

The use of lidocaine in this practical research has been proven to be
associated with a low incidence of adverse events. The patients will have to
The patient will have to give a NRS score at 0 and 4 hours after surgery.
The patient will have 1 venous blood sample taken 4 hours after surgery.