Acute and Chronic Pain Following Modified Radical Mastectomy Clinical Trial
Official title:
Comparison of Oral Lamotrigine Versus Pregabalin for Control of Acute and Chronic Pain Following Modified Radical Mastectomy: Controlled Double-blind Study
Breast cancer is the most frequent neoplastic tumor in women, and surgical treatment is
indicated in most patients. Complications related to this treatment, such as post-mastectomy
pain syndrome (PMPS), a persistent pain that develops after surgery, have been reported.
Although the genesis of the pain is multifactorial, sectioning of the intercostobrachial
nerve is the nerve lesion diagnosed more often (1) ..
Pain relief using drugs with high efficacy provides significant improvement in the patients'
lives. Drugs like lamotrigine (LTG) and gabapentin (GBP) have the ability to overcome the
symptoms of neuropathic pain (4).
Both LTG and PGB have been extensively reviewed in the past for management of painful
neuropathic conditions (5)
This study will be carried out after being approved from the Medical Research Ethics
Committee, faculty of medicine, Assiut University, Assiut, Egypt, and after obtaining written
informed consents from all participating patients.
This prospective randomized clinical study will include ninety female patients with ASA I-II,
aged 18-60 years, have BMI < 30 km\ m2 and scheduled for modified radical mastectomy with
axillary dissection for management of breast cancer.
Excluded from the study are patients with known allergy to the study drugs, significant
cardiac, respiratory, renal, CNS or hepatic disease, drug or alcohol abuse, pregnant women,
patients refusing participation and psychiatric or mental illness that would interfere with
perception and assessment of pain.
According to a random number sequence created by an internet web site (www.random.org),
patients will be randomly assigned to three groups (30 patients each):
Group I: patients will receive oral lamotrigine 100 mg 1 hour before surgery with a sip of
water.
Group II: patients will receive oral pregabalin 150 mg 1 hour before surgery with a sip of
water.
Group III: patients will receive oral placebo 1 hour before surgery with a sip of water.
All patients preoperatively will be instructed in how to evaluate their own pain using NRS
(numerical rating Scale) scored from Zero to ten where 0 = no pain and 10 = the worst pain
imaginable for acute post-operative pain during the first 24 h after operation and LANSS
(Leeds Assessment of Neuropathic Signs and Symptoms) Pain Scale at 3 and 6 months period
after the surgery for chronic post-mastectomy pain assessment.
The LANSS pain scale is a simple bedside test used by the medical community to analyze and
classify pain. It is a, conducted in two parts .i.e. a patient-completed questionnaire and a
brief clinical assessment.
Its purpose is to assess whether the pain experienced is predominantly due to nerve damage or
not. The LANSS scale is the only published tool with validity for discriminating between
neuropathic and nociceptive pain, regardless if the disease-based diagnostic methods. It also
assesses the severity of the pain or its causes.
It is composed of 7 items, five are symptom related and two are examination items.
1. Would you describe your pain as strange unpleasant sensations in your skin? (e.g.
pricking, tingling, pins and needles) - Yes/No
2. Does the skin in the painful areas look different to normal? (e.g. mottled, more
red/pink than usual) - Yes/No
3. Is the skin in the affected area abnormally sensitive to touch? (e.g. unpleasant
sensations if lightly stroked, painful to wear tight clothes) - Yes/No
4. Does your pain come on suddenly in bursts for no apparent reason when you are still?
(e.g. like electric shocks, 'bursting' or 'jumping' sensations) - Yes/No
5. Do you feel that skin temperature in the painful area has changed (e.g. hot, burning) -
Yes/No
6. Does stroking the affected area of skin with a piece of cotton wool produce an
unpleasant painful sensation? - Yes/No
7. Does touching the affected area of skin with a sharp needle feel sharper or duller when
compared to an area of normal skin? - Yes/No Add values in parentheses for sensory
description and examination findings to obtain overall score. TOTAL SCORE (maximum 24)
If score < 12, neuropathic mechanisms are unlikely to be contributing to the patient's
pain.
If score ≥ 12, neuropathic mechanisms are likely to be contributing to the patient's pain.
All patients from the 3 groups will not receive any pre-medications and the anesthetic
technique will be standardized in all groups.
One hour before surgery, the patient will receive one of the study drugs with a sip of water.
On admission to the operative room, patients will be connected to standard monitoring probes
and an I.V. cannula will be inserted and a preload of 500 ml saline will be administered to
all patients.
Pre-oxygenation for 3 minutes with 100% oxygen will be started. Anesthesia will be induced
with 1.5-2 µg/kg fentanyl, 2-3 mg/kg propofol. Endotracheal intubation will be facilitated by
cis-atracurium 0.15 mg/kg. Monitoring will include electoro-cardiography, non-invasive blood
pressure, end tidal CO2 and SaO2. Anesthesia and muscle relaxation will be maintained by
isoflurane 1-1.5 MAC in 50% oxygen/air mixture and cis-atracurium 0.03 mg/kg, respectively At
the end of surgery, muscle relaxation will be reversed by neostagmine 0.5 µg/kg and atropine
0.02µg/kg. Patients will be extubated and transferred to the post-anesthesia care unit
(PACU). In PACU the following data will be recorded: heart rate, mean arterial blood
pressure, respiratory rate and oxygen saturation) at 0h (immediately postoperative), 2h, 4h,
6h, 12h and 24h post-operatively. NRS values at rest (NRS-R) and at movement (NRS-M) with
abduction of ipsilateral arm will be also recorded at the same time points to evaluate acute
postoperative pain.
Rescue post-operative analgesia in the form of I.V. Morphine through Patient controlled
analgesia (PCA) with an initial bolus of 0.1 mg/ kg once pain is expressed followed by 1mg
bolus upon pressing the button by the patient in pain with a lock-out interval of 15 minutes
with no back-ground infusion. The time to first request of rescue analgesia and the total
postoperative (24h) morphine consumption will be observed and recorded.
Postoperative adverse effects such as nausea, vomiting, skin rash, gastric upset and sedation
will be recorded and treated. All patients will be scheduled for two visits into our pain
clinic at the third and the sixth month postoperatively for assessment for the development of
chronic post mastectomy pain using LANSS scale.
Our primary outcome measure is the total amount of rescue morphine received by patients for
24h postoperatively, secondary outcome measures include level of acute postoperative pain by
NRS, the time to first request of rescue analgesia, development of chronic postmastectomy
pain after 3 and 6 months postoperatively.
Sample size is calculated based on previous studies , assuming that a 20% reduction in
postoperative morphine consumption would be clinically relevant , with α = 0.05 and the power
of 0.8 , a samle size of 30 patient in each group will be necessary .
Analysis will perform using SPSS version 17 (Chicago-USA). Data will present as mean ± SD,
numbers, frequencies, and percentages. ANOVA followed by post-hoc test willbe used for
comparison of parametric data. Kruskal Wallis test will use to compare non-parametric data
while Mann-Whitney will be used to compare between two groups. Chi-square test will be used
for comparison between percentages and frequencies. P<0.05 will consider significant.
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